Top ▲

Targets Associated to Immuno Processes - Chemotaxis & migration

Jump to: GPCR | Ion Channels | NHRs | Enzymes | Catalytic Receptors | Other Protein Targets |

Chemotaxis & migration
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ACKR1
(Chemokine receptors)
  • regulation of chemokine production (GO:0032642) IBA
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.
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 [81] ...
A2A receptor
(Adenosine receptors)
  • negative regulation of alpha-beta T cell activation (GO:0046636) IEA
A2A receptor is discussed in this immuno-oncology review [2] ...
A2B receptor
(Adenosine receptors)
  • positive regulation of chemokine production (GO:0032722) IEA
A2B receptor is discussed in this immuno-oncology review [2] ...
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
  • leukocyte migration (GO:0050900) IBA
  • 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.
C5a1 receptor
(Complement peptide receptors)
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • neutrophil chemotaxis (GO:0030593) IEA
  • leukocyte migration (GO:0050900) IBA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
C5aR is typically associated with the compement cascade and innate immunity.
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 [148] ...
CCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • 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.
CCR2
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • positive regulation of T cell chemotaxis (GO:0010820) 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
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • 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 [2] ...
CCR5
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
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 [2] ...
CCR6
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • 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) IEA
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 [103,120] ...
CCR7
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) IC
  • myeloid dendritic cell chemotaxis (GO:0002408) 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.
chemerin receptor
(Chemerin receptor)
  • positive regulation of macrophage chemotaxis (GO:0010759) IMP
The chemerin receptor is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1 ...
CXCR1
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
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 [2] ...
CXCR2
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
  • neutrophil chemotaxis (GO:0030593) 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 [2] ...
CXCR3
(Chemokine receptors)
  • regulation of leukocyte migration (GO:0002685) IEA
  • T cell chemotaxis (GO:0010818) IEA
  • chemokine (C-C motif) ligand 11 production (GO:0071954) IDA
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.
CXCR4
(Chemokine receptors)
  • dendritic cell chemotaxis (GO:0002407) TAS
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.
CXCR5
(Chemokine receptors)
  • 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.
CX3CR1
(Chemokine receptors)
  • macrophage chemotaxis (GO:0048246) 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 [215] ...
FFA2 receptor
(Free fatty acid receptors)
  • leukocyte chemotaxis involved in inflammatory response (GO:0002232) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
FFA2 is a GPCR activated by short-chain fatty acids, and evidence suggests that FFA2 (and FFA3) mediate beneficial effects associated with a fiber-rich diet. These GPCRs are of interest as targets for the treatment of inflammatory and metabolic diseases. FFA2 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 ...
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 [30] ...
FPR1
(Formylpeptide receptors)
  • leukocyte migration (GO:0050900) IBA
The primary function of FPR1 is recognition of formylpeptides including bacterial formylpeptides, so it is therefore a component of the host defense mechanism.
FPR2/ALX
(Formylpeptide receptors)
  • leukocyte migration (GO:0050900) 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. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
FPR2/ALX
(Formylpeptide receptors)
  • leukocyte migration (GO:0050900) 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. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
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 alleric 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 [72,142] ...
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 [98,158] ...
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 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
  • chemokine (C-C motif) ligand 2 secretion (GO:0035926) IDA
  • leukocyte migration (GO:0050900) IDA
  • chemokine secretion (GO:0090195) IDA
  • negative regulation of chemokine secretion (GO:0090198) 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) [65] ...
S1P1 receptor
(Lysophospholipid (S1P) receptors)
  • leukocyte chemotaxis (GO:0030595) IEA
  • T cell migration (GO:0072678) ISS
S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [85-86,172] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
TRPM2
(Transient Receptor Potential channels)
  • 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 [155] ...
TRPM4
(Transient Receptor Potential channels)
  • dendritic cell chemotaxis (GO:0002407) ISS
Expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [155] ...
TRPV4
(Transient Receptor Potential channels)
  • 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 [155] ...
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) [174] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
3-phosphoinositide dependent protein kinase 1
(PDK1 family)
  • T cell costimulation (GO:0031295) TAS
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 [97] ...
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 [36] ...
ADAM8
(M12: Astacin/Adamalysin)
  • leukocyte migration involved in inflammatory response (GO:0002523) ISS
  • 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) [157] ...
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
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 ...
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • regulation of T cell differentiation (GO:0045580) IEA
BRAFV600E- immuno-oncology [2] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • regulation of T cell differentiation in thymus (GO:0033081) TAS
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [104] ...
Caspase 3
(C14: Caspase)
  • negative regulation of activated T cell proliferation (GO:0046007) IEA
Defective caspase 3 expression in immune effector cells my influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [151] ...
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 [197] ...
death associated protein kinase 2
(Death-associated kinase (DAPK) family)
  • positive regulation of neutrophil chemotaxis (GO:0090023) IMP
  • neutrophil migration (GO:1990266) IEA
  • positive regulation of eosinophil chemotaxis (GO:2000424) IMP
DAPk2 is recognised as a regulator of apoptosis, autophagy and inflammation [66] ...
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 [9] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • leukocyte migration involved in inflammatory response (GO:0002523) IEA
  • negative regulation of chemokine biosynthetic process (GO:0045079) IDA
  • 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 e ...
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 [64] ...
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 [154] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of leukocyte migration (GO:0002686) TAS
  • positive regulation of chemokine biosynthetic process (GO:0045080) 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 [11] ...
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 [21] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • negative regulation of T cell proliferation (GO:0042130) IEA
Accumulating evidence indicates that the IDO1-aryl hydrocarbon receptor (AhR, a receptor for l-kynurenine, a product of IDO1 catalysis; AHR; P35869) pathway contributes to immune homeostasis by promoting modulation of innate and adaptive immune responses. IDO1 expression can be increased by IFN-γ and IL-6 [114] ...
INPP5D
(Inositol polyphosphate phosphatases)
  • leukocyte migration (GO:0050900) TAS
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [143,183] ...
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 [131] ...
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 [132] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) ISS
  • negative regulation of T cell activation (GO:0050868) ISS
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [5] ...
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
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) [154] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • 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 [61,63,192] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • positive regulation of T cell activation (GO:0050870) IC
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [46,171] ...
MMP1
(M10: Matrix metallopeptidase)
  • leukocyte migration (GO:0050900) TAS
Overexpression of MMP-1 degrades extracellular matrix causing damage to the colon mucosa in patients with ulcerative colitis. The MMP-1 promotes secretion of TNFα causing futher damage. Levels of MMP-1 and TNFα correlate with disease severity [204] ...
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.
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 [111] ...
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • T cell costimulation (GO:0031295) 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 [48] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • T cell costimulation (GO:0031295) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [147] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) TAS
PI3Kα is priomarily 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 alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) TAS
PI3Kα is priomarily 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)
  • 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
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • 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
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • 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 PIK3CG in immuno-oncology is reviewed in [2] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • 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 PIK3CG in immuno-oncology is reviewed in [2] ...
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 [2] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • T cell costimulation (GO:0031295) TAS
  • leukocyte migration (GO:0050900) TAS
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 [124] ...
PLA2-G7
(Phospholipase A2)
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
Included in Guide to Immunopharmacology because of the association of PLA2G7 polymorphisms with atopy and asthma [107] ...
PLA2-G7
(Phospholipase A2)
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
Included in Guide to Immunopharmacology because of the association of PLA2G7 polymorphisms with atopy and asthma [107] ...
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • leukocyte migration (GO:0050900) 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 [69,170] ...
protein kinase C theta
(Delta subfamily)
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [16] ...
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 beta
(Fak family)
  • regulation of macrophage chemotaxis (GO:0010758) 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 [38] ...
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 (GO:0033091) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) 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) [146] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of activated T cell proliferation (GO:0046006) ISS
  • regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation (GO:2000452) ISS
RIPK1 and RIPK3 are involved in necroptosis [165,177,199] ...
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 [112] ...
spleen associated tyrosine kinase
(Syk family)
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • neutrophil chemotaxis (GO:0030593) IDA
  • positive regulation of gamma-delta T cell differentiation (GO:0045588) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IBA
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 [68,164] ...
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 [123] ...
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
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • T cell aggregation (GO:0070489) TAS
  • T cell migration (GO:0072678) TAS
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [12] ...
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) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
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 pathogenesis ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of T cell differentiation (GO:0045582) IEA
A co-stimulatory immune checkpoint molecule. Endogenous ligand is CD70. Interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1).
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • positive regulation of chemokine secretion (GO:0090197) 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 [2] ...
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.
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
herpes virus entry mediator
(Tumour necrosis factor (TNF) receptor family)
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of alpha-beta T cell proliferation (GO:0046642) IEA
  • positive regulation of T cell migration (GO:2000406) IEA
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.
herpes virus entry mediator
(Tumour necrosis factor (TNF) receptor family)
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of alpha-beta T cell proliferation (GO:0046642) IEA
  • positive regulation of T cell migration (GO:2000406) IEA
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) TAS
  • 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 [73] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • leukocyte cell-cell adhesion (GO:0007159) IMP
  • leukocyte migration (GO:0050900) TAS
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 migration involved in inflammatory response (GO:0002523) IEA
  • leukocyte cell-cell adhesion (GO:0007159) IDA
  • neutrophil chemotaxis (GO:0030593) IDA
  • cellular extravasation (GO:0045123) IEA
  • leukocyte migration (GO:0050900) TAS
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). These integrins are essential for leukocyte extravasion to sites of infection. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [102] ...
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of activated T cell proliferation (GO:0042104) IDA
  • positive regulation of memory T cell differentiation (GO:0043382) ISS
  • 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 17 receptor A
(IL-17 receptor family)
  • 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 secretion (GO:0090197) 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 [62] ...
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.
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) IC
  • 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 T-helper 17 cell lineage commitment (GO:2000330) ISS
This is one of the subunits of the functional IL-23 receptor heterodimer.
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
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.
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • negative regulation of T-helper 1 cell differentiation (GO:0045626) IEA
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) IEA
  • positive regulation of chemokine secretion (GO:0090197) 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 [76] ...
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 [58] ...
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.
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.
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 [71] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • leukocyte migration (GO:0050900) TAS
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [23,202] ...
NLRP10
(NOD-like receptor family)
  • dendritic cell migration (GO:0036336) ISS
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [87] ...
NLRP3
(NOD-like receptor family)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) IEA
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. 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 rilonacept, anakinra and canakinumab [17] ...
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).
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
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 [47] ...
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • leukocyte migration (GO:0050900) TAS
In inflammation, angiopoietin-2 (ANG2) antagonism of TIE2 initiates a positive feedback loop via forkhead box O1 (FOXO1) activation, which drives further ANG2 expression and enhances vascular remodeling and leakage [100] ...
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 [138] ...
TLR3
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of chemokine biosynthetic process (GO:0045080) IEA
TLR3 is an endosomal anti-viral receptor [194] ...
TLR4
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [25,162] ...
TLR7
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
TLR7 is an endosomal receptor detecting ssRNA [194] ...
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 [194] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
advanced glycosylation end-product specific receptor
(Immunoglobulins)
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
  • regulation of CD4-positive, alpha-beta T cell activation (GO:2000514) IDA
RAGE is a single chain, membrane bound immunoglobulin type protein [141,173,212] ...
B7-H3 (CD276)
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
B7-H3 is a costimulatory molecule for T cell activation and IFN-γ production [39,51] ...
B7-H3 (CD276)
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
B7-H3 is a costimulatory molecule for T cell activation and IFN-γ production [39,51] ...
CD2
(CD molecules)
  • regulation of T cell differentiation (GO:0045580) NAS
  • leukocyte migration (GO:0050900) TAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [213] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • leukocyte cell-cell adhesion (GO:0007159) NAS
  • 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.
CD28
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of regulatory T cell differentiation (GO:0045589) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) 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 [4] ...
CD28
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of regulatory T cell differentiation (GO:0045589) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) 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 [4] ...
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 [28] ...
CD3e
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [49,179] ...
CD47
(CD molecules)
  • positive regulation of T cell activation (GO:0050870) IDA
  • leukocyte migration (GO:0050900) TAS
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 immunesurveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [122] ...
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 [137] ...
CD66e (CEACAM5)
(CD molecules)
  • leukocyte migration (GO:0050900) TAS
CD66e is included in GtoImmuPdb because of its role in pathogen recognition.
CD74
(CD molecules)
  • negative regulation of T cell differentiation (GO:0045581) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • leukocyte migration (GO:0050900) TAS
  • positive regulation of neutrophil chemotaxis (GO:0090023) ISS
  • positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343) ISS
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 [43] ...
CD80
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
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 ...
CD80
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) NAS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
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
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • 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 ...
CD86
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • positive regulation of activated T cell proliferation (GO:0042104) IEA
  • 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 ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
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 [130] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • negative regulation of regulatory T cell differentiation (GO:0045590) IDA
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 [130] ...
Fc fragment of IgE receptor Ig
(Fc epsilon receptors)
  • neutrophil chemotaxis (GO:0030593) IBA
  • leukocyte migration (GO:0050900) TAS
ICOS (CD278)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
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 major regulator of the adaptive immune reponse that is structurally and functionally related to CD28 [83] ...
ICOS (CD278)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
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 major regulator of the adaptive immune reponse that is structurally and functionally related to CD28 [83] ...
LAG3 (CD223)
(CD molecules)
  • negative regulation of T cell activation (GO:0050868) IEA
LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [7] ...
LAG3 (CD223)
(CD molecules)
  • negative regulation of T cell activation (GO:0050868) IEA
LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [7] ...
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 [44] ...
programmed cell death 1 (CD279)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
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 [153] ...
programmed cell death 1 (CD279)
(CD molecules)
  • T cell costimulation (GO:0031295) TAS
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 [153] ...
semaphorin 4D (CD100)
(CD molecules)
  • leukocyte aggregation (GO:0070486) IMP
Semaphorin 4D is an important mediator of the movement and differentiation of multiple cell types, including immune cells [187-188] ...
SIRPA (CD172a)
(CD molecules)
  • leukocyte migration (GO:0050900) TAS
Pharmacological agents which block the SIRPα/CD47 antiphagocytic axis are being investigated as potential immuno-oncology therapeutics which would act to promote immunosurveillance and increase phagocytosis of cancer cells by tumour associated macrophages (TAMs). Specifically, the anti-SIPRα monoclonal antibody OSE-172 (Effi-DEM) is in early stage development (OSE IMMUNOTherapeutics), and proof of concept has been demonstrated in in vivo models. Preclinical testing suggests that the therapeutic effect of OSE-172 is observed in both monotherapy or when combined with other checkpoint inhibitors, or with immune system stimulators. Anti-CD47 antibodies are also in early stage development, as reported by Gholamin et al. (2017) [67] ...
TIGIT
(Immunoglobulins)
  • 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 ...
TIGIT
(Immunoglobulins)
  • 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)
(CD molecules)
  • 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
  • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [134] ...
TIM3 (CD366)
(CD molecules)
  • 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
  • negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [134] ...