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Targets Associated to Immuno Processes - Chemotaxis & migration

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Chemotaxis & migration Download as CSV
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ACKR1
(Chemokine receptors)
  • regulation of chemokine production (GO:0032642) IBA
  • chemokine-mediated signaling pathway (GO:0070098) IEA
ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Studies in ACKR1 null mice, and analysis of ACKR1 SNPs in asthmatic patients with poorly controlled symptoms, suggest a role for this cytokine receptor in the temporal regulation of asthma pathophysiology and symptoms [76] ...
ACKR2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ACKR3
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IMP
ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. ACKR3 binds the chemokine CXCL12 (stromal cell-derived factor 1, SDF-1 which is also a ligand for CXCR4). ACKR3 is an atypical receptor in that it does not activate G-protein-mediated signaling but induces β-arrestin recruitment [185] ...
ACKR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
ACKR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ADGRE2
(Adhesion Class GPCRs)
  • granulocyte chemotaxis (GO:0071621) 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 [160] ...
A1 receptor
(Adenosine receptors)
  • negative regulation of leukocyte migration (GO:0002686) IEA
  • leukocyte migration (GO:0050900) IEA
Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A1 receptor in ade ...
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 [397] ...
A2B receptor
(Adenosine receptors)
  • positive regulation of chemokine production (GO:0032722) IEA
A2B receptor is discussed in this immuno-oncology review [3] ...
B1 receptor
(Bradykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
Bradykinin ...
C3a receptor
(Complement peptide receptors)
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
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 [379,414] ...
C5a1 receptor
(Complement peptide receptors)
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • neutrophil chemotaxis (GO:0030593) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
C5aR is typically associated with the compement cascade and innate immunity.
MorphoSys have an anti-C5aR monoclonal antibody (MOR210; TJ210) 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 [159,246,282-283] ...
C5a2 receptor
(Complement peptide receptors)
  • negative regulation of neutrophil chemotaxis (GO:0090024) IMP
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.
CB2 receptor
(Cannabinoid receptors)
  • leukocyte chemotaxis (GO:0030595) 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 [292] ...
CCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IDA
  • chemokine-mediated signaling pathway (GO:0070098) IDA
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR10
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR10 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
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • chemokine receptor activity (GO:0004950) TAS
  • positive regulation of T cell chemotaxis (GO:0010820) ISS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • monocyte extravasation (GO:0035696) ISS
  • T-helper 17 cell chemotaxis (GO:0035705) ISS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) ISS
  • positive regulation of T cell activation (GO:0050870) ISS
  • chemokine-mediated signaling pathway (GO:0070098) ISS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • macrophage migration (GO:1905517) ISS
  • positive regulation of thymocyte migration (GO:2000412) ISS
  • positive regulation of monocyte extravasation (GO:2000439) ISS
  • positive regulation of CD8-positive, alpha-beta T cell extravasation (GO:2000451) 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 [3] ...
CCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [361] ...
CCR5
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
CCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR5 is discussed in relation to immuno-oncology in [3] ...
CCR6
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
  • lymphocyte migration (GO:0072676) ISS
  • T cell migration (GO:0072678) ISS
  • thymocyte migration (GO:0072679) ISS
  • regulation of T cell migration (GO:2000404) ISS
  • positive regulation of dendritic cell chemotaxis (GO:2000510) IBA
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 [200,232] ...
CCR7
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) IC
  • myeloid dendritic cell chemotaxis (GO:0002408) IDA
  • C-C chemokine receptor activity (GO:0016493) ISS
  • C-C motif chemokine 19 receptor activity (GO:0038117) IDA
  • C-C motif chemokine 21 receptor activity (GO:0038121) IDA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IDA
  • lymphocyte migration into lymph node (GO:0097022) TAS
  • positive regulation of dendritic cell chemotaxis (GO:2000510) ISS
  • positive regulation of T cell costimulation (GO:2000525) ISS
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.
CCR8
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCR8 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)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
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 [415] ...
CCRL2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
CCRL2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. However, the nomenclature of CCLR2 for this receptor and its classification as a member of the chemokine receptor family is prov ...
chemerin receptor 1
(Chemerin receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • positive regulation of macrophage chemotaxis (GO:0010759) IMP
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 [138] ...
CXCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • interleukin-8 receptor activity (GO:0004918) IDA
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • neutrophil chemotaxis (GO:0030593) IBA
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 [3] ...
CXCR2
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • interleukin-8 receptor activity (GO:0004918) IDA
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IDA
  • neutrophil chemotaxis (GO:0030593) IDA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
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 [3] ...
CXCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • regulation of leukocyte migration (GO:0002685) IEA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.

In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [63] ...
CXCR4
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) NAS
  • C-X-C motif chemokine 12 receptor activity (GO:0038147) IDA
  • CXCL12-activated CXCR4 signaling pathway (GO:0038160) IDA
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 [327,342,403,410] ...
CXCR5
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
  • leukocyte chemotaxis (GO:0030595) 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.
CXCR6
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [391] ...
CX3CR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
  • C-X3-C chemokine receptor activity (GO:0016495) IDA
  • leukocyte chemotaxis (GO:0030595) ISS
  • leukocyte tethering or rolling (GO:0050901) ISS
  • regulation of microglial cell migration (GO:1904139) TAS
  • positive regulation of monocyte chemotaxis (GO:0090026) IEA
  • positive regulation of microglial cell migration (GO:1904141) IEA
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)
  • negative regulation of eosinophil extravasation (GO:2000420) IDA
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 [436] ...
FFA2 receptor
(Free fatty acid receptors)
  • leukocyte chemotaxis involved in inflammatory response (GO:0002232) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
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 [431] ...
FFA3 receptor
(Free fatty acid receptors)
  • positive regulation of chemokine production (GO:0032722) ISS
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [49] ...
FPR2/ALX
(Formylpeptide receptors, Leukotriene receptors)
  • positive regulation of monocyte chemotaxis (GO:0090026) IGI
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 [405] ...
H1 receptor
(Histamine receptors)
  • eosinophil chemotaxis (GO:0048245) IEA
The H1 receptor was the first of the family to be targeted for clinical use, with antagonists (anti-histamines) developed that are still used widely to treat allergic inflammation such as rhinitis, allergic conjunctivitis, urticaria and even anaphylaxis.
GPR15
(Class A Orphans)
  • T cell migration (GO:0072678) IEA
Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [140,281,290,376] ...
GPR183
(Class A Orphans)
  • dendritic cell chemotaxis (GO:0002407) ISS
  • T cell chemotaxis (GO:0010818) ISS
  • leukocyte chemotaxis (GO:0030595) IMP
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 [193,310] ...
GPR35
(Class A Orphans)
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IDA
GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17 [314] ...
NK1 receptor
(Tachykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
PAF receptor
(Platelet-activating factor receptor)
  • positive regulation of cellular extravasation (GO:0002693) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
PAF deficiency results in defective inflammatory response to infection in mice.
PAR2
(Proteinase-activated receptors)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IDA
  • negative regulation of chemokine production (GO:0032682) IDA
  • positive regulation of chemokine production (GO:0032722) IDA
  • leukocyte migration (GO:0050900) IDA
  • regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000341) 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) [125] ...
S1P1 receptor
(Lysophospholipid (S1P) receptors)
  • T cell migration (GO:0072678) ISS
  • leukocyte chemotaxis (GO:0030595) IEA
S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [166,169,341] ...
XCR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IBA
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [223] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
P2X4
(P2X receptors)
  • positive regulation of microglial cell migration (GO:1904141) ISS
P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [52,70] ...
TRPM2
(Transient Receptor Potential channels (TRP))
  • dendritic cell chemotaxis (GO:0002407) ISS
Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [304] ...
TRPM4
(Transient Receptor Potential channels (TRP))
  • dendritic cell chemotaxis (GO:0002407) ISS
TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [304] ...
TRPV4
(Transient Receptor Potential channels (TRP))
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
  • positive regulation of macrophage inflammatory protein 1 alpha production (GO:0071642) IEA
  • positive regulation of chemokine (C-C motif) ligand 5 production (GO:0071651) IEA
  • positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340) IEA
Expressed on mouse neutrophils [304] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • negative regulation of monocyte chemotactic protein-1 production (GO:0071638) 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) [346] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
5-LOX
(Lipoxygenases)
  • leukocyte chemotaxis involved in inflammatory response (GO:0002232) IMP
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • dendritic cell migration (GO:0036336) ISS
  • positive regulation of leukocyte adhesion to arterial endothelial cell (GO:1904999) ISS
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 [359] ...
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • positive regulation of establishment of T cell polarity (GO:1903905) ISS
  • positive regulation of T cell migration (GO:2000406) ISS
Included in GtoImmuPdb based on its association with leukemia.
ADAM10
(M12: Astacin/Adamalysin)
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
ADAM10 has been identified as the primary physiologically relevant sheddase responsible for cleavage of , and regulation of ICOS/ICOSL-dependent immune responses [241] ...
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IC
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
  • positive regulation of chemokine production (GO:0032722) IMP
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 [74] ...
ADAM8
(M12: Astacin/Adamalysin)
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • positive regulation of cellular extravasation (GO:0002693) IBA
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
  • lymphocyte chemotaxis (GO:0048247) ISS
  • positive regulation of neutrophil extravasation (GO:2000391) IDA
  • positive regulation of fibronectin-dependent thymocyte migration (GO:2000415) ISS
  • positive regulation of eosinophil migration (GO:2000418) 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) [307] ...
Adenosine deaminase
(Adenosine turnover)
  • negative regulation of leukocyte migration (GO:0002686) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • leukocyte migration (GO:0050900) 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 ...
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 [3] ...
Arginase II
(Arginase)
  • negative regulation of macrophage inflammatory protein 1 alpha production (GO:0071641) IEA
  • negative regulation of chemokine (C-C motif) ligand 4 production (GO:0071644) IEA
  • negative regulation of chemokine (C-C motif) ligand 5 production (GO:0071650) IEA
  • negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562) IEA
The role of ARG2 in immuno-oncology is reviewed in [3] ...
Caspase 3
(C14: Caspase)
  • 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 [297] ...
cathepsin G
(S1: Chymotrypsin)
  • monocyte chemotaxis (GO:0002548) 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 ...
chitinase acidic
(Chitinases)
  • positive regulation of chemokine production (GO:0032722) IDA
AMCase has been shown to be produced during type 2 inflammatory responses [453] ...
C-terminal Src kinase
(Csk family)
  • T cell costimulation (GO:0031295) TAS
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 [398] ...
death associated protein kinase 2
(Death-associated kinase (DAPK) family)
  • positive regulation of neutrophil chemotaxis (GO:0090023) IMP
  • positive regulation of eosinophil chemotaxis (GO:2000424) IMP
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [127] ...
Ecto-5'-Nucleotidase
(Adenosine turnover)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
Via the conversion of ADP/ATP to AMP (CD39; ENTPD1) and AMP to adenosine (CD73; NT5E) these ectonucleotidase enzymes are crucial to the regulation of purinergic signals delivered to immune cells [13] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • negative regulation of chemokine production (GO:0032682) IDA
  • leukocyte migration involved in inflammatory response (GO:0002523) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
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 [386] ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • positive regulation of chemokine production (GO:0032722) ISS
Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [123] ...
FER tyrosine kinase
(Fer family)
  • diapedesis (GO:0050904) ISS
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 ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) TAS
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [301] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of leukocyte migration (GO:0002686) TAS
  • positive regulation of chemokine production (GO:0032722) TAS
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 [15] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • leukocyte migration involved in immune response (GO:0002522) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [29] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • 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 [201] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • positive regulation of leukocyte adhesion to vascular endothelial cell (GO:1904996) IMP
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 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • neutrophil migration (GO:1990266) IMP
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 [259] ...
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • 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 [263] ...
Janus kinase 2
(Janus kinase (JakA) family)
  • 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 [36,38,366] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • 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 [9] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell activation (GO:0050870) IDA
  • leukocyte migration (GO:0050900) TAS
  • positive regulation of leukocyte cell-cell adhesion (GO:1903039) IMP
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) [301] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • C-X-C chemokine receptor CXCR4 signaling pathway (GO:0038159) IMP
  • leukocyte migration (GO:0050900) TAS
  • regulation of monocyte chemotaxis (GO:0090025) IMP
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 [117,121,385] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • positive regulation of macrophage chemotaxis (GO:0010759) IGI
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 [196,247] ...
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 [120,427] ...
MMP14
(M10: Matrix metallopeptidase)
  • positive regulation of macrophage migration (GO:1905523) IEA
MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [98] ...
MMP9
(M10: Matrix metallopeptidase)
  • leukocyte migration (GO:0050900) IEA
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 [214] ...
peptidylprolyl isomerase A
(Peptidyl-prolyl cis/trans isomerases)
  • neutrophil chemotaxis (GO:0030593) IDA
  • leukocyte chemotaxis (GO:0030595) IMP
Cyclophilin A (CypA) is well known as a specific binding protein for cyclosporin A (CsA) [142] ...
phosphatase and tensin homolog
(Lipid phosphate phosphatases)
  • 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 [367] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • T cell costimulation (GO:0031295) 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)
  • mast cell chemotaxis (GO:0002551) TAS
  • T cell chemotaxis (GO:0010818) TAS
  • neutrophil chemotaxis (GO:0030593) TAS
  • natural killer cell chemotaxis (GO:0035747) TAS
  • B cell chemotaxis (GO:0035754) TAS
  • neutrophil extravasation (GO:0072672) 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 [146] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • T cell chemotaxis (GO:0010818) TAS
  • neutrophil chemotaxis (GO:0030593) TAS
  • natural killer cell chemotaxis (GO:0035747) TAS
  • neutrophil extravasation (GO:0072672) TAS
The role of PI3Kγ in immuno-oncology is reviewed in [3] ...
phosphodiesterase 4B
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • neutrophil chemotaxis (GO:0030593) ISS
  • leukocyte migration (GO:0050900) ISS
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 [407] ...
phosphodiesterase 5A
(Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs))
  • negative regulation of T cell proliferation (GO:0042130) IEA
The role of PDE5A in immuno-oncology is reviewed in [3] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • positive regulation of leukocyte migration (GO:0002687) IEA
  • myeloid leukocyte migration (GO:0097529) IEA
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 [242] ...
phosphoinositide kinase, FYVE-type zinc finger containing
(1-phosphatidylinositol-3-phosphate 5-kinase family)
  • neutrophil chemotaxis (GO:0030593) IDA
PIKfyve is a class III PI kinase. Evidence is revealing a crucial role for PIKfyve in Toll-like receptor (TLR) signaling via production of the cytokines IL-12 and IL-23 [60] ...
PLA2-G7
(Phospholipase A2, Hydrolases)
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
PLA2-G7 (also referred to as Lp-PLA2) is a pro-inflammatory enzyme. It cleaves oxidatively damaged phospholipid substrates to generate pro-inflammatory mediators including lysophosphatidylcholine and oxidized nonesterified fatty acids [245] ...
proteinase 3
(S1: Chymotrypsin)
  • neutrophil extravasation (GO:0072672) IMP
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 [205] ...
protein kinase C theta
(Delta subfamily)
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
  • 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 [21] ...
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 tyrosine kinase 2
(Fak family)
  • positive regulation of macrophage chemotaxis (GO:0010759) IGI
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [77] ...
protein tyrosine kinase 2 beta
(Fak family)
  • regulation of macrophage chemotaxis (GO:0010758) ISS
  • chemokine-mediated signaling pathway (GO:0070098) ISS
  • positive regulation of B cell chemotaxis (GO:2000538) 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 [77] ...
protein tyrosine phosphatase non-receptor type 11
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • T cell costimulation (GO:0031295) TAS
SHP2 regulates programmed cell death 1 (PD-1)-mediated signal transduction and it is therefore involved in immune checkpoint modulation.
protein tyrosine phosphatase non-receptor type 22
(Protein tyrosine phosphatases non-receptor type (PTPN))
  • negative regulation of T cell activation (GO:0050868) IMP
  • positive regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000566) IBA
PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [85] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of immature T cell proliferation in thymus (GO:0033092) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) 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) [289] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation (GO:2000452) ISS
RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [280,331,357,401] ...
sPLA2-1B
(Phospholipase A2)
  • neutrophil chemotaxis (GO:0030593) ISS
sPLA2 enzymes catalyze the first step of the arachidonic acid pathway, so are inextricably involved in the production of arachadonic acid for inflammatory mediator synthesis. Excess sPLA2 activity is suggested to contribute to several inflammatory diseases. The sPLA2-1B isozyme has been reported to induce leukotriene B4 (LTB4) production in human neutrophils, using a mechanism independent of arachadonic acid generation [217] ...
spleen associated tyrosine kinase
(Syk family)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • neutrophil chemotaxis (GO:0030593) IDA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IBA
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IMP
  • 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 [130,330] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) 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 [240] ...
tyrosine kinase 2
(Janus kinase (JakA) family)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of NK T cell proliferation (GO:0051142) IDA
TYK2 was the first member of the Janus kinase family to be identified. It associates with the cytoplasmic domain of type I and type II cytokine receptors, where it phosphorylates receptor subunits and facilitates signalling downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 via activation of STAT-dependent transcription factors. It also mediates Type I IFN-driven responses [370] ...
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 [378] ...
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) 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)
  • positive regulation of T cell differentiation (GO:0045582) IDA
  • T cell aggregation (GO:0070489) TAS
  • T cell migration (GO:0072678) TAS
  • 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 [17] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • T cell costimulation (GO:0031295) 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 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 [51,393] ...
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • positive regulation of macrophage chemotaxis (GO:0010759) IGI
  • positive regulation of chemokine production (GO:0032722) IMP
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [3] ...
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of T cell proliferation (GO:0042130) 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.
Fc fragment of IgE receptor Ig
(Fc epsilon receptors)
  • neutrophil chemotaxis (GO:0030593) IBA
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.
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of leukocyte migration (GO:0002687) IMP
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.
Granulocyte colony-stimulating factor receptor
(Prolactin receptor family)
  • neutrophil chemotaxis (GO:0030593) IEA
This nuclear receptor mediates the effects of the cytokine, colony stimulating factor 3 (CSF3). CSF3 regulates the production, differentiation, and function of granulocytes.
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
  • positive regulation of T cell migration (GO:2000406) 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)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • leukocyte migration (GO:0050900) IBA
  • leukocyte tethering or rolling (GO:0050901) IMP
  • diapedesis (GO:0050904) IEA
  • positive regulation of leukocyte tethering or rolling (GO:1903238) IEA
  • positive regulation of T cell migration (GO:2000406) IEA
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 [141] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • leukocyte cell-cell adhesion (GO:0007159) IMP
  • memory T cell extravasation (GO:0035683) IDA
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)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • neutrophil chemotaxis (GO:0030593) IDA
  • positive regulation of leukocyte adhesion to vascular endothelial cell (GO:1904996) ISS
  • neutrophil migration (GO:1990266) IMP
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 [199] ...
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • 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-12 receptor, β2 subunit
(IL-12 receptor family)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • positive regulation of NK T cell proliferation (GO:0051142) IDA
This protein is a subunit of the functional receptor heterodimer for the IL-12 cytokine.
Interleukin 17 receptor A
(IL-17 receptor family)
  • positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340) IMP
  • granulocyte chemotaxis (GO:0071621) IEA
This protein is a common subunit shared by the heterodimeric receptors for interleukins 17 (A, B , C and F) and 25.
interleukin 17 receptor C
(IL-17 receptor family)
  • granulocyte chemotaxis (GO:0071621) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of chemokine production (GO:0032722) 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 [119] ...
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 [118] ...
Interleukin 1 receptor, type I
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of neutrophil extravasation (GO:2000391) IEA
This is one of the subunits of the functional IL-1 receptor type I heterodimer.
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • 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 23 receptor
(IL-12 receptor family)
  • 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
  • negative regulation of T cell extravasation (GO:2000408) 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
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 [360] ...
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0032831) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) 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-4 receptor subunit α
(IL-2 receptor family)
  • positive regulation of chemokine production (GO:0032722) 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 [151] ...
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • monocyte chemotaxis (GO:0002548) IC
  • positive regulation of leukocyte chemotaxis (GO:0002690) TAS
  • positive regulation of chemokine production (GO:0032722) IDA
IL6R polymorphisms are associated with asthma risk [112] ...
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 [336] ...
Interleukin-7 receptor subunit α
(IL-2 receptor family)
  • positive regulation of T cell differentiation in thymus (GO:0033089) 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 [320] ...
KIT proto-oncogene, receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • mast cell chemotaxis (GO:0002551) IDA
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 [137] ...
NLRP3
(NOD-like receptor family)
  • 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 [22,248] ...
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
  • regulation of neutrophil chemotaxis (GO:0090022) 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 ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • monocyte chemotaxis (GO:0002548) NAS
RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins.
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • positive regulation of T cell proliferation (GO:0042102) ISS
  • leukocyte cell-cell adhesion (GO:0007159) IEA
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) 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 [93] ...
single Ig and TIR domain containing
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of chemokine production (GO:0032682) ISS
IL-1R8 has been identified as a natural killer (NK) cell checkpoint that is involved in regulating NK cells' anti-viral and anti-tumour effector functions [264] ...
TLR2
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [273] ...
TLR3
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR3 is an endosomal anti-viral receptor [390] ...
TLR4
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343) IMP
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [39,321] ...
TLR7
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR7 is an endosomal receptor detecting ssRNA [390] ...
TLR9
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [390] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulin like domain containing proteins)
  • positive regulation of chemokine production (GO:0032722) ISS
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • positive regulation of monocyte extravasation (GO:2000439) IMP
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
RAGE is a single chain, membrane bound immunoglobulin type protein [278,344,430] ...
B7-H3 (CD276)
(Other immune checkpoint proteins, CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [78,100] ...
BCL6 transcription repressor
(BTB (POZ) domain containing TFs)
  • positive regulation of regulatory T cell differentiation (GO:0045591) IMP
  • negative regulation of T-helper 2 cell differentiation (GO:0045629) 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 [64,72] ...
CD1d molecule
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
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 [79,422] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • leukocyte cell-cell adhesion (GO:0007159) NAS
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • B cell adhesion (GO:0097323) 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.
CD24 molecule
(CD molecules)
  • T cell costimulation (GO:0031295) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IDA
CD24 is a small GPI-anchored sialoglycoprotein that is expressed by immune cells. It is involved in B cell and T cell functions. CD24 binds to SIGLEC10 in an interaction that selectively suppresses the immune response to danger-associated molecular patterns (DAMPs). This latter action is being explo ...
CD28
(Other immune checkpoint proteins, CD molecules)
  • T cell costimulation (GO:0031295) IBA
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • 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 [6] ...
CD300a
(CD molecules)
  • negative regulation of NK T cell activation (GO:0051134) IDA
  • negative regulation of eosinophil migration (GO:2000417) IDA
CD300a is a member of the CD300 family of leucocyte surface receptors [44] ...
CD3e
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • T cell costimulation (GO:0031295) 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 [95,364] ...
CD4
(CD molecules)
  • 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 [203,399] ...
CD47
(CD molecules)
  • positive regulation of T cell activation (GO:0050870) IDA
  • positive regulation of monocyte extravasation (GO:2000439) 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 [236] ...
CD6
(CD molecules)
  • 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 [270] ...
CD74
(CD molecules)
  • positive regulation of chemokine production (GO:0032722) IMP
  • positive regulation of neutrophil chemotaxis (GO:0090023) ISS
  • positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343) ISS
  • 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 [87] ...
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
  • 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 ...
C-type lectin domain family 7 member A
(C-type lectin-like receptors (CLRs))
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IMP
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 [50] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(Other immune checkpoint proteins, CD molecules)
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
  • 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 [257] ...
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 [164] ...
immunoglobulin like domain containing receptor 2
(Other immune checkpoint proteins)
  • negative regulation of T cell activation (GO:0050868) IDA
ILDR2 has been identified as a novel inhibitory T cell immune checkpoint protein that belongs to the B7-like protein family [148] ...
LAG3 (CD223)
(Other immune checkpoint proteins, CD molecules)
  • negative regulation of regulatory T cell differentiation (GO:0045590) ISS
Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [11,135] ...
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 [88] ...
leukocyte immunoglobulin like receptor B1 (CD85j)
(CD molecules, Other immune checkpoint proteins)
  • 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 (S100A9; P06702; which also binds TLR4 and RAGE) [53] ...
MALT1 paracaspase
(Immunoglobulin like domain containing proteins)
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) ISS
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 [256] ...
NFKB inhibitor zeta
(NF-κB regulators)
  • 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 [181,192] ...
polybromo 1
(Non-enzymatic BRD containing proteins)
  • positive regulation of T cell differentiation (GO:0045582) IC
We have included PBRM1 in GtoImmuPdb as its repression has been reported to re-sensitise tumour cells with acquired resistance to immunotherapy (e.g. checkpoint blockade by anti-PD-1 or anti-CTLA-4 mAbs) to T cell-mediated attack [302] ...
RAS guanyl releasing protein 1
(EF-hand domain containing proteins)
  • positive regulation of T cell differentiation in thymus (GO:0033089) 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 [136,325,354] ...
selectin P (CD62)
(CD molecules)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • leukocyte tethering or rolling (GO:0050901) IMP
  • positive regulation of leukocyte tethering or rolling (GO:1903238) ISS
  • positive regulation of leukocyte migration (GO:0002687) IEA
Leukocytes use P-selectin/selectin P ligand binding to facilitate tethering and rolling on endothelial surfaces [260] ...
semaphorin 4D (CD100)
(CD molecules)
  • leukocyte aggregation (GO:0070486) IMP
Semaphorin 4D (Sema4D) is an important mediator of the movement and differentiation of multiple cell types, including immune cells [377,380] ...
SIRPA (CD172a)
(CD molecules, Signal regulatory proteins)
  • monocyte extravasation (GO:0035696) ISS
  • positive regulation of T cell activation (GO:0050870) IBA
  • negative regulation of macrophage inflammatory protein 1 alpha production (GO:0071641) ISS
  • negative regulation of chemokine (C-C motif) ligand 5 production (GO:0071650) ISS
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) [180,411] ...
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 T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [266] ...
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 [229] ...