Receptors – Cellular Signalling

In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself.[rx][rx][rx] Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes.[4] Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas). Cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports, or even from cell damage.

Receptors play a key role in cell signaling as they are able to detect chemical signals or physical stimuli. Receptors are generally proteins located on the cell surface or within the interior of the cell such as the cytoplasm, organelles, and nucleus. Cell surface receptors usually bind with extracellular signals (or ligands), which causes a conformational change in the receptor that leads it to initiate enzymic activity, or to open or close ion channel activity. Some receptors do not contain enzymatic or channel-like domains but are instead linked to enzymes or transporters. Other receptors like nuclear receptors have a different mechanism such as changing their DNA binding properties and cellular localization to the nucleus.

Signal transduction begins with the transformation (or transduction) of a signal into a chemical one, which can directly activate an ion channel (ligand-gated ion channel) or initiate a second messenger system cascade that propagates the signal through the cell. Second messenger systems can amplify a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). The downstream effects of these signaling pathways may include additional enzymatic activities such as proteolytic cleavage, phosphorylation, methylation, and ubiquitinylation.

Each cell is programmed to respond to specific extracellular signal molecules,[rx] and is the basis of development, tissue repair, immunity, and homeostasis. Errors in signaling interactions may cause diseases such as cancer, autoimmunity, and diabetes.[rx][rx][rx][rx]

 

GPCRs
GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
ADGRE2
(Adhesion Class GPCRs)
  • regulation of mast cell degranulation (GO:0043304) IMP
ADGRE2 is included in GtoImmuPdb because its tissue expression profile and its ability to activate secretion of inflammatory cytokines (IL-8, TNF) by monocytes and macrophages [265] …
ADGRE5
(Adhesion Class GPCRs)
ADGRE5 is included in GtoImmuPdb because its tissue expression profile and the phenotypes expressed by mouse ADGRE5 knockouts suggest an involvement in inflammation.
ADGRG3
(Adhesion Class GPCRs)
  • B cell differentiation (GO:0030183) ISS
ADGRG3 is expressed by immune cells. It is required for proper B cell development in the spleen [663] …
A2A receptor
(Adenosine receptors)
  • negative regulation of alpha-beta T cell activation (GO:0046636) IEA
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [650] …
A2B receptor
(Adenosine receptors)
  • mast cell degranulation (GO:0043303) IEA
  • positive regulation of mast cell degranulation (GO:0043306) IEA
A2B receptor is discussed in this immuno-oncology review [4] …
A3 receptor
(Adenosine receptors)
Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [650] …
β2-adrenoceptor
(Adrenoceptors)
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [178] …
C3a receptor
(Complement peptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IDA
  • complement receptor activity (GO:0004875) IBA
  • complement component C3a receptor activity (GO:0004876) IDA
Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a.
The complement system plays a critical role intestinal immune homeostasis. In particular, C3 and the C3aR have been identified as being involved in regulating the intestinal immune response during chronic colitis [615,680] …
C5a1 receptor
(Complement peptide receptors)
  • microglial cell activation (GO:0001774) ISS
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
  • complement component C5a receptor activity (GO:0004878) IDA
  • complement component C5a signaling pathway (GO:0038178) IDA
C5aR is typically associated with the compement cascade and innate immunity.
MorphoSys have an anti-C5aR monoclonal antibody (MOR210) in preclinical development as an immuno-oncology agent. The goal of anti-C5aR therapy is to reduce the effects that activation of the C5a/C5aR axis has on promoting cancer cell migration and invasiveness [261,388,451-452] …
C5a2 receptor
(Complement peptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
  • complement component C5a receptor activity (GO:0004878) IBA
C5aR is typically associated with the compement cascade and innate immunity. However, the complement C5a receptor 2 may act as a decoy receptor for C5a, as it has no reported G protein signalling capacity.
CB1 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
CB1 receptor is involved in controlling mast cell degranulation and maturation [609] …
CB2 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [467] …
CCR2
(Chemokine receptors)
  • negative regulation of eosinophil degranulation (GO:0043310) ISS
  • regulation of T cell differentiation (GO:0045580) ISS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) ISS
  • positive regulation of T cell activation (GO:0050870) ISS
CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [4] …
CCR6
(Chemokine receptors)
  • isotype switching to IgA isotypes (GO:0048290) ISS
  • DN2 thymocyte differentiation (GO:1904155) ISS
  • DN3 thymocyte differentiation (GO:1904156) ISS
CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [326,369] …
CCR7
(Chemokine receptors)
  • establishment of T cell polarity (GO:0001768) IC
  • positive regulation of immunological synapse formation (GO:2000522) ISS
  • positive regulation of T cell costimulation (GO:2000525) ISS
  • positive regulation of glycoprotein biosynthetic process involved in immunological synapse formation (GO:2000526) ISS
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR9
(Chemokine receptors)
  • CD8-positive, gamma-delta intraepithelial T cell differentiation (GO:0002305) IEA
CCR9 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Activation of CCR9 by CCL25 plays a key role in leukocyte recruitment to the gut and CCR9 antagonists are being pursued as therapeutic agents for inflammatory bowel disease [681] …
chemerin receptor 1
(Chemerin receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
Studies in CMKLR1 (chemerin receptor 1) knockout mice highlight the role of this receptor in inflammation and obesity. Chemerin receptor 1 is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1. As its name suggests, reslovin E1 is involved in resolving physiological inflammatory responses. The metabolically stable resolvin E1 analogue, RX-10045 (navamepent) has completed Phase 2 clinical trials in several occular inflammation indications. In relation to multiple sclerosis (MS), clinical EAE is significantly reduced in CMKLR1 KO mice. Taking this in to consideration with data that confirm CMKLR1 expression by the main effector cells in MS, this protein is judged to be a novel and tractable target for therapeutic intervention in MS. CMKLR1 antagonists are being pursued as anti-inflammatory agents. The selective CMKLR1 antagonist CCX832 was developed by ChemoCentryx and GlaxoSmithKline as a potential anti-psoriatic medication, but development appears to have halted at Phase 1. is a CMKLR1 antagonist that has shown efficacious effects applicable to MS in vitro and in vivo [227] …
CXCR1
(Chemokine receptors)
CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [4] …
CXCR2
(Chemokine receptors)
  • neutrophil activation (GO:0042119) IDA
CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [4] …
CXCR4
(Chemokine receptors)
CXCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Due to its role in cancer cell homing and metastasis the CXCR4-CXCL12 axis is a potential target for cancer therapy [519,552,657,670] …
CXCR5
(Chemokine receptors)
  • B cell activation (GO:0042113) IEA
CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CX3CR1
(Chemokine receptors)
  • microglial cell activation involved in immune response (GO:0002282) ISS
CX3CR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
EP4 receptor
(Prostanoid receptors)
  • T-helper cell differentiation (GO:0042093) ISS
The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [714] …
FFA2 receptor
(Free fatty acid receptors)
  • cell surface pattern recognition receptor signaling pathway (GO:0002752) IMP
FFAR2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFAR2 (and FFAR3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFAR2 is included in GtoImmuPdb as it is highly expressed on immune cells, in particular neutrophils, and evidence points to a role in diseases with dysfunctional neutrophil responses, such as inflammatory bowel disease (IBD). A Phase 2 trial of the clinical candidate GLPG0974 in ulcerative colitis has been completed (see NCT0182932).
In vitro and in vivo studies suggest that the short-chain fatty acid/FFAR2 axis is modulated by metabolites of cholera toxin, that are produced by gut microbiota, which leads to enhanced mucosal antibody responses against enteric pathogen infection [707] …
FPR1
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
The primary function of FPR1 is recognition of formylpeptides. Detection of bacterial N-formylpeptides via FPR1 activates immune-cell chemotaxis and cytokine release, making this GPCR an important component of the host defense mechanism.

Osei-Owusu et al. (2019) demonstrated that FPR1 on immune cells is the target of the needle cap protein (LcrV; Uniprot accession P0C7U7) of Yersinia pestis (the plague bacterium), via which the bacteria destroy host immune cells [477] …

FPR2/ALX
(Formylpeptide receptors, Leukotriene receptors)
  • microglial cell activation (GO:0001774) ISS
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IDA
  • complement receptor activity (GO:0004875) IBA
Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [660] …
GPR183
(Class A Orphans)
  • B cell activation involved in immune response (GO:0002312) IBA
  • mature B cell differentiation involved in immune response (GO:0002313) ISS
  • positive regulation of B cell proliferation (GO:0030890) IDA
  • T follicular helper cell differentiation (GO:0061470) ISS
Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [314,495] …
GPR84
(Class A Orphans)
GPR84 is proposed as a receptor for free fatty acids. It is predominantly expressed in immune system-related tissues and cells [272] …
MRGPRX2
(Class A Orphans)
  • mast cell degranulation (GO:0043303) IDA
  • mast cell activation (GO:0045576) IDA
Expression of MRGPRX2 was initially reported predominantly in sensory neurons of the dorsal root ganglion. More recently expression has been detected in human mast cells. In these cells the receptor is activated by the antimicrobial peptide LL-37, resulting in calcium mobilisation and degranulation [414,607] …
NK1 receptor
(Tachykinin receptors)
  • positive regulation of lymphocyte proliferation (GO:0050671) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
PAF receptor
(Platelet-activating factor receptor)
  • lipopolysaccharide immune receptor activity (GO:0001875) IEA
  • positive regulation of neutrophil degranulation (GO:0043315) IEA
PAF deficiency results in defective inflammatory response to infection in mice.
PAR2
(Proteinase-activated receptors)
  • T cell activation involved in immune response (GO:0002286) ISS
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IMP
  • negative regulation of toll-like receptor 3 signaling pathway (GO:0034140) IMP
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • neutrophil activation (GO:0042119) IDA
  • positive regulation of eosinophil degranulation (GO:0043311) IDA
PAR2 receptors have been reported to elicit pain and inflammation through a neurogenic mechanism of action, causing release of substance P, activation of NK1 receptors, and sensitization of TRPV1 voltage-gated ion channels. This action can be negated using a selective NK1 receptor antagonist (L732,138) or a TRPV1 receptor antagonist (capsazepine) [210] …
succinate receptor
(Succinate receptor)
  • macrophage activation involved in immune response (GO:0002281) IEA
Succinate acts an an alarmin that triggers the initiation and propagation of danger signals resulting from tissue injury or inflammatory stimuli. It acts through the succinate receptor, SUCNR1. SUCNR1-expressing macrophages release succinate that acts in an autocrine and paracrine feed-forward loop that elevates SUCNR1 expression and leads to enhanced IL-1β production [373] …
Ion Channels
GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
Cav1.4
(Voltage-gated calcium channels (CaV))
Cav1.4 and Cav1.3 are involved in CD8+ T cell survival and cytokine production [473,640] …
Hv1
(Voltage-gated proton channel (Hv1))
Detection of low intracellular pH by the Hv1 ion channel impacts upon the function of B cells, macrophages, neutrophils and microglia [94,640] …
KCa3.1
(Calcium- and sodium-activated potassium channels (KCa, KNa))
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IDA
KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [159,189,408] …
nicotinic acetylcholine receptor α7 subunit
(Nicotinic acetylcholine receptors (nACh))
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [646] …
P2X1
(P2X receptors)
Functional P2X1 receptors are expressed by healthy human eosinophils [693] …
P2X7
(P2X receptors)
  • T cell proliferation (GO:0042098) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [372,522] …
TRPM2
(Transient Receptor Potential channels (TRP))
Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [485] …
TRPV1
(Transient Receptor Potential channels (TRP))
  • microglial cell activation (GO:0001774) IEA
Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [26,57,383,391,550] …

Nuclear Hormone Receptors

GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • toll-like receptor 4 signaling pathway (GO:0034142) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
FXR is predominantly expressed in liver, intestine, kidney and adipose tissue, but has also been detected in immune cells (CD4+, CD8+, CD19+ and CD14+ cells) [559] …
Liver X receptor-α
(1H. Liver X receptor-like receptors)
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • negative regulation of macrophage activation (GO:0043031) ISS
Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [700] …
Peroxisome proliferator-activated receptor-γ
(1C. Peroxisome proliferator-activated receptors)
PPARγ agonists have anti-inflammatory effects. Full PPARγ agonists can cause undesireable weight gain, but partial agonists are devoid of this adverse effect and retain the anti-inflammatory effects of PPARγ modulation.
The PPARγ agonist boosts the inflammatory phenotype of microglia and enhances their phagocytic capacity [349] …
RAR-related orphan receptor-γ
(1F. Retinoic acid-related orphans)
  • T-helper cell differentiation (GO:0042093) ISS
  • T-helper 17 cell differentiation (GO:0072539) ISS
RORγ is a nuclear receptor transcription factor that acts as an immune cell master control switch (most likely associated with expression of the RORγt isoform). This receptor is an essential regulator of type 17 effector T cell differentiation and function. RORγt inhibitors (antagonists and inverse agonists) [147,214,454,588] …

Enzymes

GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
3-phosphoinositide dependent protein kinase 1
(PDK1 family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • regulation of mast cell degranulation (GO:0043304) IEA
In addition to its role in oncology, in mouse studies, PDK1 is reported to play a part in regulating insulin sensitivity (and inhibiting adipose tissue inflammation), via the Pdk1/Foxo1 pathway and expression of Ccr2 [310] …
5-LOX
(Lipoxygenases)
5-LOX is included in GtoImmuPdb because of its involvement in eicosanoid turnover and because it is being actively pursued as a molecular target for the development of novel anti-inflammatory therapeutics [579] …
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of T cell differentiation (GO:0045580) ISS
  • negative regulation of ubiquitin-protein transferase activity (GO:0051444) IDA
  • positive regulation of establishment of T cell polarity (GO:1903905) ISS
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • transitional one stage B cell differentiation (GO:0002333) IEA
  • alpha-beta T cell differentiation (GO:0046632) IEA
  • activated T cell proliferation (GO:0050798) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
  • DN4 thymocyte differentiation (GO:1904157) IEA
Included in GtoImmuPdb based on its association with leukemia.
aconitate decarboxylase 1
(Itaconate biosynthesis)
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [134,167] …
ADAM10
(M12: Astacin/Adamalysin)
  • monocyte activation (GO:0042117) IMP
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of , and regulation of ICOS/ICOSL-dependent immune responses [384] …
ADAM17
(M12: Astacin/Adamalysin)
  • B cell differentiation (GO:0030183) ISS
  • T cell differentiation in thymus (GO:0033077) ISS
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [107] …
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
ADAM8 is reported to drive acute allergen-induced airway inflammation in a mouse model, and effect negated by ADAM8-deficiency (antibody-induced or gene knockout) [491] …
Adenosine deaminase
(Adenosine turnover)
  • T cell activation (GO:0042110) IDA
  • germinal center B cell differentiation (GO:0002314) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • B cell proliferation (GO:0042100) IEA
  • alpha-beta T cell differentiation (GO:0046632) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting …
Aminopeptidase N
(M1: Aminopeptidase N)
Pharmacological inhibitors of APN are being investigated to counter the dysregulated APN expression that has been associated with inflammatory diseases [48,385] …
Arginase I
(Arginase)
  • negative regulation of T cell proliferation (GO:0042130) IDA
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
The role of ARG1 in immuno-oncology is reviewed in [4] …
Arginase II
(Arginase)
  • negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562) IEA
The role of ARG2 in immuno-oncology is reviewed in [4] …
BLK proto-oncogene, Src family tyrosine kinase
(Src family)
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) IBA
  • negative regulation of B cell proliferation (GO:0030889) IBA
  • regulation of mast cell degranulation (GO:0043304) IBA
  • B cell receptor signaling pathway (GO:0050853) IDA
  • regulation of B cell receptor signaling pathway (GO:0050855) IBA
BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [622] …
BMX non-receptor tyrosine kinase
(Tec family)
  • B cell receptor signaling pathway (GO:0050853) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [52] …
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • T cell differentiation in thymus (GO:0033077) IEA
  • CD4-positive, alpha-beta T cell differentiation (GO:0043367) IEA
  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment (GO:0043369) IEA
  • regulation of T cell differentiation (GO:0045580) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
BRAFV600E– immuno-oncology [4] …
Bruton tyrosine kinase
(Tec family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell activation (GO:0042113) TAS
  • positive regulation of B cell differentiation (GO:0045579) TAS
  • B cell receptor signaling pathway (GO:0050853) IDA
  • B cell affinity maturation (GO:0002344) IEA
  • histamine secretion by mast cell (GO:0002553) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [52] …
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • regulation of T cell differentiation in thymus (GO:0033081) TAS
  • myeloid dendritic cell differentiation (GO:0043011) IMP
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [328] …
casein kinase 2, beta polypeptide subunit
(Casein kinase 2 (CK2) family)
CSNK2B is included in Guide to IMMUNOPHARMACOLOGY as it is a subunit of the casein kinase 2 complex.
Caspase 1
(C14: Caspase)
  • pattern recognition receptor signaling pathway (GO:0002221) IC
Caspase 1 is also known as interleukin-1beta (IL-1α) converting enzyme (ICE). Amongst its substrates are the precursors of the inflammatory cytokines IL-1β and IL-18, which it proteolytically cleaves into active mature peptides.
Caspase 3
(C14: Caspase)
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [474] …
Caspase 8
(C14: Caspase)
  • natural killer cell activation (GO:0030101) TAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [394] …
cathepsin B
(C1: Papain)
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin C
(C1: Papain)
  • positive regulation of microglial cell activation (GO:1903980) IEA
Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007).

SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [333] …

cathepsin G
(S1: Chymotrypsin)
  • neutrophil activation (GO:0042119) IDA
  • negative regulation of T cell activation (GO:0050868) IDA
Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin …
cathepsin H
(C1: Papain)
  • immune response-regulating signaling pathway (GO:0002764) IDA
Cathepsin H may act as a pro-granzyme B convertase [146] …
cathepsin L
(C1: Papain)
  • CD4-positive, alpha-beta T cell lineage commitment (GO:0043373) ISS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin S
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [625] …
cereblon
(E3 ubiquitin ligase components)
  • protein ubiquitination (GO:0016567) IMP
Cereblon is a direct molecular target for the immunomodulatory and antiproliferative activities of and its analogues (e.g and ) [25,108,279,381] …
complement factor D
(3.4.21.46 Complement factor D)
A protease component of the alternative complement pathway; responsible for cleaving complement factor B …
component of inhibitor of nuclear factor kappa B kinase complex
(IKK family)
Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [264] …
C-terminal Src kinase
(Csk family)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368) IBA
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [651] …
cyclin dependent kinase 6
(CDK4 subfamily)
  • T cell differentiation in thymus (GO:0033077) IEA
Phenotypic abnormalities in CDK6 knockout mice suggest biological roles in addition to mitotic cell cycle regulation. Alternate roles include involvement in hematopoietic function and inhibition of T cell differentiation [228,489] …
elastase, neutrophil expressed
(S1: Chymotrypsin)
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [632] …
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • T cell activation involved in immune response (GO:0002286) ISS
GCN2 is a so-called ‘stress kinase’. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest.

GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [641] …

FER tyrosine kinase
(Fer family)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) ISS
  • regulation of mast cell degranulation (GO:0043304) IBA
FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS …
FGR proto-oncogene, Src family tyrosine kinase
(Src family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
  • negative regulation of natural killer cell activation (GO:0032815) IEA
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [44] …
FKBP prolyl isomerase 1A
(Peptidyl-prolyl cis/trans isomerases)
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • T cell activation (GO:0042110) NAS
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) IDA
  • protein ubiquitination (GO:0016567) IEA
  • negative regulation of protein ubiquitination (GO:0031397) IEA
  • activated T cell proliferation (GO:0050798) IEA
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [483] …
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation.

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [23] …

HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • innate immune response-activating signaling pathway (GO:0002758) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [44] …
heparanase
(3.2.1.- Glycosidases)
Heparanase has been studied as a novel drug target associated with the immune response and inflammation [112-113] …
histone deacetylase 3
(3.5.1.- Histone deacetylases (HDACs))
  • positive regulation of protein ubiquitination (GO:0031398) ISS
A 2017 study reports that HDAC3 (more so than HDACs -6, -1/2, or -8) regulates inflammatory gene expression in rheumatoid arthritis fibroblast-like synoviocytes, and is required for type I IFN production [20] …
histone deacetylase 6
(3.5.1.- Histone deacetylases (HDACs))
  • protein polyubiquitination (GO:0000209) IEA
Accumulating evidence indicates that non-selective HDAC inhibitors exhibit immunosuppressive/anti-inflammatory activity in vitro and in vivo, and have potential as a drug class with uses in immune and inflammatory diseases [46,186,526,541,575] …
IL2 inducible T cell kinase
(Tec family)
  • NK T cell differentiation (GO:0001865) IBA
  • T cell activation (GO:0042110) TAS
  • gamma-delta T cell activation (GO:0046629) ISS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) IBA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [52] …
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • T cell proliferation (GO:0042098) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
The indoleamine 2,3 dioxygenase (IDO) branch of the kynurenine (KYN) pathway of tryptophan metabolism has been intensely studied in relation to immune tolerance and allergy. IDO is generally considered to be a tolerogenic, immunosuppressive enzyme, that is induced by IFN-γ. It provides a negative feedback pathway that limits uncontrolled immune responses. Its immunosuppressive actions arise from its promotion of tryptophan depletion, and elevation of KYN metabolite levels. The aryl hydrocarbon receptor serves as a receptor for KYN and should be considered when evaluating the IDO-KYN pathway in immune homeostasis and its potential to modulate innate and adaptive immune responses [327] …
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [49,66,585] …
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons …
INPP5D
(Inositol polyphosphate phosphatases)
  • positive regulation of B cell differentiation (GO:0045579) IBA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • negative regulation of B cell proliferation (GO:0030889) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [450,601] …
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 2 signaling pathway (GO:0034134) IMP
  • toll-like receptor 4 signaling pathway (GO:0034142) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
interleukin 1 receptor associated kinase 2
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
IRAK2 is one of the proximal mediators of IL-1 signalling via the IL-1 receptor, the other being IRAK1. It plays a part in IL-1-induced upregulation of the transcription factor NF-κB. IRAK2 interacts with TRAF6 and Myd88.
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
IRAK4 is essential for most innate immune responses to bacteria and viruses, and IRAK4 deficiency (caused by mutations) has been shown to result in recurrent invasive pneumococcal disease [416] …
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • positive thymic T cell selection (GO:0045059) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
IP3 kinase B (ITPKB) as an essential mediator of T cell activation, whose inhibition is considered a novel approach to treat autoimmune disease [421] …
Janus kinase 2
(Janus kinase (JakA) family)
  • microglial cell activation (GO:0001774) ISS
  • positive regulation of natural killer cell proliferation (GO:0032819) IDA
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of NK T cell proliferation (GO:0051142) IDA
JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [59,61,597] …
Janus kinase 3
(Janus kinase (JakA) family)
  • B cell differentiation (GO:0030183) ISS
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
  • negative regulation of T cell activation (GO:0050868) ISS
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [16] …
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell differentiation (GO:0030217) IMP
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway (GO:0038094) IDA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) NAS
  • positive regulation of T cell activation (GO:0050870) IDA
  • regulation of lymphocyte activation (GO:0051249) NAS
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [483] …
Leukotriene A4 hydrolase
(Leukotriene and lipoxin metabolism, M1: Aminopeptidase N, Hydrolases)
LTA4H is an established immunomodulatory target. LTA4H exhibits opposing pro- and anti-inflammatory functions: epoxide hydrolase (EH) activity which catalyses the hydrolysis of leukotriene A4 to leukotriene B4, which promotes neutrophilic inflammation, and aminopeptidase (AP) activity which catalyses the hydrolysis of the tripeptide proline-glycine-proline (PGP) to promote resolution of neutrophilic infiltration.

Expression has been identified in some cancer cells, where it may play a role in the development and progression of cancers associated with chronic inflammation, suggesting that LTA4H inhibitors may have efficacy as anti-cancer therapeutics [119] …

LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) ISS
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) ISS
  • Fc receptor mediated inhibitory signaling pathway (GO:0002774) ISS
  • negative regulation of B cell proliferation (GO:0030889) IBA
  • T cell costimulation (GO:0031295) TAS
  • regulation of mast cell activation (GO:0033003) ISS
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of mast cell degranulation (GO:0043304) ISS
  • regulation of B cell receptor signaling pathway (GO:0050855) ISS
  • histamine secretion by mast cell (GO:0002553) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
  • positive regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060369) IEA
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [196,208,631] …
misshapen like kinase 1
(MSN subfamily)
MINK promotes the negative selection of autoreactive thymocytes during T cell development, an action that is effected by JNK-mediated apoptosis [412] …
mitogen-activated protein kinase 1
(ERK subfamily)
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [319,389] …
mitogen-activated protein kinase 14
(p38 subfamily)
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [234-235,352,492,516,668] …
mitogen-activated protein kinase 8
(JNK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
By regulating AP-1 transcriptional activity in response to cytokine activation, JNK1 contributes to the production of immunomodulators such as RANTES, IL-8 and GM-CSF .
mitogen-activated protein kinase 9
(JNK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of protein ubiquitination (GO:0031398) IEA
Experimental evidence suggests that JNK2 is important in T-cell differentiation [284,545,606,704] …
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • cytosolic pattern recognition receptor signaling pathway (GO:0002753) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [148,548] …
mitogen-activated protein kinase kinase kinase 8
(STE-unique family)
  • T cell costimulation (GO:0031295) TAS
MAP3K8 (a.k.a. TPL2) is the primary regulator of ERK-mediated gene transcription downstream of multiple proinflammatory stimuli [207,698] …
MMP14
(M10: Matrix metallopeptidase)
  • positive regulation of B cell differentiation (GO:0045579) ISS
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [161] …
MMP8
(M10: Matrix metallopeptidase)
  • regulation of microglial cell activation (GO:1903978) TAS
  • positive regulation of microglial cell activation (GO:1903980) ISS
MMP8 is included in GtoImmuPdb based on its potential protective role in asthma.
MMP9
(M10: Matrix metallopeptidase)
Mucosal up-regulation of MMP-9 correlates with the severity of inflammation in ulcerative colitis, and may be responsible for the mucosal damage in active ulcerative colitis [344] …
myeloperoxidase
(1.-.-.- Oxidoreductases)
Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme whose peroxidase enzymatic activity generates hypohalous acids that constitute the major component responsible for neutrophil antimicrobial activity, and as such MPO participates in the innate immune defense mechanism. Since the discovery that MPO-derived oxidants contribute towards the propagation of inflammatory diseases (including cystic fibrosis, chronic obstructive pulmonary disease, Parkinson’s disease, rheumatoid arthritis, acute kidney injury, atherosclerosis and cardiovascular disease) [325,458] …
otulin
(C101: OTULIN peptidase)
  • protein ubiquitination (GO:0016567) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IMP
Otulin is reported as a negative regulator of inflammation and autoimmunity [150] …
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
PAK1 is reported to modulate a pro-inflammatory PPARγ/NF-κB cascade in intestinal inflammation, that may be relevant in inflammatory bowel disease and colitis-associated cancer [151] …
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [463] …
peptidylprolyl isomerase A
(Peptidyl-prolyl cis/trans isomerases)
  • negative regulation of protein K48-linked ubiquitination (GO:0061944) IMP
Cyclophilin A (CypA) is well known as a specific binding protein for cyclosporin A (CsA) [238] …
phosphatase and tensin homolog
(Lipid phosphate phosphatases)
  • positive regulation of ubiquitin protein ligase activity (GO:1904668) IDA
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • T cell proliferation (GO:0042098) IEA
  • B cell proliferation (GO:0042100) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
Accumulating evidence suggests that loss-of-function mutations or deletion of PTEN is an immune evasion mechanism exploited by tumour cells [598] …
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PI3Kα is primarily recognised for its oncogenic function. We have included it in GtoImmuPdb based on its numerous GO immune process associations.
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • natural killer cell differentiation (GO:0001779) TAS
  • natural killer cell activation (GO:0030101) TAS
  • B cell differentiation (GO:0030183) IC
  • T cell differentiation (GO:0030217) TAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • mast cell degranulation (GO:0043303) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) TAS
PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [244] …
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • T cell proliferation (GO:0042098) TAS
  • T cell activation (GO:0042110) TAS
  • mast cell degranulation (GO:0043303) TAS
The role of PI3Kγ in immuno-oncology is reviewed in [4] …
phosphodiesterase 4B
(Phosphodiesterases, 3′,5′-cyclic nucleotide (PDEs))
  • T cell receptor signaling pathway (GO:0050852) IMP
PDE4 is a drug target, whose inhibition has anti-inflammatory action. PDE4 inhibitors have already entered clinical use, being employed in the treatment of inflammatory skin conditions such as psoriatic arthritis () and atopic dermatitis (). PDE4B is the predominant phosphodiesterase subtype in monocytes and neutrophils and this is thought to be the sub-type central to inflammatory action of phosphodiesterases [664] …
phosphodiesterase 4D
(Phosphodiesterases, 3′,5′-cyclic nucleotide (PDEs))
  • T cell receptor signaling pathway (GO:0050852) IMP
The selective PDE4 inhibitor (OPA-15406) has been shown to inhibit PDE4D3 [468] …
phosphodiesterase 5A
(Phosphodiesterases, 3′,5′-cyclic nucleotide (PDEs))
  • T cell proliferation (GO:0042098) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
The role of PDE5A in immuno-oncology is reviewed in [4] …
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • B cell differentiation (GO:0030183) IC
  • T cell differentiation (GO:0030217) IC
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [386] …
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [219,547] …
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) ISS
  • toll-like receptor signaling pathway (GO:0002224) ISS
  • macrophage activation involved in immune response (GO:0002281) ISS
  • B cell differentiation (GO:0030183) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) IDA
  • follicular B cell differentiation (GO:0002316) IEA
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [219,547] …
proteasome 20S subunit beta 8
(T1: Proteasome)
PSMB8 is a component of the immunoproteasome [188] …
proteinase 3
(S1: Chymotrypsin)
Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [332] …
protein kinase C beta
(Alpha subfamily)
  • B cell activation (GO:0042113) ISS
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) ISS
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • neutrophil activation (GO:0042119) IDA
  • B cell proliferation (GO:0042100) IEA
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C epsilon
(Eta subfamily)
  • TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669) ISS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • macrophage activation involved in immune response (GO:0002281) IEA
  • negative regulation of protein ubiquitination (GO:0031397) IEA
PKCε is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C eta
(Eta subfamily)
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IMP
PKCη is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C gamma
(Alpha subfamily)
  • negative regulation of protein ubiquitination (GO:0031397) IDA
PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
  • CD4-positive, alpha-beta T cell proliferation (GO:0035739) IEA
  • positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563) IEA
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [32] …
protein kinase C zeta
(Iota subfamily)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase, DNA-activated, catalytic subunit
(Other PIKK family kinases)
  • positive regulation of lymphocyte differentiation (GO:0045621) ISS
  • B cell lineage commitment (GO:0002326) IEA
  • immature B cell differentiation (GO:0002327) IEA
  • T cell lineage commitment (GO:0002360) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • T cell receptor V(D)J recombination (GO:0033153) IEA
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc …
protein kinase N1
(Protein kinase N (PKN) family)
  • negative regulation of B cell proliferation (GO:0030889) IEA
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [242] …
protein tyrosine kinase 2
(Fak family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [114] …
protein tyrosine kinase 2 beta
(Fak family)
  • marginal zone B cell differentiation (GO:0002315) ISS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific (e.g. chemokine and integrin receptors) T cell development and activation [114] …
protein tyrosine phosphatase non-receptor type 22
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • T cell differentiation (GO:0030217) ISS
  • regulation of natural killer cell proliferation (GO:0032817) IDA
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IMP
  • positive regulation of toll-like receptor 7 signaling pathway (GO:0034157) IBA
  • positive regulation of toll-like receptor 9 signaling pathway (GO:0034165) IBA
  • T cell receptor signaling pathway (GO:0050852) IBA
  • regulation of B cell receptor signaling pathway (GO:0050855) NAS
  • negative regulation of T cell receptor signaling pathway (GO:0050860) IDA
  • negative regulation of T cell activation (GO:0050868) IMP
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070433) IMP
  • positive regulation of protein K63-linked ubiquitination (GO:1902523) IMP
  • positive regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000566) IBA
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [132] …
RAB27A, member RAS oncogene family
(RAB subfamily)
  • cytotoxic T cell degranulation (GO:0043316) IEA
  • natural killer cell degranulation (GO:0043320) IEA
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [296] …
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [447,529,577,656] …
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of protein ubiquitination (GO:0031398) IMP
  • toll-like receptor 2 signaling pathway (GO:0034134) IDA
  • T cell receptor signaling pathway (GO:0050852) ISS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • immature T cell proliferation in thymus (GO:0033080) IEA
  • positive regulation of immature T cell proliferation in thymus (GO:0033092) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • CD4-positive, alpha-beta T cell proliferation (GO:0035739) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IEA
  • nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427) IEA
  • positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563) IEA
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [461] …
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • T cell differentiation in thymus (GO:0033077) ISS
  • regulation of activated T cell proliferation (GO:0046006) ISS
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [447,529,577,656] …
serine/threonine kinase 11
(LKB subfamily)
  • positive thymic T cell selection (GO:0045059) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
Development of fatal TH2-dominant inflammatory symptoms in mice with a specific Stk11 knockout in their Treg cells, and experiments showing Stk11’s role in the coordination of metabolic and functional fitness of Treg cells, suggest that this kinase acts as a crucial checkpoint that actively maintains Treg cell survival and homeostatic function [247,706] …
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • protein ubiquitination (GO:0016567) IDA
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [123] …
sphingosine kinase 1
(Sphingosine kinase)
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • regulation of microglial cell activation (GO:1903978) ISS
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [557-558] …
sphingosine kinase 2
(Sphingosine kinase)
  • positive regulation of mast cell activation involved in immune response (GO:0033008) ISS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling, and is considered to be an anti-inflammatory enzyme with potential druggability for the treatment of autoimmune and inflammatory diseases [514] …
spleen associated tyrosine kinase
(Syk family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) ISS
  • macrophage activation involved in immune response (GO:0002281) ISS
  • neutrophil activation involved in immune response (GO:0002283) ISS
  • leukocyte activation involved in immune response (GO:0002366) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IBA
  • regulation of neutrophil degranulation (GO:0043313) ISS
  • positive regulation of B cell differentiation (GO:0045579) IMP
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IBA
  • B cell receptor signaling pathway (GO:0050853) IMP
  • B cell differentiation (GO:0030183) IEA
  • gamma-delta T cell differentiation (GO:0042492) IEA
  • mast cell degranulation (GO:0043303) IEA
  • beta selection (GO:0043366) IEA
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [217,527] …
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [382] …
TANK binding kinase 1
(IKK family)
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [308] …
tec protein tyrosine kinase
(Tec family)
  • T cell receptor signaling pathway (GO:0050852) IBA
  • B cell receptor signaling pathway (GO:0050853) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [52] …
tripartite motif containing 21
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • protein polyubiquitination (GO:0000209) IDA
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • protein monoubiquitination (GO:0006513) IDA
  • protein ubiquitination (GO:0016567) IDA
  • protein autoubiquitination (GO:0051865) IDA
  • ubiquitin protein ligase activity (GO:0061630) IDA
  • protein K63-linked ubiquitination (GO:0070534) IMP
Tripartite motif-containing (TRIM) superfamily proteins are critical in a variety of biological processes in innate immunity and are important for eradication of invading pathogens [479,517,653] …
tripartite motif containing 38
(2.3.2.27 RING-type E3 ubiquitin transferase)
  • protein polyubiquitination (GO:0000209) IBA
  • protein ubiquitination (GO:0016567) IBA
  • ubiquitin protein ligase activity (GO:0061630) ISS
  • protein K48-linked ubiquitination (GO:0070936) IEA
TRIM38 catalyses the ubiquitination of Lys48 of the Toll-like receptor (TLR) adaptor protein TICAM1 (commonly referred to as TRIF) which mediates its proteosomal degradation. This action has been shown to inhibit TLR3-driven type I interferon signaling of the innate immune response [701] …
TXK tyrosine kinase
(Tec family)
  • T cell receptor signaling pathway (GO:0050852) ISS
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [52] …
vanin 1
(Hydrolases)
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [614] …
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
zeta chain of T cell receptor associated protein kinase 70
(Syk family)
  • T cell differentiation (GO:0030217) NAS
  • T cell activation (GO:0042110) TAS
  • B cell activation (GO:0042113) TAS
  • positive thymic T cell selection (GO:0045059) IDA
  • positive regulation of T cell differentiation (GO:0045582) IDA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • beta selection (GO:0043366) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [27] …
Catalytic Receptors
GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IBA
  • positive regulation of natural killer cell differentiation (GO:0032825) IDA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [233] …
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) IBA
  • T cell costimulation (GO:0031295) IBA
  • B cell costimulation (GO:0031296) IBA
  • positive regulation of T cell proliferation (GO:0042102) IBA
This is a type III membrane bound receptor for B cell activating factor (BAFF). BAFF enhances B cell survival and hence regulates the peripheral B cell population. It is suggested that overproduction of BAFF may enhance the survival of autoreactive B cells, an effect which may contribute in the path …
CD27
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell differentiation (GO:0045579) NAS
  • positive regulation of T cell differentiation (GO:0045582) IEA
CD27 (TNFRSF7) is a co-stimulatory immune checkpoint molecule that is expressed on various immune cells, including T cells and NK (natural killer) cells. The endogenous ligand for CD27 is CD70. CD27 interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1). It has been recognized as playing an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T cell) adaptive immune response. CD27 is an immuno-oncology target [82,642] …
CD40
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IBA
  • positive regulation of B cell proliferation (GO:0030890) IBA
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) IBA
  • B cell proliferation (GO:0042100) NAS
  • B cell activation (GO:0042113) IBA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IBA
CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C …
Cytokine receptor-like factor 2
(IL-2 receptor family)
  • positive regulation of mast cell activation (GO:0033005) IMP
Cytokine receptor-like factor 2 is the signal transducing subunit of the functional heterodimeric receptor for thymic stromal lymphopoietin (TSLP). Ligand binding is attributed to the interleukin-7 receptor subunit α.
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of B cell proliferation (GO:0030889) ISS
  • negative regulation of T cell proliferation (GO:0042130) ISS
  • T cell receptor signaling pathway (GO:0050852) ISS
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways.
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • RIG-I signaling pathway (GO:0039529) IDA
RIG-I is an intracellular sensor that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of the type I interferon response [406] …
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of MDA-5 signaling pathway (GO:0039534) IMP
  • negative regulation of RIG-I signaling pathway (GO:0039536) IDA
  • positive regulation of MDA-5 signaling pathway (GO:1900245) ISS
  • positive regulation of RIG-I signaling pathway (GO:1900246) ISS
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA.
Fas
(Tumour necrosis factor (TNF) receptor family)
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L, generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or CD95L develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [616] …
Fc fragment of IgE receptor Ia
(Fc epsilon receptors)
The product of the FCεR1A gene is a single-pass type I membrane protein that is a high-affinity receptor for immunoglobulin E (IgE). It is the ligand binding subunit of the tetrameric FCεRI, exhibiting a Kd of ~0.1nM.
Fc fragment of IgE receptor Ig
(Fc epsilon receptors)
  • neutrophil activation involved in immune response (GO:0002283) IBA
  • T cell differentiation involved in immune response (GO:0002292) IBA
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) IBA
  • IgE receptor activity (GO:0019767) IBA
  • Fc-gamma receptor signaling pathway (GO:0038094) IBA
  • Fc-epsilon receptor signaling pathway (GO:0038095) IMP
The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors.
fms related receptor tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • B cell differentiation (GO:0030183) ISS
  • lymphocyte proliferation (GO:0046651) ISS
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib.
Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [490] …
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
GITR appears to act as a co-stimulatory immune checkpoint molecule. T cell activation induces GITR expression. GITR inhibits the suppressive activity of Treg cells and promotes survival of Teff cells.
herpes virus entry mediator
(Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family)
  • T cell costimulation (GO:0031295) IDA
  • negative regulation of alpha-beta T cell proliferation (GO:0046642) IBA
HSV viral envelope glycoprotein D (gD) binds to this protein and thereby gains entry to the cell. HVEM binds to several TRAFadaptor proteins to mediate intracellular signalling and activation of the immune response.
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
(Integrins)
  • B cell differentiation (GO:0030183) IC
Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [236] …
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291) IMP
ITGAL associates with the beta 2 chain (ITGB2) integrin and CD18 to form the lymphocyte function-associated antigen-1 (LFA-1) complex. LFA-1 is crucial for leukocyte intercellular adhesion and costimulatory signaling in the immune system. Ligands for LFA-1 are the intercellular adhesion molecules (ICAMs) 1-3. ITGAL is the target of the withdrawn psoriasis monoclonal antibody drug efalizumab …
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit)
(Integrins)
  • microglial cell activation (GO:0001774) NAS
  • positive regulation of neutrophil degranulation (GO:0043315) IGI
ITGB2 is the beta component of the β2 integrins. It forms αβ heterodimers with the CD11 alpha subunits ITGAL (αL aka CD11a forming integrin LFA-1), ITGAM (αM aka CD11b, forming integrin Mac-1) and ITGAX (αX aka CD11c, forming integrin p150/95). Beta2-integrins are essential for leukocyte extravasation to sites of infection (i.e. leukocyte trafficking), and other immunological processes including neutrophil phagocytosis and ROS production, and T cell activation. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [323] …
interferon α/β receptor 1
(Interferon receptor family)
IFNAR1 is a subunit of the functional receptor for type I interferons (NOT interferon γ). Type I interferons (IFN) exhibit an established anti-viral action. However, type I IFN signalling also appears to play a role in impaired resistance to a range of other pathogens (e.g. bacterial infection) [98,448] …
Interferon γ receptor 1
(Interferon receptor family)
  • microglial cell activation (GO:0001774) ISS
A subunit of the functional receptor for interferon γ.
interferon induced with helicase C domain 1
(RIG-I-like receptor family)
  • MDA-5 signaling pathway (GO:0039530) IDA
MDA5 is an intracellualar RNA sensor. It recognizes longer double-stranded RNA sequences than RIG-1. In autoimmunity, MDA5 has been specifically linked with type I diabetes and anti-MDA5 autoantibodies can be detected in patients with certain connective tissue autoimmune conditions [7,258,420] …
Interleukin-11 receptor, α subunit
(IL-6 receptor family)
This is the ligand-binding component of the functional receptor for interleukin 11.
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of natural killer cell proliferation (GO:0032819) IDA
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IDA
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of NK T cell proliferation (GO:0051142) IDA
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Interleukin 13 receptor, α2 acts as a high affinity decoy receptor for interleukin 13 that sequesters the ligand away from IL13Rα1 and is involved in down-regulating IL-13 responses in vivo. IL13ra2 null mice exhibit enhanced IL-13 responses [692] …
Interleukin-15 receptor subunit α
(IL-2 receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
  • positive regulation of natural killer cell differentiation (GO:0032825) IEA
This is the ligand binding subunit of the functional IL-15 receptor complex.
Interleukin-18 receptor 1
(Immunoglobulin-like family of IL-1 receptors)
  • natural killer cell activation (GO:0030101) IEA
  • T-helper 1 cell differentiation (GO:0045063) IEA
Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of macrophage activation (GO:0043032) IEA
IL1RL1 (ST2) is the ligand binding subunit of the functional receptor for IL-33. It is mainly expressed on mast cells, eosinophils and other immune cells [206] …
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T cell differentiation (GO:0045582) IEA
Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36.

An antibody that mimics IL-36RA’s antagonist activity at the IL-36 receptor (MAB92) has been described [205] …

Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • immune response-inhibiting signal transduction (GO:0002765) IEA
  • T cell proliferation (GO:0042098) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24.
Interleukin 21 receptor
(IL-2 receptor family)
  • natural killer cell activation (GO:0030101) NAS
This is the ligand binding subunit of the functional heterodimeric receptor for interleukin 21.
Interleukin 23 receptor
(IL-12 receptor family)
  • positive regulation of natural killer cell proliferation (GO:0032819) IC
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IC
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • positive regulation of NK T cell activation (GO:0051135) IC
  • positive regulation of NK T cell proliferation (GO:0051142) IC
  • positive regulation of T-helper 17 cell lineage commitment (GO:2000330) ISS
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • positive regulation of activated T cell proliferation (GO:0042104) IBA
  • regulation of isotype switching to IgG isotypes (GO:0048302) IEA
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit).
Interleukin-2 receptor subunit α
(IL-2 receptor family)
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • regulation of T cell homeostatic proliferation (GO:0046013) IEA
  • activated T cell proliferation (GO:0050798) IEA
  • regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000561) IEA
IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab. Another anti-CD25 mAb, inolimomab, has received orphan drug designation from the EMA, for the treatment of graft-versus-host disease. Phase 3 findings for this drug and indication are reported in [583] …
Interleukin-2 receptor subunit β
(IL-2 receptor family)
  • natural killer cell activation (GO:0030101) IBA
IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R.
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • mature B cell differentiation (GO:0002335) IEA
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0002361) IEA
  • positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0032831) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • positive regulation of B cell differentiation (GO:0045579) IEA
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor.
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • negative regulation of macrophage activation (GO:0043031) NAS
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of mast cell degranulation (GO:0043306) IEA
  • T-helper 1 cell differentiation (GO:0045063) IEA
  • T-helper 2 cell differentiation (GO:0045064) IEA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) IEA
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [250] …
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • T-helper 17 cell lineage commitment (GO:0072540) IEA
IL6R polymorphisms are associated with asthma risk [187] …
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of T cell proliferation (GO:0042102) IMP
This is the common signal transducing subunit shared by members of the IL-6 family of cytokine receptors [538] …
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • T cell differentiation in thymus (GO:0033077) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • B cell proliferation (GO:0042100) IEA
This is the ligand binding subunit of the functional IL-7 receptor complex.
Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [507] …
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • immature B cell differentiation (GO:0002327) ISS
  • B cell differentiation (GO:0030183) IBA
  • T cell differentiation (GO:0030217) ISS
  • Fc receptor signaling pathway (GO:0038093) IDA
  • mast cell degranulation (GO:0043303) IMP
Stem cell factor (SCF) and its receptor KIT (c-KIT) play an essential part in mast cell biology. In addition to CSF/KIT-mediated regulation of mast cell development, proliferation and survival, KIT is also reported to be involved in the adhesion of mast cells to human airway epithelial cells (a homing and adhesion role), suggesting a mechanism that could be targeted for anti-asthmatic potential [226] …
lymphotoxin β receptor
(Tumour necrosis factor (TNF) receptor family)
  • myeloid dendritic cell differentiation (GO:0043011) IEA
Interaction of the lymphotoxin β receptor (LTBR) with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [111] …
membrane spanning 4-domains A2
(Fc epsilon receptors)
  • Fc-epsilon receptor signaling pathway (GO:0038095) IEA
The protein product of the MS4A2 gene is the β subunit of the FCεRI. It has commonly known as FCER1B. The IgE-receptor (FCεRI), is a tetramer composed of an α, β, and 2 disulfide-linked γ chains expressed on the surface of mast cells and basophils that is crucial for mediating the allergic response. It has been suggested that cytoplasmic FCER1B that is not associated with FCεRI complexes may act as a negative regulator of the signalling pathway to degranulation by sequestering important signalling partners such as the Lyn tyrosine kinase [470] …
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • natural killer cell differentiation (GO:0001779) IEA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [50,659] …
NLRC3
(NOD-like receptor family)
  • T cell activation (GO:0042110) IEP
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [396,731] …
NLRP3
(NOD-like receptor family)
  • pattern recognition receptor signaling pathway (GO:0002221) IC
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as , and [34,397] …
NLRP6
(NOD-like receptor family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) …
NLRX1
(NOD-like receptor family)
  • negative regulation of RIG-I signaling pathway (GO:0039536) IEA
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections.
nucleotide binding oligomerization domain containing 1
(NOD-like receptor family)
  • pattern recognition receptor signaling pathway (GO:0002221) IDA
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ …

nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • pattern recognition receptor signaling pathway (GO:0002221) IDA
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
  • positive regulation of B cell activation (GO:0050871) IDA
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • positive regulation of protein K63-linked ubiquitination (GO:1902523) IMP
  • toll-like receptor 2 signaling pathway (GO:0034134) IEA
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) IEA
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).

Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major …

OX40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) ISS
  • T cell proliferation (GO:0042098) ISS
The OX40/OX40L pair is involved in late T-cell costimulatory signalling and both are transiently expressed following antigen recognition. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [676] …
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • natural killer cell differentiation (GO:0001779) ISS
  • B cell differentiation (GO:0030183) ISS
  • T cell differentiation (GO:0030217) ISS
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell proliferation (GO:0042100) ISS
  • positive regulation of T cell proliferation (GO:0042102) ISS
  • T cell activation (GO:0042110) TAS
  • T cell receptor signaling pathway (GO:0050852) IDA
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of antigen receptor-mediated signaling pathway (GO:0050857) ISS
  • negative regulation of microglial cell activation (GO:1903979) TAS
  • DN2 thymocyte differentiation (GO:1904155) TAS
  • positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis (GO:1905451) ISS
  • gamma-delta T cell differentiation (GO:0042492) IEA
  • positive thymic T cell selection (GO:0045059) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • alpha-beta T cell proliferation (GO:0046633) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
CD45 is a high molecular weight cell surface glycoprotein expressed by cells of hematopoietic origin. Alternate transcripts lead to expression of isoforms that differ in their extracellular (ligand binding) domain (potentially facilitating differential and/or cell type specific biological functions [149] …
TACI
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of B cell proliferation (GO:0030889) IBA
TACI is a lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can underlie immunodeficiencies and autoimmune diseases. TACI ligands are molecular targets of approved and investigational biologics that are …
TLR1
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IDA
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IGI
  • macrophage activation (GO:0042116) NAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 1 signaling pathway (GO:0034130) IEA
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [638] …
TLR10
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 10 signaling pathway (GO:0034166) IEA
To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [475] …
TLR2
(Toll-like receptor family)
  • lipopolysaccharide immune receptor activity (GO:0001875) TAS
  • toll-like receptor signaling pathway (GO:0002224) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) IDA
  • microglial cell activation (GO:0001774) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 2 signaling pathway (GO:0034134) IEA
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [440] …
TLR3
(Toll-like receptor family)
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • microglial cell activation (GO:0001774) IEA
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) IEA
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
TLR3 is an endosomal anti-viral receptor [638] …
TLR4
(Toll-like receptor family)
  • lipopolysaccharide immune receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) IDA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IDA
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) ISS
  • macrophage activation (GO:0042116) IMP
  • positive regulation of macrophage activation (GO:0043032) ISS
  • B cell proliferation involved in immune response (GO:0002322) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430) IEA
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [62,508] …
TLR5
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 5 signaling pathway (GO:0034146) IEA
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [419] …
TLR6
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IDA
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) IGI
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) ISS
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) IDA
  • positive regulation of macrophage activation (GO:0043032) ISS
  • toll-like receptor 6 signaling pathway (GO:0034150) IEA
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides (LP) from bacterial cell membranes, and effect an immune response [183] …
TLR7
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • toll-like receptor 7 signaling pathway (GO:0034154) IBA
TLR7 is an endosomal receptor detecting ssRNA [638] …
TLR8
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • toll-like receptor 8 signaling pathway (GO:0034158) IDA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
TLR8 is an endosomal receptor detecting ssRNA [638] …
TLR9
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • positive regulation of B cell proliferation (GO:0030890) IDA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • regulation of toll-like receptor 9 signaling pathway (GO:0034163) IDA
  • regulation of B cell differentiation (GO:0045577) IDA
  • positive regulation of B cell activation (GO:0050871) IDA
  • microglial cell activation (GO:0001774) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • positive regulation of toll-like receptor 9 signaling pathway (GO:0034165) IEA
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [638] …
transforming growth factor beta receptor 1
(Type I receptor serine/threonine kinases)
  • regulation of protein ubiquitination (GO:0031396) IDA
The role of TGFBR1 in immuno-oncology is reviewed in [4] …
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • regulation of T cell proliferation (GO:0042129) ISS
TNFR2 is a receptor for lymphotoxin-α, and the membrane form of tumour necrosis factor (TNF). It plays a variety of important roles in immune system development and regulation [229,449] …
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • natural killer cell differentiation (GO:0001779) IEA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
TYRO3 is a negative regulator of type 2 immunity [109] …
Transporters
GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • T cell proliferation involved in immune response (GO:0002309) ISS
  • macrophage activation (GO:0042116) ISS
NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [77,586,590] …
Peptide transporter 4
(SLC15 family of peptide transporters)
  • positive regulation of toll-like receptor 7 signaling pathway (GO:0034157) IMP
  • positive regulation of toll-like receptor 8 signaling pathway (GO:0034161) IMP
  • positive regulation of toll-like receptor 9 signaling pathway (GO:0034165) IMP
  • regulation of isotype switching to IgG isotypes (GO:0048302) ISS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) ISS
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430) ISS
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434) ISS
SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [351] …
Other Protein Targets
GtoPdb receptor name (family) GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulin like domain containing proteins)
  • microglial cell activation (GO:0001774) IGI
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • regulation of CD4-positive, alpha-beta T cell activation (GO:2000514) IDA
RAGE is a single chain, membrane bound immunoglobulin type protein [445,555,703] …
Aryl hydrocarbon receptor
(Aryl hydrocarbon receptor)
  • regulation of B cell proliferation (GO:0030888) IDA
The AhR is activated by small signalling molecules derived from the diet, microorganisms and environmental agents, and when expressed by immune cells, it integrates the effects of the environment and metabolism on the immune response [540] …
B7-H3 (CD276)
(Other immune checkpoint proteins, CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • T cell activation (GO:0042110) IDA
  • T cell receptor signaling pathway (GO:0050852) IBA
B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [115,168] …
baculoviral IAP repeat containing 2
(Inhibitors of apoptosis (IAP) protein family)
  • protein polyubiquitination (GO:0000209) IDA
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) IBA
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • ubiquitin protein ligase activity (GO:0061630) IBA
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
  • positive regulation of protein K63-linked ubiquitination (GO:1902523) IDA
  • positive regulation of protein K48-linked ubiquitination (GO:1902524) IDA
  • positive regulation of protein monoubiquitination (GO:1902527) IDA
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [343] …
baculoviral IAP repeat containing 3
(Inhibitors of apoptosis (IAP) protein family)
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • ubiquitin protein ligase activity (GO:0061630) IBA
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[537] …
BCL2 apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • protein polyubiquitination (GO:0000209) IDA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell proliferation (GO:0042100) IDA
  • B cell receptor signaling pathway (GO:0050853) IMP
  • B cell lineage commitment (GO:0002326) IEA
  • T cell differentiation in thymus (GO:0033077) IEA
  • CD8-positive, alpha-beta T cell lineage commitment (GO:0043375) IEA
The role of Bcl-2 family members in immunity and disease is reviewed in [170] …
BCL6 transcription repressor
(BTB (POZ) domain containing TFs)
  • positive regulation of regulatory T cell differentiation (GO:0045591) IMP
  • plasma cell differentiation (GO:0002317) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • B cell proliferation (GO:0042100) IEA
  • regulation of T cell proliferation (GO:0042129) IEA
  • regulation of memory T cell differentiation (GO:0043380) IEA
  • T-helper 2 cell differentiation (GO:0045064) IEA
  • negative regulation of T-helper 2 cell differentiation (GO:0045629) IEA
  • isotype switching to IgE isotypes (GO:0048289) IEA
  • negative regulation of isotype switching to IgE isotypes (GO:0048294) IEA
  • negative regulation of plasma cell differentiation (GO:1900099) IEA
BCL6/corepressor complexes are important for the formation of germinal centers and differentiation and proliferation of lymphocytes. Oncogenic mutations in BCL6 lead to the development of diffuse large B-cell lymphoma cells from germinal center B cells. Disruption of BCL6/corepressor complex formation by pharmacological inhibitors has therefore been identified as a novel drug mechanism with potential for the treatment of autoimmune diseases and cancer [95,104] …
butyrophilin like 3
(Butyrophilin and butyrophilin-like proteins)
  • T cell receptor signaling pathway (GO:0050852) IBA
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [164] …
butyrophilin like 8
(Butyrophilin and butyrophilin-like proteins)
  • T cell receptor signaling pathway (GO:0050852) IBA
BTNL3 and BTNL8 are two proteins expressed on the surface of human gut epithelial cells that are involved in shaping the constitution of gut resident dendritic γδ T cells [164] …
butyrophilin subfamily 3 member A1
(Butyrophilin and butyrophilin-like proteins)
  • activated T cell proliferation (GO:0050798) IMP
  • T cell receptor signaling pathway (GO:0050852) IDA
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [427] …
CD19
(CD molecules)
  • B cell proliferation involved in immune response (GO:0002322) IDA
  • antigen receptor-mediated signaling pathway (GO:0050851) IDA
  • B cell receptor signaling pathway (GO:0050853) ISS
  • regulation of B cell receptor signaling pathway (GO:0050855) IMP
  • regulation of B cell activation (GO:0050864) IDA
  • B-1 B cell differentiation (GO:0001923) IEA
CD19 is a B cell antigen used as a biomarker for normal and neoplastic B cells, and follicular dendritic cells. Anti-CD19 monoclonal antibodies are being investigated for potential clinical utility in oncology, transplantation and autimmune diseases (e.g. inebilizumab …
CD1d molecule
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • T cell selection (GO:0045058) TAS
CD1d is a lipid-binding MHC class I-like protein that is expressed by dendritic cells. CD1d presents self and microbial lipid/glycolipid antigens to unconventional T cells known as invariant natural killer T (iNKT) cells [120,689] …
CD2
(CD molecules)
  • natural killer cell activation (GO:0030101) IDA
  • positive regulation of myeloid dendritic cell activation (GO:0030887) NAS
  • T cell activation (GO:0042110) IBA
  • regulation of T cell differentiation (GO:0045580) NAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [705] …
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of T cell proliferation (GO:0042129) IDA
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response.
CD20 (membrane-spanning 4-domains, subfamily A, member 1)
(CD molecules)
  • B cell differentiation (GO:0030183) IDA
  • B cell proliferation (GO:0042100) NAS
  • B cell activation (GO:0042113) IDA
  • B cell receptor signaling pathway (GO:0050853) IDA
CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [136] …
CD22
(Other immune checkpoint proteins, CD molecules, Sialic acid binding Ig like lectins)
  • regulation of B cell proliferation (GO:0030888) ISS
  • B cell activation (GO:0042113) IDA
  • negative regulation of B cell receptor signaling pathway (GO:0050859) IDA
CD22 (SIGLEC2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation, mediates B cell-B cell interactions and may be involved in the localisation of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via
CD28
(Other immune checkpoint proteins, CD molecules)
  • T cell costimulation (GO:0031295) IBA
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • T cell activation (GO:0042110) IGI
  • regulatory T cell differentiation (GO:0045066) IDA
  • T cell receptor signaling pathway (GO:0050852) IBA
  • CD4-positive, alpha-beta T cell proliferation (GO:0035739) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • regulation of regulatory T cell differentiation (GO:0045589) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563) IEA
CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [11] …
CD300a
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • negative regulation of mast cell activation involved in immune response (GO:0033007) IDA
  • negative regulation of MyD88-dependent toll-like receptor signaling pathway (GO:0034125) IMP
  • negative regulation of mast cell degranulation (GO:0043305) IDA
  • regulation of T cell receptor signaling pathway (GO:0050856) IDA
  • negative regulation of B cell receptor signaling pathway (GO:0050859) IDA
  • negative regulation of NK T cell activation (GO:0051134) IDA
  • negative regulation of neutrophil activation (GO:1902564) IDA
  • negative regulation of eosinophil activation (GO:1902567) IDA
CD300a is a member of the CD300 family of leucocyte surface receptors [70] …
CD33
(Other immune checkpoint proteins, Sialic acid binding Ig like lectins, CD molecules)
  • immune response-inhibiting signal transduction (GO:0002765) IDA
  • negative regulation of monocyte activation (GO:0150102) IDA
CD33 (SIGLEC3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [212] …
CD38
(CD molecules, Abscisic acid receptor complex)
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell receptor signaling pathway (GO:0050853) IMP
  • B cell proliferation (GO:0042100) IEA
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [232] …
CD3e
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • T cell activation (GO:0042110) NAS
  • positive thymic T cell selection (GO:0045059) IBA
  • gamma-delta T cell activation (GO:0046629) IC
  • alpha-beta T cell activation (GO:0046631) IC
  • T cell receptor signaling pathway (GO:0050852) IC
  • T cell costimulation (GO:0031295) IEA
  • CD4-positive, alpha-beta T cell proliferation (GO:0035739) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563) IEA
CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain).

CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [153,591] …

CD4
(CD molecules)
  • T cell differentiation (GO:0030217) IDA
  • T cell activation (GO:0042110) IBA
  • T cell selection (GO:0045058) IDA
  • regulation of T cell activation (GO:0050863) IDA
  • positive regulation of T cell activation (GO:0050870) IEA
CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [330,654] …
CD47
(CD molecules)
  • positive regulation of T cell activation (GO:0050870) IDA
  • negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis (GO:1905450) ISS
CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a ‘marker of self’, and which is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal. CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [374] …
CD6
(CD molecules)
  • immunological synapse formation (GO:0001771) IMP
  • positive regulation of T cell proliferation (GO:0042102) IMP
CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes and associated with autoimmune responses. CD6 interacts with activated leucocyte-cell adhesion molecule (ALCAM/CD166), found on antigen presenting cells. This interaction induces the production of proinflammatory cytokines [435] …
CD74
(CD molecules)
  • T cell activation involved in immune response (GO:0002286) IBA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • regulation of macrophage activation (GO:0043030) NAS
  • T cell selection (GO:0045058) NAS
  • positive thymic T cell selection (GO:0045059) IEA
  • negative thymic T cell selection (GO:0045060) IEA
  • negative regulation of T cell differentiation (GO:0045581) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [137] …
CD79B
(CD molecules)
  • B cell differentiation (GO:0030183) IBA
  • B cell receptor signaling pathway (GO:0050853) IBA
CD79B is a component of the multimeric B cell antigen receptor (along with CD79A and a membrane-bound antibody that acts as the antigen recognition moiety). The CD79A/B component is responsible for signal transduction. The B cell antigen receptor complex is reported to be involved in the pathogenesis of various B cell-derived lymphoid cancers [430,562] …
CD80
(Other immune checkpoint proteins, CD molecules)
  • T cell costimulation (GO:0031295) IBA
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • negative regulation of T cell proliferation (GO:0042130) IBA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t …
CD86
(Other immune checkpoint proteins, CD molecules)
  • T cell costimulation (GO:0031295) IBA
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • B cell activation (GO:0042113) ISS
  • negative regulation of T cell proliferation (GO:0042130) IBA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) NAS
CD86 (B7-2) is a type I membrane immunoglobulin. It is expressed on antigen-presenting cells and in association with CD80 provides the costimulatory signal necessary for T cell activation and survival. CD86 interacts with CD28 or CTLA-4 on T cells. It is the interaction with CTLA-4 that is targeted …
chitinase 3 like 1
(Chitinase-like proteins)
CHI3L1 is recognised as a proinflammatory mediator in the development and progression of Th2 inflammation, such as in allergic reactions [90] …
CREB binding protein
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 …
CS1 (CD319)
(CD molecules)
  • natural killer cell activation (GO:0030101) NAS
  • T cell activation (GO:0042110) IBA
CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions.

CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomiblenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [320] …

C-type lectin domain family 12 member A
(C-type lectin-like receptors (CLRs))
The CLEC12A protein is a negative regulator of granulocyte and monocyte function [237,401] …
C-type lectin domain family 4 member A
(C-type lectin-like receptors (CLRs))
  • CD8-positive, alpha-beta T cell activation (GO:0036037) IDA
CLEC4A is an pattern recognition receptor and immunoreceptor that functions in cell adhesion, cell-cell signalling, glycoprotein turnover, and plays roles in inflammation and the immune response. It contains a immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain.
C-type lectin domain family 4 member E
(C-type lectin-like receptors (CLRs))
  • pattern recognition receptor signaling pathway (GO:0002221) IMP
  • T cell differentiation involved in immune response (GO:0002292) IEA
  • Fc-gamma receptor signaling pathway (GO:0038094) IEA
Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [81] …
C-type lectin domain family 6 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) ISS
Dectin-2 is involved in initiating the innate immune response upon recognition of high mannose structures on fungal cell walls. It associates with the ITAM-containing FcRβ adaptor and signals through the Syk, PKCδ, and CARD9-Bcl10-MALT1 pathways to promote cytokine production in response …
C-type lectin domain family 7 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) ISS
  • T cell activation (GO:0042110) TAS
  • positive regulation of lymphocyte activation (GO:0051251) IDA
Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [80] …
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(Other immune checkpoint proteins, CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
  • T cell receptor signaling pathway (GO:0050852) IBA
  • B cell receptor signaling pathway (GO:0050853) IMP
  • negative regulation of T cell proliferation (GO:0042130) IEA
CTLA-4 is expressed almost exclusively on CD4+ and CD8+ T cells. It functions as an immune checkpoint providing an inhibitory signal as a balance to stimulatory signals of the immune response i.e. it plays a crucial role in the maintenance of T cell homeostasis [413] …
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • B cell differentiation (GO:0030183) IEA
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 …
Fc fragment of IgA receptor
(CD molecules, Immunoglobulin like domain containing proteins)
  • IgA receptor activity (GO:0019766) IDA
  • Fc receptor signaling pathway (GO:0038093) IDA
  • neutrophil activation (GO:0042119) IDA
FcαRI is the cognate receptor for immunoglobulin A (IgA). In humans, IgA is predominantly expressed in the intestine, where it is important for maintaining mucosal homeostasis. IgA serves as a first-line defence to protect the gut epithelium from pathogens and enteric toxins [399,481] …
Fc fragment of IgG receptor and transporter
(Immunoglobulin C1-set domain-containing proteins)
FcRn is important for developing immunity in the fetus and neonate (transporting IgG from mother to fetus and neonate for passive immunity) [297] …
Fc fragment of IgG receptor IIIa
(CD molecules, Immunoglobulin like domain containing proteins)
  • low-affinity IgG receptor activity (GO:0019772) IDA
  • natural killer cell activation (GO:0030101) IDA
  • positive regulation of natural killer cell proliferation (GO:0032819) IDA
  • Fc-gamma receptor signaling pathway (GO:0038094) IDA
  • macrophage activation (GO:0042116) IDA
  • natural killer cell degranulation (GO:0043320) IDA
The FCGR3A gene is expressed by natural killer (NK) cells. The protein product (CD16A or FcγRIIIa) is an integral peptide-tethered membrane glycoprotein. FcγRIIIa is a low-affinity receptor for IgG Fc and is involved in removing antigen-antibody complexes from the circulation and antibody-dependent responses.

FcγRIIIa is being exploited for drug development, specifically as a NK cell-engager to mediate NK effector cell killing of cancer cells. For example, Affimed have developed , a tetravalent bispecific Fv peptide construct that simultaneously engages FcγRIIIa and CD30 on CD30-expressing malignant cells such as Hodgkin lymphoma cells, and AFM24 another tetravalent bispecific construct that targets epidermal growth factor receptor (EGFR) and FcγRIIIa to engage NK cells to destroy otherwise hard to treat EGFR-driven cancers.

COVID-19: Analysis of blood from controls and COVID-19 patients was used to show that FcγRIIIa mediates phagocytosis of antibody-opsonised SARS-CoV-2 particles by human monocytes (and macrophages) [300] …

forkhead box N1
(Forkhead box TFs)
  • T cell lineage commitment (GO:0002360) IEA
  • regulation of positive thymic T cell selection (GO:1902232) IEA
FOXN1 deficiency has been identified as the cause of the nude severe combined immunodeficiency (SCID) phenotype in mice and humans [203,499] …
heat shock protein 90 alpha family class B member 1
(Heat shock proteins)
  • regulation of protein ubiquitination (GO:0031396) IDA
HSP90AB1 chaperones both JAK2 and PRKCE, and by ensuring proper folding of these kinase proteins it is involved in the phosphorylation/activation of STAT1 [124] …
heat shock protein 90 beta family member 1
(Heat shock proteins)
HSP90B1 is an endoplasmic reticulum chaperone required for proper folding and cell surface export of newly synthesized Toll-like receptor and integrin (CD11a, CD18 and CD49d) proteins. In its absence TLR responses are ablated, and there is no innate response to microbial stimuli [520] …
ICOS (CD278)
(Other immune checkpoint proteins, CD molecules)
  • T cell costimulation (GO:0031295) IBA
Inducible T cell costimulator (ICOS) and it’s ligand constitute an immune checkpoint. ICOS is a surface receptor on activated T cells that binds its ligand on antigen presenting cells. Ligand-receptor interaction is a T cell activation signal. ICOS is a major regulator of the adaptive immune reponse that is structurally and functionally related to CD28 [269] …
immunoglobulin heavy constant epsilon
(Immunoglobulins)
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of B cell activation (GO:0050871) IBA
IgE is being investigated as a molecular target in allergic inflammatory conditions such as asthma, allergic rhinitis and chronic spontaneous urticaria. One anti-IgE monoclonal, omalizumab, has already been approved for use in patients with asthma or chronic spontaneous urticaria. Omalizumab binds t …
kelch like ECH-associated protein 1
(Kelch-like proteins)
  • protein ubiquitination (GO:0016567) IDA
Transcription of many important detoxification enzymes is regulated by the Nrf2 transcription factor, which is (negatively) regulated by interaction with KEAP1, and when activated by disengagement from KEAP1, enters the nucleus and binds genes with an antioxidant responsive element (ARE) in their promoter sequences. Nrf2-responsive genes play important roles in the cellular defense system, in the regulation of the response to oxidative stress, and facilitate detoxification, antioxidant, cytoprotective and anti-inflammatory functions. Small molecule drug-like compounds that inhibit the KEAP1-Nrf2 protein-protein interaction (a.k.a. Nrf2 activators) are being developed for their potential anti-inflammatory action. The approved MS prodrug was reported to exploit this molecular mechanism, although more recent evidence suggests that its effects may be Nrf2 independent [560] …
LAG3 (CD223)
(Other immune checkpoint proteins, CD molecules)
  • plasmacytoid dendritic cell activation (GO:0002270) ISS
  • negative regulation of regulatory T cell differentiation (GO:0045590) ISS
  • T cell activation (GO:0042110) IEA
Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [18,224] …
leucine rich repeat containing 32
(Leucine-rich repeat proteins)
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
GARP is expressed on the surface of T regulatory (Treg) cells and binds latent (inactive) TGF-β1. GARP is also involved in the activation of TGF-β1 [141] …
leukocyte associated immunoglobulin like receptor 1 (CD305)
(CD molecules)
LAIR1 has been identified as a potential molecular receptor for Plasmodium falciparum-coded proteins that are expressed by infected host erythrocytes. Interaction of these parasite RIFIN proteins (encoded by rif genes) and inhibitory leucocyte receptors such as LAIR1 may mediate parasite-driven evasion of the host’s immune system [546] …
leukocyte immunoglobulin like receptor A4 (CD85g)
(CD molecules)
  • negative regulation of toll-like receptor 7 signaling pathway (GO:0034156) IMP
  • negative regulation of toll-like receptor 9 signaling pathway (GO:0034164) IMP
  • Fc-epsilon receptor signaling pathway (GO:0038095) IMP
LILRA4 (CD85g) is a member of the activating leukocyte immunoglobulin like receptor (LILRA) family (HGNC family 1181). It is involved in activation of eosinophils and homeostatic regulation of the innate immunity of plasmacytoid dendritic cells (pDCs) [93] …
leukocyte immunoglobulin like receptor B1 (CD85j)
(CD molecules, Other immune checkpoint proteins)
  • T cell proliferation involved in immune response (GO:0002309) IDA
  • immune response-inhibiting cell surface receptor signaling pathway (GO:0002767) NAS
  • Fc receptor mediated inhibitory signaling pathway (GO:0002774) IDA
  • negative regulation of T cell proliferation (GO:0042130) IDA
  • negative regulation of alpha-beta T cell activation (GO:0046636) IDA
  • negative regulation of CD8-positive, alpha-beta T cell activation (GO:2001186) IDA
  • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
  • positive regulation of gamma-delta T cell activation involved in immune response (GO:2001193) IDA
LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9P06702; which also binds TLR4 and RAGE) [84] …
lymphocyte antigen 96
(Lymphocyte antigens)
  • lipopolysaccharide immune receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) IDA
  • toll-like receptor 4 signaling pathway (GO:0034142) ISS
LY96 (MD2) is a binding partner of Toll-like receptor 4 (TLR4), required to initiate an innate immune response to bacterial lipopolysaccharide (LPS). The signaling complex also contains CD14 co-receptor [324] …
MALT1 paracaspase
(Immunoglobulin like domain containing proteins)
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) NAS
  • B cell activation (GO:0042113) IBA
  • T cell receptor signaling pathway (GO:0050852) IDA
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) ISS
  • B-1 B cell differentiation (GO:0001923) IEA
  • T cell proliferation (GO:0042098) IEA
  • regulation of T cell receptor signaling pathway (GO:0050856) IEA
MALT1 inhibition is considered a tractable mechanism for the treatment of severe autoimmune diseases. The MALT1 inhibitory action of (a.k.a. mepazine) is reported to be effecacious in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis [411] …
myeloid cell nuclear differentiation antigen
(Absent in melanoma (AIM)-like receptors (ALRs))
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • B cell receptor signaling pathway (GO:0050853) IMP
MNDA can be detected exclusively in nuclei of hematopoietic cells of the monocyte lineage. Expression is induced by interferon α [76] …
NFKB inhibitor zeta
(NF-κB regulators)
  • T cell receptor signaling pathway (GO:0050852) ISS
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) ISS
IκBζ is a key component of the immune response that regulates the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. IκBζ acts as an inhibitor of primary NF-κB response genes, but may also act as a coactivator of the expression of secondary response genes (through association with the NF-κB p50 subunit). IκBζ is in fact the product of a primary NF-κB reponse gene, being rapidly upregulated by various inflammatory stimuli. Pro-inflammatory gene products that are regulated by IκBζ include CCL2, IL-6, IL12p40, IL-17, IFNγ, and GM-CSF [294,312] …
nuclear factor, erythroid 2 like 2
(Basic leucine zipper domain TFs)
  • protein ubiquitination (GO:0016567) IDA
NRF2 is included in GToImmuPdb as mutations in this gene have been reported in patients with IMDDHH, an inherited disease in which some of the symptoms arise from defective immune system function [268] …
perforin 1
(Cytolytic pore-forming proteins)
  • immunological synapse formation (GO:0001771) IDA
Perforin 1 is expressed only in the secretory granules of cytotoxic T cells and natural killer (NK) cells, and it is an essential component of the immune system. These cell types release perforin 1 close to target cells (e.g. virus-infected and neoplastic cells) in process is known as the granule exocytosis pathway [154] …
programmed cell death 1 (CD279)
(Other immune checkpoint proteins, CD molecules)
Immune checkpoint blockade in oncology:
Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called ‘immune checkpoints’, which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [482] …
PVR related immunoglobulin domain containing
(Other immune checkpoint proteins)
  • negative regulation of T cell receptor signaling pathway (GO:0050860) IMP
PVRIG has been identified as a novel co-inhibitory immune checkpoint, that is exploited by some cancer cells to evade immune detection [433,683] …
RAS guanyl releasing protein 1
(EF-hand domain containing proteins)
  • natural killer cell activation (GO:0030101) IMP
  • T cell proliferation (GO:0042098) IMP
  • B cell proliferation (GO:0042100) IMP
  • T cell activation (GO:0042110) IMP
  • B cell activation (GO:0042113) IMP
  • positive regulation of natural killer cell differentiation (GO:0032825) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • mast cell degranulation (GO:0043303) IEA
RAS guanyl releasing protein 1 (RASGRP1) functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor. It activates Ras and the downstream Erk/MAP kinase cascade. RASGRP1 regulates the development, homeostasis and differentiation of T aand B cells [225,512,570] …
S100 calcium binding protein A11
(EF-hand domain containing proteins)
S100A11 is a pro-inflammatory calcium-binding protein. Elevated S100A11 has been reported as a marker of disease activity and extramuscular manifestations in inflammatory myopathies [19] …
signal transducer and activator of transcription 3
(STAT transcription factors)
  • T-helper 17 cell lineage commitment (GO:0072540) ISS
STAT3 regulates the expression of a variety of genes in response to cytokines and growth factors (e.g. IFNs, EGF, IL-5, IL-6, HGF, LIF and BMP2) and plays important roles in several cellular processes, including cell growth and apoptosis. STAT3 is a crucial component of the JAK/STAT signalling pathway that is implicated in cancer and inflammation. STAT3 is frequently activated in cancers, where it downmodulates intrinsic immune surveillance of tumour cells. Phosphorylated (activated) STAT3 (pSTAT3) is a marker of poor cancer prognosis [716,723] …
signal transducer and activator of transcription 6
(STAT transcription factors)
  • T-helper 1 cell lineage commitment (GO:0002296) IEA
  • isotype switching to IgE isotypes (GO:0048289) IEA
  • positive regulation of isotype switching to IgE isotypes (GO:0048295) IEA
STAT6 plays a central role in exerting IL-4 mediated biological responses. The prosurvival activity of the Th2 cytokine IL-4 is mediated by STAT6-dependent transcription of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL). This mechanism explains the resistance to apoptosis that is observed epithelial tumours which produce IL-4 [627] …
SIRPA (CD172a)
(CD molecules, Signal regulatory proteins)
  • positive regulation of T cell activation (GO:0050870) IBA
SIRPα is an important inhibitory immune response regulator. In interaction with CD47, SIRPα controls an inhibitory innate immune checkpoint that provides an anti-phagocytic (do not eat) signal. SIRPα is predominantly expressed by macrophages. Laboratory work has established that SIRPα is expressed by a subset of intestinal dendritic cells (integrin CD103+ DCs) that are critical for maintaining intestinal (mucosal) immune system homeostasis. This subset of CD103+SIRPα+ DCs selectively activates Th17 cells and type 3 innate lymphoid cells (ILC3) [292,673] …
stimulator of interferon response cGAMP interactor 1
(Other pattern recognition receptors)
STING functions as a major regulator of the innate immune response to viral and bacterial infections [379] …
TIGIT
(Other immune checkpoint proteins, Immunoglobulin like domain containing proteins)
  • negative regulation of T cell activation (GO:0050868) IDA
TIGIT is now considered as an alternate inhibitory immune checkpoint protein which may have potential immunotherapeutic potential, particularly in conditions refractory to more established PD-1 checkpoint inhibition. Given its presence on T cells and NK cells, TIGIT offers an intervention point for targeting both the adaptive and innate arms of the immune system. Clinical development of anti-TIGIT monoclonal antibodies is in preliminary stages. Combination therapies with existing immune checkpoint inhibitors are considered particularly promising. MTIG7192A (NCT02794571 …
TIM3 (CD366)
(Other immune checkpoint proteins, CD molecules)
  • negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
  • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
  • macrophage activation involved in immune response (GO:0002281) IEA
  • negative regulation of natural killer cell activation (GO:0032815) IEA
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • toll-like receptor 7 signaling pathway (GO:0034154) IEA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • negative regulation of immunological synapse formation (GO:2000521) IEA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [426] …
V-set immunoregulatory receptor
(Other immune checkpoint proteins)
  • positive regulation of regulatory T cell differentiation (GO:0045591) IMP
  • negative regulation of alpha-beta T cell activation (GO:0046636) IBA
  • negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562) IMP
  • negative regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000565) IMP
V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [365] …
X-linked inhibitor of apoptosis
(Inhibitors of apoptosis (IAP) protein family)
  • ubiquitin-protein transferase activity (GO:0004842) IDA
  • positive regulation of protein ubiquitination (GO:0031398) IDA
  • ubiquitin protein ligase activity (GO:0061630) EXP
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
  • positive regulation of protein linear polyubiquitination (GO:1902530) IDA
Mouse experiments suggest that XIAP regulates innate immune responses (to Listeria monocytogenes infection) by potentiating synergy between Toll-like receptors (TLRs) and NOD-like receptors (NLRs) through activation of JNK- and NF-κB-dependent signaling [47] …

Tyrosine-protein kinase SYK

TARGET ACTIONS ORGANISM
ATyrosine-protein kinase SYK
inhibitor
Humans
UAdenosine receptor A3
antagonist
Humans
Uvesicular monoamine transporter 2 (VMAT2)
inhibitor
Humans
UFatty-acid amide hydrolase 1
inhibitor
Humans
UEquilibrative nucleoside transporter 1
inhibitor
Humans
UUDP-glucuronosyltransferase 1-1
inhibitor
Humans
UcGMP-specific 3′,5′-cyclic phosphodiesterase
inhibitor
Humans
UArachidonate 5-lipoxygenase
inhibitor
Humans
UCathepsin S
inhibitor
Humans
UCathepsin L1
inhibitor
Humans
UTyrosine-protein kinase ABL1
inhibitor
Humans
UCalcium-dependent protein kinase 1
inhibitor
Plasmodium falciparum (isolate 3D7)
USerine/threonine-protein kinase PknB
inhibitor
Mycobacterium tuberculosis
URibosomal protein S6 kinase alpha-6
inhibitor
Humans
UNon-receptor tyrosine-protein kinase TYK2
inhibitor
Humans
UAtypical kinase COQ8A, mitochondrial
inhibitor
Humans
UTyrosine-protein kinase JAK1
inhibitor
Humans
UHepatocyte growth factor receptor
inhibitor
Humans
USerine/threonine-protein kinase NIM1
inhibitor
Humans
USerine/threonine-protein kinase MST4
inhibitor
Humans
UcAMP-dependent protein kinase catalytic subunit alpha
inhibitor
Humans
USerine/threonine-protein kinase 24
inhibitor
Humans
USerine/threonine-protein kinase 3
inhibitor
Humans
UTyrosine-protein kinase Tec
inhibitor
Humans
USerine/threonine-protein kinase 33
inhibitor
Humans
USerine/threonine-protein kinase 35
inhibitor
Humans
USerine/threonine-protein kinase 36
inhibitor
Humans
USerine/threonine-protein kinase 38
inhibitor
Humans
USerine/threonine-protein kinase 38-like
inhibitor
Humans
USTE20/SPS1-related proline-alanine-rich protein kinase
inhibitor
Humans
USerine/threonine-protein kinase TAO1
inhibitor
Humans
USerine/threonine-protein kinase TAO2
inhibitor
Humans
USerine/threonine-protein kinase TAO3
inhibitor
Humans
USerine/threonine-protein kinase TBK1
inhibitor
Humans
UAngiopoietin-1 receptor
inhibitor
Humans
UDual specificity testis-specific protein kinase 1
inhibitor
Humans
UTGF-beta receptor type-1
inhibitor
Humans
UTGF-beta receptor type-2
inhibitor
Humans
UTyrosine-protein kinase receptor Tie-1
inhibitor
Humans
USerine/threonine-protein kinase tousled-like 1
inhibitor
Humans
USerine/threonine-protein kinase tousled-like 2
inhibitor
Humans
UTRAF2 and NCK-interacting protein kinase
inhibitor
Humans
UNon-receptor tyrosine-protein kinase TNK1
inhibitor
Humans
UActivated CDC42 kinase 1
inhibitor
Humans
USerine/threonine-protein kinase TNNI3K
inhibitor
Humans
UTestis-specific serine/threonine-protein kinase 1
inhibitor
Humans
UDual specificity protein kinase TTK
inhibitor
Humans
UTyrosine-protein kinase TXK
inhibitor
Humans
UTyrosine-protein kinase receptor TYRO3
inhibitor
Humans
USerine/threonine-protein kinase ULK1
inhibitor
Humans
USerine/threonine-protein kinase ULK2
inhibitor
Humans
USerine/threonine-protein kinase ULK3
inhibitor
Humans
UWee1-like protein kinase
inhibitor
Humans
UTyrosine-protein kinase Yes
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 19
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase MLT
inhibitor
Humans
UTyrosine-protein kinase ZAP-70
inhibitor
Humans
UAP2-associated protein kinase 1
inhibitor
Humans
UAbelson tyrosine-protein kinase 2
inhibitor
Humans
UActivin receptor type-1
inhibitor
Humans
UActivin receptor type-1B
inhibitor
Humans
UAtypical kinase COQ8B, mitochondrial
inhibitor
Humans
UALK tyrosine kinase receptor
inhibitor
Humans
UAnkyrin repeat and protein kinase domain-containing protein 1
inhibitor
Humans
UAurora kinase A
inhibitor
Humans
UAurora kinase B
inhibitor
Humans
UAurora kinase C
inhibitor
Humans
UTyrosine-protein kinase receptor UFO
inhibitor
Humans
UTyrosine-protein kinase Blk
inhibitor
Humans
UBMP-2-inducible protein kinase
inhibitor
Humans
UBone morphogenetic protein receptor type-1B
inhibitor
Humans
UBone morphogenetic protein receptor type-2
inhibitor
Humans
UCytoplasmic tyrosine-protein kinase BMX
inhibitor
Humans
USerine/threonine-protein kinase B-raf
inhibitor
Humans
UTyrosine-protein kinase BTK
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type 1
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type 1D
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type 1G
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type II subunit alpha
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type II subunit beta
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type II subunit delta
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase type II subunit gamma
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase kinase 1
inhibitor
Humans
UCalcium/calmodulin-dependent protein kinase kinase 2
inhibitor
Humans
UPeripheral plasma membrane protein CASK
inhibitor
Humans
UKappa-casein
inhibitor
Humans
UCyclin-dependent kinase 1
inhibitor
Humans
USerine/threonine-protein kinase MRCK gamma
inhibitor
Humans
UCyclin-dependent kinase 4
inhibitor
Humans
UCyclin-dependent kinase-like 1
inhibitor
Humans
UCyclin-dependent kinase-like 2
inhibitor
Humans
USerine/threonine-protein kinase Chk1
inhibitor
Humans
USerine/threonine-protein kinase Chk2
inhibitor
Humans
UCitron Rho-interacting kinase
inhibitor
Humans
UDual specificity protein kinase CLK1
inhibitor
Humans
UDual specificity protein kinase CLK2
inhibitor
Humans
UDual specificity protein kinase CLK3
inhibitor
Humans
UDual specificity protein kinase CLK4
inhibitor
Humans
UMacrophage colony-stimulating factor 1 receptor
inhibitor
Humans
UTyrosine-protein kinase CSK
inhibitor
Humans
UCasein kinase I isoform alpha
inhibitor
Humans
UCasein kinase II subunit alpha
inhibitor
Humans
UCasein kinase II subunit alpha’
inhibitor
Humans
UDeath-associated protein kinase 1
inhibitor
Humans
UDeath-associated protein kinase 2
inhibitor
Humans
UDeath-associated protein kinase 3
inhibitor
Humans
USerine/threonine-protein kinase DCLK1
inhibitor
Humans
USerine/threonine-protein kinase DCLK2
inhibitor
Humans
USerine/threonine-protein kinase DCLK3
inhibitor
Humans
UEpithelial discoidin domain-containing receptor 1
inhibitor
Humans
UDiscoidin domain-containing receptor 2
inhibitor
Humans
UDual specificity tyrosine-phosphorylation-regulated kinase 1A
inhibitor
Humans
UDual specificity tyrosine-phosphorylation-regulated kinase 1B
inhibitor
Humans
UEpidermal growth factor receptor
inhibitor
Humans
UEukaryotic translation initiation factor 2-alpha kinase 1
inhibitor
Humans
UInterferon-induced, double-stranded RNA-activated protein kinase
inhibitor
Humans
UeIF-2-alpha kinase GCN2
inhibitor
Humans
UEphrin type-A receptor 1
inhibitor
Humans
UEphrin type-A receptor 2
inhibitor
Humans
UEphrin type-A receptor 3
inhibitor
Humans
UEphrin type-A receptor 4
inhibitor
Humans
UEphrin type-A receptor 5
inhibitor
Humans
UEphrin type-A receptor 6
inhibitor
Humans
UEphrin type-A receptor 7
inhibitor
Humans
UEphrin type-A receptor 8
inhibitor
Humans
UEphrin type-B receptor 1
inhibitor
Humans
UEphrin type-B receptor 2
inhibitor
Humans
UEphrin type-B receptor 4
inhibitor
Humans
UEphrin type-B receptor 6
inhibitor
Humans
UReceptor tyrosine-protein kinase erbB-2
inhibitor
Humans
UReceptor tyrosine-protein kinase erbB-4
inhibitor
Humans
USerine/threonine-protein kinase/endoribonuclease IRE1
inhibitor
Humans
UTyrosine-protein kinase Fer
inhibitor
Humans
UTyrosine-protein kinase Fes/Fps
inhibitor
Humans
UFibroblast growth factor receptor 1
inhibitor
Humans
UFibroblast growth factor receptor 2
inhibitor
Humans
UFibroblast growth factor receptor 3
inhibitor
Humans
UTyrosine-protein kinase Fgr
inhibitor
Humans
UVascular endothelial growth factor receptor 1
inhibitor
Humans
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Humans
UVascular endothelial growth factor receptor 3
inhibitor
Humans
USerine/threonine-protein kinase mTOR
inhibitor
Humans
UTyrosine-protein kinase FRK
inhibitor
Humans
UTyrosine-protein kinase Fyn
inhibitor
Humans
UCyclin-G-associated kinase
inhibitor
Humans
UGlycogen synthase kinase-3 alpha
inhibitor
Humans
UGlycogen synthase kinase-3 beta
inhibitor
Humans
UTyrosine-protein kinase HCK
inhibitor
Humans
UHomeodomain-interacting protein kinase 2
inhibitor
Humans
UHomeodomain-interacting protein kinase 3
inhibitor
Humans
USerine/threonine-protein kinase ICK
inhibitor
Humans
UInhibitor of nuclear factor kappa-B kinase subunit beta
inhibitor
Humans
UInhibitor of nuclear factor kappa-B kinase subunit epsilon
inhibitor
Humans
UInsulin receptor
inhibitor
Humans
UInsulin receptor-related protein
inhibitor
Humans
UInterleukin-1 receptor-associated kinase 1
inhibitor
Humans
UInterleukin-1 receptor-associated kinase 3
inhibitor
Humans
UInterleukin-1 receptor-associated kinase 4
inhibitor
Humans
UTyrosine-protein kinase ITK/TSK
inhibitor
Humans
UTyrosine-protein kinase JAK2
inhibitor
Humans
UTyrosine-protein kinase JAK3
inhibitor
Humans
UVascular endothelial growth factor receptor 2
inhibitor
Humans
USerine/threonine-protein kinase SIK3
inhibitor
Humans
UMast/stem cell growth factor receptor Kit
inhibitor
Humans
USerine/threonine-protein kinase LATS1
inhibitor
Humans
UTyrosine-protein kinase Lck
inhibitor
Humans
ULIM domain kinase 1
inhibitor
Humans
ULIM domain kinase 2
inhibitor
Humans
ULeucine-rich repeat serine/threonine-protein kinase 2
inhibitor
Humans
ULeukocyte tyrosine kinase receptor
inhibitor
Humans
UTyrosine-protein kinase Lyn
inhibitor
Humans
UDual specificity mitogen-activated protein kinase kinase 2
inhibitor
Humans
UDual specificity mitogen-activated protein kinase kinase 3
inhibitor
Humans
UDual specificity mitogen-activated protein kinase kinase 5
inhibitor
Humans
UDual specificity mitogen-activated protein kinase kinase 6
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 1
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 10
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 11
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 12
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 13
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 15
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 2
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 3
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 4
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 6
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase 9
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase kinase 1
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase kinase 2
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase kinase 3
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase kinase 4
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase kinase 5
inhibitor
Humans
UMitogen-activated protein kinase 10
inhibitor
Humans
UMitogen-activated protein kinase 13
inhibitor
Humans
UMitogen-activated protein kinase 14
inhibitor
Humans
UMitogen-activated protein kinase 15
inhibitor
Humans
UMitogen-activated protein kinase 4
inhibitor
Humans
UMitogen-activated protein kinase 7
inhibitor
Humans
UMitogen-activated protein kinase 9
inhibitor
Humans
UMAP kinase-activated protein kinase 5
inhibitor
Humans
USerine/threonine-protein kinase MARK1
inhibitor
Humans
USerine/threonine-protein kinase MARK2
inhibitor
Humans
UMAP/microtubule affinity-regulating kinase 3
inhibitor
Humans
UMAP/microtubule affinity-regulating kinase 4
inhibitor
Humans
UCLIP-associating protein 1
inhibitor
Humans
UMicrotubule-associated serine/threonine-protein kinase 1
inhibitor
Humans
UMegakaryocyte-associated tyrosine-protein kinase
inhibitor
Humans
UMaternal embryonic leucine zipper kinase
inhibitor
Humans
UTyrosine-protein kinase Mer
inhibitor
Humans
UMisshapen-like kinase 1
inhibitor
Humans
UMAP kinase-interacting serine/threonine-protein kinase 1
inhibitor
Humans
UMAP kinase-interacting serine/threonine-protein kinase 2
inhibitor
Humans
UMacrophage-stimulating protein receptor
inhibitor
Humans
UMuscle, skeletal receptor tyrosine-protein kinase
inhibitor
Humans
UMyosin light chain kinase, smooth muscle
inhibitor
Humans
UMyosin light chain kinase 2, skeletal/cardiac muscle
inhibitor
Humans
UMyosin light chain kinase 3
inhibitor
Humans
UMyosin light chain kinase family member 4
inhibitor
Humans
UMyosin-IIIa
inhibitor
Humans
USerine/threonine-protein kinase Nek1
inhibitor
Humans
USerine/threonine-protein kinase Nek11
inhibitor
Humans
USerine/threonine-protein kinase Nek2
inhibitor
Humans
USerine/threonine-protein kinase Nek3
inhibitor
Humans
USerine/threonine-protein kinase Nek4
inhibitor
Humans
USerine/threonine-protein kinase Nek5
inhibitor
Humans
USerine/threonine-protein kinase Nek9
inhibitor
Humans
UHigh affinity nerve growth factor receptor
inhibitor
Humans
UBDNF/NT-3 growth factors receptor
inhibitor
Humans
UNT-3 growth factor receptor
inhibitor
Humans
UNUAK family SNF1-like kinase 1
inhibitor
Humans
UNUAK family SNF1-like kinase 2
inhibitor
Humans
USerine/threonine-protein kinase OSR1
inhibitor
Humans
USerine/threonine-protein kinase PAK 1
inhibitor
Humans
USerine/threonine-protein kinase PAK 2
inhibitor
Humans
USerine/threonine-protein kinase PAK 3
inhibitor
Humans
USerine/threonine-protein kinase PAK 4
inhibitor
Humans
USerine/threonine-protein kinase PAK 6
inhibitor
Humans
USerine/threonine-protein kinase PAK 5
inhibitor
Humans
UCyclin-dependent kinase 16
inhibitor
Humans
UCyclin-dependent kinase 17
inhibitor
Humans
UPlatelet-derived growth factor receptor alpha
inhibitor
Humans
UPlatelet-derived growth factor receptor beta
inhibitor
Humans
U3-phosphoinositide-dependent protein kinase 1
inhibitor
Humans
UCyclin-dependent kinase 15
inhibitor
Humans
UPhosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform
inhibitor
Humans
UPhosphatidylinositol 4-kinase beta
inhibitor
Humans
UPhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
inhibitor
Humans
UPhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma
inhibitor
Humans
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
inhibitor
Humans
UPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
inhibitor
Humans
USerine/threonine-protein kinase pim-1
inhibitor
Humans
USerine/threonine-protein kinase pim-3
inhibitor
Humans
UPhosphatidylinositol 5-phosphate 4-kinase type-2 beta
inhibitor
Humans
UPhosphatidylinositol 5-phosphate 4-kinase type-2 gamma
inhibitor
Humans
UMembrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
inhibitor
Humans
USerine/threonine-protein kinase N1
inhibitor
Humans
USerine/threonine-protein kinase N2
inhibitor
Humans
USerine/threonine-protein kinase PLK1
inhibitor
Humans
USerine/threonine-protein kinase PLK2
inhibitor
Humans
USerine/threonine-protein kinase PLK3
inhibitor
Humans
USerine/threonine-protein kinase PLK4
inhibitor
Humans
U5′-AMP-activated protein kinase catalytic subunit alpha-1
inhibitor
Humans
U5′-AMP-activated protein kinase
inhibitor
Humans
UcAMP-dependent protein kinase catalytic subunit beta
inhibitor
Humans
UProtein kinase C delta type
inhibitor
Humans
UProtein kinase C epsilon type
inhibitor
Humans
UProtein kinase C gamma type (PRKCG)
inhibitor
Humans
UProtein kinase C iota type
inhibitor
Humans
UProtein kinase C theta type
inhibitor
Humans
USerine/threonine-protein kinase D1
inhibitor
Humans
UcGMP-dependent protein kinase 2
inhibitor
Humans
USerine/threonine-protein kinase PRP4 homolog
inhibitor
Humans
UFocal adhesion kinase 1
inhibitor
Humans
UProtein-tyrosine kinase 2-beta
inhibitor
Humans
UProtein-tyrosine kinase 6
inhibitor
Humans
URAF proto-oncogene serine/threonine-protein kinase
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Humans
USerine/threonine-protein kinase RIO1
inhibitor
Humans
USerine/threonine-protein kinase RIO2
inhibitor
Humans
USerine/threonine-protein kinase RIO3
inhibitor
Humans
UReceptor-interacting serine/threonine-protein kinase 1
inhibitor
Humans
UReceptor-interacting serine/threonine-protein kinase 2
inhibitor
Humans
UReceptor-interacting serine/threonine-protein kinase 4
inhibitor
Humans
URho-associated protein kinase 2
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase ROS
inhibitor
Humans
URibosomal protein S6 kinase alpha-1
inhibitor
Humans
URibosomal protein S6 kinase alpha-3
inhibitor
Humans
USerine/threonine-protein kinase SBK1
inhibitor
Humans
UUncharacterized serine/threonine-protein kinase SBK3
inhibitor
Humans
USerine/threonine-protein kinase Sgk3
inhibitor
Humans
USerine/threonine-protein kinase SIK1
inhibitor
Humans
USerine/threonine-protein kinase SIK2
inhibitor
Humans
USTE20-like serine/threonine-protein kinase
inhibitor
Humans
USNF-related serine/threonine-protein kinase
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase Src
inhibitor
Humans
UTyrosine-protein kinase Srms
inhibitor
Humans
USerine/threonine-protein kinase 10
inhibitor
Humans
USerine/threonine-protein kinase 16
inhibitor
Humans
USerine/threonine-protein kinase 17A
inhibitor
Humans
USerine/threonine-protein kinase 17B
inhibitor
Humans
USerine/threonine-protein kinase 32A
inhibitor
Humans
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