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Targets Associated to Immuno Processes - Immune regulation

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Immune regulation
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ADGRE2
(Adhesion Class GPCRs)
  • regulation of mast cell degranulation (GO:0043304) IMP
ADGRE2 is included in GtoImmuPdb because its tissue expression profile and its ability to activate secretion of inflammatory cytokines (IL-8, TNF) by monocytes and macrophages [122] ...
A2A receptor
(Adenosine receptors)
  • negative regulation of alpha-beta T cell activation (GO:0046636) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
A2A receptor is discussed in this immuno-oncology review [2] ...
A2B receptor
(Adenosine receptors)
  • positive regulation of chronic inflammatory response to non-antigenic stimulus (GO:0002882) IEA
  • positive regulation of mast cell degranulation (GO:0043306) 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)
  • complement component C3a receptor activity (GO:0004876) IBA
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • regulation of complement activation (GO:0030449) TAS
  • 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)
  • complement component C5a receptor activity (GO:0004878) IDA
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • regulation of complement activation (GO:0030449) TAS
  • positive regulation of neutrophil chemotaxis (GO:0090023) IEA
C5aR is typically associated with the compement cascade and innate immunity.
C5a2 receptor
(Complement peptide receptors)
  • complement component C5a receptor activity (GO:0004878) IBA
  • regulation of complement activation (GO:0030449) TAS
  • 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.
CB1 receptor
(Cannabinoid receptors)
  • positive regulation of acute inflammatory response to antigenic stimulus (GO:0002866) IEA
  • positive regulation of fever generation (GO:0031622) IEA
  • negative regulation of mast cell activation (GO:0033004) IEA
CB1 receptor is involved in controlling mast cell degranulation and maturation [275] ...
CB2 receptor
(Cannabinoid receptors)
  • negative regulation of mast cell activation (GO:0033004) IEA
  • negative regulation of inflammatory response (GO:0050728) 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 [217] ...
CCR1
(Chemokine receptors)
  • positive regulation of osteoclast differentiation (GO:0045672) IMP
  • 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)
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
  • negative regulation of type 2 immune response (GO:0002829) ISS
  • positive regulation of T cell chemotaxis (GO:0010820) ISS
  • negative regulation of eosinophil degranulation (GO:0043310) ISS
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) ISS
  • positive regulation of inflammatory response (GO:0050729) ISS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
  • positive regulation of immune complex clearance by monocytes and macrophages (GO:0090265) 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 [2] ...
CCR6
(Chemokine receptors)
  • 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 [154,174] ...
CCR7
(Chemokine receptors)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • positive regulation of hypersensitivity (GO:0002885) ISS
  • positive regulation of humoral immune response (GO:0002922) ISS
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
  • positive regulation of neutrophil chemotaxis (GO:0090023) IDA
  • positive regulation of dendritic cell chemotaxis (GO:2000510) ISS
  • positive regulation of immunological synapse formation (GO:2000522) 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 ...
CXCR3
(Chemokine receptors)
  • regulation of leukocyte migration (GO:0002685) 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.
CX3CR1
(Chemokine receptors)
  • negative regulation of chronic inflammatory response to non-antigenic stimulus (GO:0002881) 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.
EP3 receptor
(Prostanoid receptors)
  • positive regulation of fever generation (GO:0031622) ISS
Foudi et al. (2012) [93] ...
EP4 receptor
(Prostanoid receptors)
  • negative regulation of inflammatory response (GO:0050728) IDA
  • positive regulation of inflammatory response (GO:0050729) ISS
  • 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 [320] ...
FFA2 receptor
(Free fatty acid receptors)
  • regulation of acute inflammatory response (GO:0002673) ISS
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • cell surface pattern recognition receptor signaling pathway (GO:0002752) IMP
  • positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879) 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 cytokine production involved in immune response (GO:0002720) ISS
  • positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879) ISS
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [43] ...
FPR1
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
The primary function of FPR1 is recognition of formylpeptides including bacterial formylpeptides, so it is therefore a component of the host defense mechanism.
FPR2/ALX
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
Formyl peptide receptor type 2 ( (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
FPR2/ALX
(Formylpeptide receptors)
  • complement receptor mediated signaling pathway (GO:0002430) IBA
  • complement receptor activity (GO:0004875) IBA
Formyl peptide receptor type 2 ( (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. FPR2/ALX receptor agonism is a new therapeutic concept to treat inflammatory conditions.
GPR183
(Class A Orphans)
  • positive regulation of B cell proliferation (GO:0030890) IDA
  • dendritic cell homeostasis (GO:0036145) ISS
Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [144,230] ...
MAS1
(Class A Orphans)
  • regulation of inflammatory response (GO:0050727) IEA
Experimental evidence from animal studies suggest a role for MAS1 in the anti-inflammatory pathway mediated by angiotensin-(1-7) [70,87] ...
NK1 receptor
(Tachykinin receptors)
  • positive regulation of leukocyte migration (GO:0002687) IEA
  • positive regulation of lymphocyte proliferation (GO:0050671) IEA
Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
PAF receptor
(Platelet-activating factor receptor)
  • lipopolysaccharide receptor activity (GO:0001875) IEA
  • positive regulation of neutrophil degranulation (GO:0043315) 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
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
  • positive regulation of toll-like receptor 2 signaling pathway (GO:0034137) IMP
  • negative regulation of toll-like receptor 3 signaling pathway (GO:0034140) IMP
  • positive regulation of toll-like receptor 3 signaling pathway (GO:0034141) IMP
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • positive regulation of eosinophil degranulation (GO:0043311) IDA
  • positive regulation of neutrophil mediated killing of gram-negative bacterium (GO:0070963) 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) [98] ...
Ion Channels
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
P2X7
(P2X receptors)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) IEA
  • T cell homeostasis (GO:0043029) IEA
The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [176,240] ...
TRPM4
(Transient Receptor Potential channels)
  • regulation of T cell cytokine production (GO:0002724) IDA
Expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [225] ...
TRPV4
(Transient Receptor Potential channels)
  • positive regulation of macrophage chemotaxis (GO:0010759) IEA
  • positive regulation of inflammatory response (GO:0050729) IEA
Expressed on mouse neutrophils [225] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • toll-like receptor 4 signaling pathway (GO:0034142) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • negative regulation of inflammatory response (GO:0050728) 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) [255] ...
Liver X receptor-α
(1H. Liver X receptor-like receptors)
  • positive regulation of toll-like receptor 4 signaling pathway (GO:0034145) IDA
  • negative regulation of macrophage activation (GO:0043031) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses- drug target for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [312] ...
Liver X receptor-β
(1H. Liver X receptor-like receptors)
  • negative regulation of interferon-gamma-mediated signaling pathway (GO:0060336) NAS
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses- drug target for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [312] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
3-phosphoinositide dependent protein kinase 1
(PDK1 family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • regulation of mast cell degranulation (GO:0043304) IEA
  • T cell receptor signaling pathway (GO:0050852) 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 [141] ...
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • B-1 B cell homeostasis (GO:0001922) IEA
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • B cell receptor signaling pathway (GO:0050853) IEA
Included in GtoImmuPdb based on its association with leukemia.
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of leukocyte chemotaxis (GO:0002690) IC
  • positive regulation of T cell chemotaxis (GO:0010820) IMP
  • regulation of mast cell apoptotic process (GO:0033025) ISS
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [52] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of acute inflammatory response (GO:0002675) ISS
  • positive regulation of T cell differentiation in thymus (GO:0033089) ISS
  • activation of MAPK activity involved in innate immune response (GO:0035419) 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) [229] ...
Adenosine deaminase
(Adenosine turnover)
  • positive regulation of germinal center formation (GO:0002636) IEA
  • negative regulation of leukocyte migration (GO:0002686) IEA
  • negative regulation of mature B cell apoptotic process (GO:0002906) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of T cell differentiation in thymus (GO:0033089) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) IEA
Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting ...
BLK proto-oncogene, Src family tyrosine kinase
(Src family)
  • B cell receptor signaling pathway (GO:0050853) IDA
BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [283] ...
B-Raf proto-oncogene, serine/threonine kinase
(RAF family)
  • regulation of T cell differentiation (GO:0045580) IEA
  • T cell receptor signaling pathway (GO:0050852) IEA
BRAFV600E- immuno-oncology [2] ...
Bruton tyrosine kinase
(Tec family)
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • regulation of B cell cytokine production (GO:0002721) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of B cell differentiation (GO:0045579) TAS
  • B cell receptor signaling pathway (GO:0050853) TAS
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [32] ...
calcium/calmodulin dependent protein kinase IV
(CAMK1 family)
  • regulation of T cell differentiation in thymus (GO:0033081) TAS
  • regulation of osteoclast differentiation (GO:0045670) TAS
CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [155] ...
Caspase 3
(C14: Caspase)
  • B cell homeostasis (GO:0001782) IEA
  • erythrocyte differentiation (GO:0030218) IDA
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • T cell homeostasis (GO:0043029) IEA
  • 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 [220] ...
Caspase 8
(C14: Caspase)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of macrophage differentiation (GO:0045651) IMP
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Roles of apoptotic caspases extending beyond cell death, for example, mediating cellular immune processes such as inflammasome modulation, necroptosis and pro-inflammatory cytokine processing have been reported [187] ...
cathepsin B
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin G
(S1: Chymotrypsin)
  • positive regulation of immune response (GO:0050778) IEA
Cathepsin G is a leukocyte serine protease of the chymotrypsin family, related to neutrophil elastase and the granzymes. It is stored in azurophil granules and acts intracellularly to degrade ingested host pathogens and axtracellularly to breakdown ECM components at sites of inflammation. Cathepsin ...
cathepsin H
(C1: Papain)
  • immune response-regulating signaling pathway (GO:0002764) IDA
Cathepsin H may act as a pro-granzyme B convertase [69] ...
cathepsin L
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics.
cathepsin S
(C1: Papain)
  • toll-like receptor signaling pathway (GO:0002224) TAS
Due to its role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression. Cathepsin S inhibitors are being investigated for clinical efficacy in inflammatory conditions- e.g. RG7625 (Roche) in celiac disease (Phase 1) and Sjogren's syndrome (Phase 2).
complement C1r
(S1: Chymotrypsin)
  • complement activation (GO:0006956) TAS
  • complement activation, classical pathway (GO:0006958) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the C1-complex of the classical complement pathway.
complement C1s
(S1: Chymotrypsin)
  • complement activation, lectin pathway (GO:0001867) IBA
  • complement activation (GO:0006956) TAS
  • complement activation, classical pathway (GO:0006958) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the C1-complex of the classical complement pathway.
complement factor B
(S1: Chymotrypsin)
  • complement activation (GO:0006956) TAS
  • complement activation, alternative pathway (GO:0006957) TAS
  • regulation of complement activation (GO:0030449) TAS
A protease component of the alternative complement pathway. Cleaved by complement factor D ...
complement factor D
(3.4.21.46 Complement factor D)
  • complement activation (GO:0006956) TAS
  • complement activation, alternative pathway (GO:0006957) TAS
A protease component of the alternative complement pathway; responsible for cleaving complement factor B ...
conserved helix-loop-helix ubiquitous kinase
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Ikkα is one of the catalytic subunits of the IκB kinase (IKK) complex, an upstream component of the NF-κB signal transduction cascade; NF-κB signaling being involved in propagating the cellular response to inflammation. IKK frees NF-κB from its inhibitory interaction with IκBα (inhibitor of kappa B), allowing NF-κB translocation to the nucleus where it modulates transcriptional activity. Additional functions of Ikkα beyond NF-κB activation are reviewed in [121] ...
COX-2
(Cyclooxygenase)
  • positive regulation of fever generation (GO:0031622) ISS
  • regulation of inflammatory response (GO:0050727) NAS
The cyclooxygenase enzymes are included in GtoImmuPdb as they are involved in the production of inflammatory mediators, and are long-standing anti-inflammatory drug targets. The role of COX-2 in immuno-oncology is reviewed in [2] ...
C-terminal Src kinase
(Csk family)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368) IBA
CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [294] ...
cyclin dependent kinase 6
(CDK4 subfamily)
  • negative regulation of myeloid cell differentiation (GO:0045638) IDA
  • regulation of erythrocyte differentiation (GO:0045646) IMP
  • negative regulation of monocyte differentiation (GO:0045656) IDA
  • regulation of hematopoietic stem cell differentiation (GO:1902036) IEA
Phenotypic abnormalities in CDK6 knockout mice suggest biological roles in addition to mitotic cell cycle regulation. Alternate roles include involvement in hematopoietic function and inhibition of T cell differentiation [106,227] ...
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 [100] ...
DNA-dependent protein kinase catalytic subunit
(Other PIKK family kinases)
  • negative regulation of immunoglobulin production (GO:0002638) IEA
  • positive regulation of immune system process (GO:0002684) IEA
Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ...
Ecto-5'-Nucleotidase
(Adenosine turnover)
  • negative regulation of inflammatory response (GO:0050728) IEA
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 [11] ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • negative regulation of inflammatory response (GO:0050728) NAS
  • positive regulation of immune response (GO:0050778) 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 e ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • regulation of hematopoietic progenitor cell differentiation (GO:1901532) ISS
  • regulation of hematopoietic stem cell proliferation (GO:1902033) ISS
  • regulation of hematopoietic stem cell differentiation (GO:1902036) 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 [97] ...
eukaryotic translation initiation factor 2 alpha kinase 4
(GCN2 subfamily)
  • positive regulation of defense response to virus by host (GO:0002230) ISS
  • positive regulation of adaptive immune response (GO:0002821) ISS
GCN2 is a so-called 'stress kinase'. It phosphorylates serine 51 on the global transcription factor eIF2α upon activation by uncharged tRNA; tRNAs accumulate when amino acid levels are depleted. Phospho-eIF2α blocks translation to cause proliferative arrest.

GCN2 plays several roles in the immune system. It is required for dendritic cell activation and antigen presentation. The GCN2 stress response is required for both optimal proliferation of CD8+ T cells after antigen stimulation, and trafficking to lymphoid organs, i.e. for normal cytotoxic T cell function [292] ...
FER tyrosine kinase
(Fer family)
  • negative regulation of mast cell activation involved in immune response (GO:0033007) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) ISS
  • regulation of mast cell degranulation (GO:0043304) IBA
FER acts downstream of the activated high affinity immunoglobulin epsilon receptor (FCεR1) and plays a role in FCεR1-mediated signaling in mast cells, regulation of mast cell degranulation, leukocyte recruitment, and leukocyte extravasation following bacterial lipopolysaccharide (LPS ...
FGR proto-oncogene, Src family tyrosine kinase
(Src family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) ISS
  • regulation of innate immune response (GO:0045088) ISS
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [26] ...
FYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) IDA
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [224] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of leukocyte migration (GO:0002686) TAS
  • negative regulation of mast cell cytokine production (GO:0032764) IEA
  • erythrocyte homeostasis (GO:0034101) IMP
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

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

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [13] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • innate immune response-activating signal transduction (GO:0002758) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of inflammatory response (GO:0050727) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [26] ...
IL2 inducible T-cell kinase
(Tec family)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [32] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • positive regulation of T cell tolerance induction (GO:0002666) IEA
  • positive regulation of chronic inflammatory response (GO:0002678) IEA
  • positive regulation of type 2 immune response (GO:0002830) IEA
  • 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 [165] ...
Inducible NOS
(Nitric oxide synthases)
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
The role of iNOS in immuno-oncology is reviewed in [2] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [3,30,36,263] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
IKKε is the only inducible IKK family member. Expression is induced in response to LPS, viral infection and several cytokines. IKKε expression is restricted to pancreas, thymus, spleen and peripheral blood leukocytes. This is in contrast to all other IKK family kinases which are cons ...
INPP5D
(Inositol polyphosphate phosphatases)
  • negative regulation of B cell proliferation (GO:0030889) IEA
  • positive regulation of B cell differentiation (GO:0045579) IEA
  • positive regulation of erythrocyte differentiation (GO:0045648) IEA
  • negative regulation of monocyte differentiation (GO:0045656) IEA
  • negative regulation of neutrophil differentiation (GO:0045659) IEA
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
  • negative regulation of immune response (GO:0050777) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [212,271] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 2 signaling pathway (GO:0034134) IMP
  • toll-like receptor 4 signaling pathway (GO:0034142) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
interleukin 1 receptor associated kinase 2
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of macrophage tolerance induction (GO:0010933) ISS
  • negative regulation of macrophage cytokine production (GO:0010936) ISS
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
IRAK4 is essential for most innate immune responses to bacteria and viruses, and IRAK4 deficiency (caused by mutations) has been shown to result in recurrent invasive pneumococcal disease [194] ...
IP3 kinase B
(Inositol 1,4,5-trisphosphate 3-kinases)
  • myeloid cell homeostasis (GO:0002262) IEA
  • negative regulation of neutrophil apoptotic process (GO:0033030) IEA
  • negative regulation of myeloid cell differentiation (GO:0045638) IEA
  • positive regulation of alpha-beta T cell differentiation (GO:0046638) IEA
IP3 kinase B (ITPKB) as an essential mediator of T cell activation, whose inhibition is considered a novel approach to treat autoimmune disease [197] ...
Janus kinase 1
(Janus kinase (JakA) family)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
The JAK1 tyrosine kinase is crucial for signaling of certain type I and type II cytokines, via receptors belonging to the IL-2, IL-4 and IL-6 receptor families as well as neurotrophin-1 and leptin receptors (all type I cytokine receptors). JAK1 is also involved in signalling via type I ...
Janus kinase 2
(Janus kinase (JakA) family)
  • erythrocyte differentiation (GO:0030218) ISS
  • regulation of inflammatory response (GO:0050727) IDA
  • positive regulation of inflammatory response (GO:0050729) IEA
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [272] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • negative regulation of dendritic cell cytokine production (GO:0002731) ISS
  • erythrocyte differentiation (GO:0030218) IBA
  • positive regulation of T cell proliferation (GO:0042102) IBA
  • T cell homeostasis (GO:0043029) ISS
  • 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 [7] ...
LCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of T cell receptor signaling pathway (GO:0050862) NAS
  • positive regulation of T cell activation (GO:0050870) IDA
  • regulation of lymphocyte activation (GO:0051249) NAS
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [224] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • B cell homeostasis (GO:0001782) ISS
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) ISS
  • negative regulation of myeloid leukocyte differentiation (GO:0002762) IEA
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) ISS
  • Fc receptor mediated inhibitory signaling pathway (GO:0002774) ISS
  • erythrocyte differentiation (GO:0030218) ISS
  • negative regulation of B cell proliferation (GO:0030889) IBA
  • T cell costimulation (GO:0031295) TAS
  • regulation of mast cell activation (GO:0033003) ISS
  • negative regulation of toll-like receptor 2 signaling pathway (GO:0034136) ISS
  • negative regulation of toll-like receptor 4 signaling pathway (GO:0034144) ISS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of mast cell degranulation (GO:0043304) ISS
  • regulation of erythrocyte differentiation (GO:0045646) ISS
  • regulation of inflammatory response (GO:0050727) IEA
  • negative regulation of immune response (GO:0050777) TAS
  • B cell receptor signaling pathway (GO:0050853) IEA
  • regulation of B cell receptor signaling pathway (GO:0050855) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IEA
  • positive regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060369) IEA
  • 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 [94,96,287] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) IEA
  • B cell receptor signaling pathway (GO:0050853) IEA
In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [148,183] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • positive regulation of T cell cytokine production (GO:0002726) IMP
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of T cell activation (GO:0050870) IC
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [71,252] ...
MMP12
(M10: Matrix metallopeptidase)
  • regulation of defense response to virus by host (GO:0050691) IEA
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target.
MMP14
(M10: Matrix metallopeptidase)
  • positive regulation of B cell differentiation (GO:0045579) ISS
  • 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.
MMP2
(M10: Matrix metallopeptidase)
  • positive regulation of innate immune response (GO:0045089) IEA
MMP2 is included in GtoImmuPdb based on its potential involvement in asthma.
otulin
(C101: OTULIN peptidase)
  • negative regulation of inflammatory response (GO:0050728) IMP
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IMP
Otulin is reported as a negative regulator of inflammation and autoimmunity [73] ...
p21 (RAC1) activated kinase 1
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) 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 [74] ...
p21 (RAC1) activated kinase 2
(PAKA subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Pharmacological inhibition of PAK2 has immunosuppressive effects [216] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) 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
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) 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)
  • positive regulation of neutrophil apoptotic process (GO:0033031) IMP
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) 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)
  • positive regulation of neutrophil apoptotic process (GO:0033031) IMP
  • T cell receptor signaling pathway (GO:0050852) TAS
  • B cell receptor signaling pathway (GO:0050853) 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)
  • positive regulation of acute inflammatory response (GO:0002675) IEA
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)
  • positive regulation of acute inflammatory response (GO:0002675) IEA
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
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • negative regulation of osteoclast differentiation (GO:0045671) IEA
  • T cell receptor signaling pathway (GO:0050852) 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 [181] ...
PLA2-G7
(Phospholipase A2)
  • positive regulation of inflammatory response (GO:0050729) TAS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
Included in Guide to Immunopharmacology because of the association of PLA2G7 polymorphisms with atopy and asthma [158] ...
PLA2-G7
(Phospholipase A2)
  • positive regulation of inflammatory response (GO:0050729) TAS
  • positive regulation of monocyte chemotaxis (GO:0090026) IDA
Included in Guide to Immunopharmacology because of the association of PLA2G7 polymorphisms with atopy and asthma [158] ...
PLCγ1
(Phosphoinositide-specific phospholipase C)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [103,251] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • T cell receptor signaling pathway (GO:0050852) ISS
  • B cell receptor signaling pathway (GO:0050853) ISS
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 [103,251] ...
proteasome subunit beta 8
(T1: Proteasome)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
PSMB8 is a component of the immunoproteasome [92] ...
protein kinase C alpha
(Delta subfamily)
  • positive regulation of macrophage differentiation (GO:0045651) ISS
PKCα is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C beta
(Alpha subfamily)
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of B cell receptor signaling pathway (GO:0050861) ISS
PKCβ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • negative regulation of inflammatory response (GO:0050728) IC
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C epsilon
(Eta subfamily)
  • TRAM-dependent toll-like receptor 4 signaling pathway (GO:0035669) ISS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
PKCε is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C eta
(Eta subfamily)
  • positive regulation of B cell receptor signaling pathway (GO:0050861) IMP
PKCη is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • T cell receptor signaling pathway (GO:0050852) TAS
  • positive regulation of T cell activation (GO:0050870) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • positive regulation of T-helper 2 cell activation (GO:2000570) ISS
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [18] ...
protein kinase C zeta
(Iota subfamily)
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein kinase N1
(Protein kinase N (PKN) family)
  • B cell homeostasis (GO:0001782) IEA
  • regulation of germinal center formation (GO:0002634) IEA
  • regulation of immunoglobulin production (GO:0002637) IEA
  • negative regulation of B cell proliferation (GO:0030889) IEA
Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [111] ...
protein tyrosine kinase 2
(Fak family)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [55] ...
protein tyrosine kinase 2 beta
(Fak family)
  • regulation of macrophage chemotaxis (GO:0010758) ISS
  • negative regulation of myeloid cell differentiation (GO:0045638) IMP
  • 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 [55] ...
RAB27A, member RAS oncogene family
(RAB subfamily)
  • complement-dependent cytotoxicity (GO:0097278) IMP
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [135] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • positive regulation of macrophage differentiation (GO:0045651) IMP
RIPK1 and RIPK3 are involved in necroptosis [243,261,296] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of immature T cell proliferation (GO:0033091) IEA
  • toll-like receptor 2 signaling pathway (GO:0034134) IDA
  • toll-like receptor 4 signaling pathway (GO:0034142) IEA
  • positive regulation of T-helper 1 cell differentiation (GO:0045627) IEA
  • positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
  • T cell receptor signaling pathway (GO:0050852) ISS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427) IEA
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
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) [215] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of T cell mediated cytotoxicity (GO:0001914) ISS
  • regulation of adaptive immune response (GO:0002819) ISS
  • T cell homeostasis (GO:0043029) ISS
  • regulation of activated T cell proliferation (GO:0046006) ISS
  • regulation of activation-induced cell death of T cells (GO:0070235) ISS
  • regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation (GO:2000452) ISS
RIPK1 and RIPK3 are involved in necroptosis [243,261,296] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • positive regulation of adaptive immune response (GO:0002821) IDA
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [58] ...
sPLA2-1B
(Phospholipase A2)
  • positive regulation of immune response (GO:0050778) 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 [163] ...
spleen associated tyrosine kinase
(Syk family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IBA
  • regulation of neutrophil degranulation (GO:0043313) ISS
  • positive regulation of B cell differentiation (GO:0045579) IMP
  • positive regulation of 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
  • B cell receptor signaling pathway (GO:0050853) ISS
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 [102,242] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [180] ...
TANK binding kinase 1
(IKK family)
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
TBK1 belongs to the IKK-kinase family of enzymes. It is a ubiquitously expressed serine/threonine protein kinase, and constitutes a key regulatory node for several signaling pathways involved in the innate immune response that lead to induction of type I interferons. Several classes of innate sensors including the TLRs and retinoic acid-inducible gene 1 (RIG-I)-like helicases engage TBK1-IRF3 signaling pathways to regulate transcription of type I IFNs. In neuroinflammation TBK1 is involved in TLR-dependent [140] ...
tec protein tyrosine kinase
(Tec family)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell receptor signaling pathway (GO:0050853) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [32] ...
TXK tyrosine kinase
(Tec family)
  • T cell receptor signaling pathway (GO:0050852) ISS
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [32] ...
tyrosine kinase 2
(Janus kinase (JakA) family)
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
YES proto-oncogene 1, Src family tyrosine kinase
(Src family)
  • T cell costimulation (GO:0031295) TAS
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system.
zeta chain of T-cell receptor associated protein kinase 70
(Syk family)
  • 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 receptor signaling pathway (GO:0050852) TAS
ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [14] ...
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • positive regulation of natural killer cell differentiation (GO:0032825) IDA
  • erythrocyte homeostasis (GO:0034101) IEA
  • negative regulation of lymphocyte activation (GO:0051250) IEA
  • neutrophil clearance (GO:0097350) IEA
All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [109] ...
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • B cell homeostasis (GO:0001782) IEA
  • positive regulation of germinal center formation (GO:0002636) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • T cell costimulation (GO:0031295) IEA
  • B cell costimulation (GO:0031296) 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 ...
B cell maturation antigen
(Tumour necrosis factor (TNF) receptor family)
  • lymphocyte homeostasis (GO:0002260) IEA
B-cell maturation antigen (BCMA) is a cell surface receptor for B-cell activating factor (BAFF). It interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways. BCMA is highly plasma cell-selective for malignant plasma cells from multiple myeloma (MM) patients, and is being investigated as a target for for T-cell redirecting therapies to tackle relapsed/refractory MM. Novel anti-BCMA pharmacological agents in early stage development for MM include monoclonal antibodies and CAR-T cells [115,235,329] ...
CD27
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell differentiation (GO:0045579) NAS
  • positive regulation of T cell differentiation (GO:0045582) IEA
A co-stimulatory immune checkpoint molecule. Endogenous ligand is CD70. Interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1).
CD40
(Tumour necrosis factor (TNF) receptor family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of immune response (GO:0050776) TAS
  • regulation of immunoglobulin secretion (GO:0051023) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
CD40
(Tumour necrosis factor (TNF) receptor family)
  • immune response-regulating cell surface receptor signaling pathway (GO:0002768) IEA
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • regulation of immune response (GO:0050776) TAS
  • regulation of immunoglobulin secretion (GO:0051023) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of B cell proliferation (GO:0030889) ISS
  • negative regulation of T cell proliferation (GO:0042130) ISS
  • T cell receptor signaling pathway (GO:0050852) ISS
Expressed predominantly in the thymus, spleen and white blood cells. May play a role in T helper cell activation, inflammation and immune regulation. Signals via the TRADD adaptor protein to the NF-κB and MAPK8/JNK pathways.
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • positive regulation of defense response to virus by host (GO:0002230) IMP
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • RIG-I signaling pathway (GO:0039529) IMP
RIG-I is an intracellular sensor that responds to viral nucleic acids and activates downstream signaling, resulting in the induction of the type I interferon response [189] ...
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of MDA-5 signaling pathway (GO:0039534) IMP
  • negative regulation of RIG-I signaling pathway (GO:0039536) IDA
  • regulation of innate immune response (GO:0045088) IDA
  • negative regulation of innate immune response (GO:0045824) IDA
  • positive regulation of MDA-5 signaling pathway (GO:1900245) ISS
  • positive regulation of RIG-I signaling pathway (GO:1900246) ISS
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA.
Fas
(Tumour necrosis factor (TNF) receptor family)
  • activation-induced cell death of T cells (GO:0006924) IEA
  • regulation of lymphocyte differentiation (GO:0045619) IEA
  • regulation of myeloid cell differentiation (GO:0045637) IEA
  • negative regulation of B cell activation (GO:0050869) IEA
Fas receptor (CD95) is a cell surface protein that belongs to the tumor necrosis factor receptor family, that along with its ligand CD95L, generates a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. This system is also important in the immune elimination of virus-infected cells, cancer cells and autoreactive T cells. Mouse strains with mutations in Fas or CD95L develop lymphoproliferative conditions, indicating the importance of these proteins to immune cell homeostasis [279] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • leukocyte homeostasis (GO:0001776) ISS
FLT3 is the receptor for the cytokine Flt3 ligand (FLT3LG). Flt3 ligand is a growth factor akin to stem cell factor and colony stimulating factor 1, and is essential for hematopoietic progenitor cell development and expansion of both myeloid and lymphoid lineages. It is one of the growth factor receptors targeted by the chemotherapeutic tyrosine kinase inhibitor sorafenib.
Results from mouse experiments suggest that Flt3 ligand is effective in treating sepsis, by potentiating innate immune functions of dendritic cells and neutrophils and improving T cell function [228] ...
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)
  • regulation of myeloid cell differentiation (GO:0045637) IEA
herpes virus entry mediator
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IEA
  • 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)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IEA
  • 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)
  • regulation of immune response (GO:0050776) TAS
  • 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 [110] ...
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
(Integrins)
  • regulation of immune response (GO:0050776) 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)
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • regulation of immune response (GO:0050776) 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 [152] ...
interferon α/β receptor 1
(Interferon receptor family)
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
A subunit of the functional receptor for various interferons (NOT interferon γ).
Interferon α/β receptor 2
(Interferon receptor family)
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
A subunit of the functional receptor for various interferons (NOT interferon γ).
Interferon γ receptor 1
(Interferon receptor family)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
A subunit of the functional receptor for interferon γ.
Interferon γ receptor 2
(Interferon receptor family)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
A subunit of the functional receptor for interferon γ.
interferon induced with helicase C domain 1
(RIG-I-like receptor family)
  • cytoplasmic pattern recognition receptor signaling pathway in response to virus (GO:0039528) TAS
  • MDA-5 signaling pathway (GO:0039530) IDA
MDA5 is an intracellualar RNA sensor. It recognizes longer double-stranded RNA sequences than RIG-1. In autoimmunity, MDA5 has been specifically linked with type I diabetes and anti-MDA5 autoantibodies can be detected in patients with certain connective tissue autoimmune conditions [4,119,196] ...
Interferon-λ receptor subunit 1
(IL-10 receptor family)
  • regulation of defense response to virus by host (GO:0050691) IDA
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of defense response to virus by host (GO:0002230) IDA
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • 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 type immune response (GO:2000318) 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 13 receptor, α2
(IL-2 receptor family)
  • negative regulation of immunoglobulin production (GO:0002638) IEA
  • negative regulation of mast cell degranulation (GO:0043305) IEA
Interleukin 13 receptor, α2 acts as a high affinity decoy receptor for interleukin 13 that sequesters the ligand away from IL13Rα1 and is involved in down-regulating IL-13 responses in vivo. IL13ra2 null mice exhibit enhanced IL-13 responses [309] ...
Interleukin 17 receptor A
(IL-17 receptor family)
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) 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 B
(IL-17 receptor family)
  • positive regulation of inflammatory response (GO:0050729) IEA
IL17RB is a subunit of the heterodimeric interleukin-25 receptor.
interleukin 17 receptor C
(IL-17 receptor family)
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of inflammatory response (GO:0050729) 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 [95] ...
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • regulation of inflammatory response (GO:0050727) 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)
  • regulation of inflammatory response (GO:0050727) IEA
  • positive regulation of neutrophil extravasation (GO:2000391) IEA
This is one of the subunits of the functional IL-1 receptor type I heterodimer.
Interleukin 1 receptor, type II
(Immunoglobulin-like family of IL-1 receptors)
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IEA
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • negative regulation of type IV hypersensitivity (GO:0001808) IEA
  • immune response-inhibiting signal transduction (GO:0002765) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24.
Interleukin-22 receptor α2
(IL-10 receptor family)
  • negative regulation of inflammatory response (GO:0050728) IEA
IL22RA2 (a.k.a. IL-22 binding protein) appears to act as a high affinity, soluble monomeric decoy receptor for IL-22 capable of neutralizeing the potent antimicrobial activity of IL-22 [75,90] ...
Interleukin 23 receptor
(IL-12 receptor family)
  • positive regulation of T cell mediated cytotoxicity (GO:0001916) ISS
  • positive regulation of defense response to virus by host (GO:0002230) IDA
  • positive regulation of T-helper 1 type immune response (GO:0002827) IDA
  • positive regulation of natural killer cell proliferation (GO:0032819) IC
  • 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 osteoclast differentiation (GO:0045672) IC
  • positive regulation of NK T cell activation (GO:0051135) IC
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
  • 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 T-helper 1 type immune response (GO:0002827) IEA
  • negative regulation of type 2 immune response (GO:0002829) IEA
  • regulation of isotype switching to IgG isotypes (GO:0048302) IEA
This is the ligand binding subunit of the IL-27 receptor heterodimer, a complex with IL6ST (signal transducing subunit).
Interleukin-2 receptor subunit α
(IL-2 receptor family)
  • regulation of T cell tolerance induction (GO:0002664) IMP
  • activation-induced cell death of T cells (GO:0006924) IEA
  • 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
  • negative regulation of defense response to virus (GO:0050687) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
  • negative regulation of immune response (GO:0050777) 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-31 receptor, α subunit
(IL-6 receptor family)
  • negative regulation of macrophage activation (GO:0043031) NAS
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • positive regulation of immunoglobulin production (GO:0002639) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • positive regulation of mast cell degranulation (GO:0043306) 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 [114] ...
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • positive regulation of leukocyte chemotaxis (GO:0002690) TAS
IL6R polymorphisms are associated with asthma risk [91] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • positive regulation of acute inflammatory response (GO:0002675) IC
  • positive regulation of adaptive immune response (GO:0002821) IC
  • 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)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) IEA
  • 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)
  • erythrocyte differentiation (GO:0030218) ISS
  • Fc receptor signaling pathway (GO:0038093) 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 [105] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of lymphocyte activation (GO:0051250) IEA
  • neutrophil clearance (GO:0097350) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [31,298] ...
NLRC3
(NOD-like receptor family)
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) IDA
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) ISS
NLRC3 is an intracellular pattern recognition receptor of the innate immune system. It has been shown to directly interact with and inhibit the type I interferon response of the intracellular DNA sensor STING to cytosolic DNA, cyclic di-GMP (c-di-GMP), and DNA viruses [188,325] ...
NLRC4
(NOD-like receptor family)
  • activation of innate immune response (GO:0002218) ISS
As part of the innate inflammatory response to invading mobile bacteria, NLRC4 (Ipaf) in macrophages induces a pro-inflammatory response upon detection of cytosolic bacterial flagellin. In contrast, extracellular bacterial flagellin is detected by TLR5 [195] ...
NLRC5
(NOD-like receptor family)
  • positive regulation of interferon-gamma-mediated signaling pathway (GO:0060335) IDA
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IDA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IDA
NLRC5 is an intracellular pattern recognition receptor mediating an innate immune response to viral infection [210] ...
NLRP10
(NOD-like receptor family)
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
  • helper T cell enhancement of adaptive immune response (GO:0035397) ISS
  • positive regulation of T-helper 17 type immune response (GO:2000318) ISS
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [126] ...
NLRP3
(NOD-like receptor family)
  • negative regulation of acute inflammatory response (GO:0002674) IMP
  • positive regulation of type 2 immune response (GO:0002830) ISS
  • positive regulation of T-helper 2 cell differentiation (GO:0045630) ISS
  • negative regulation of inflammatory response (GO:0050728) IMP
  • positive regulation of T-helper 17 cell differentiation (GO:2000321) IEA
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) 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. 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 [19] ...
NLRP6
(NOD-like receptor family)
  • negative regulation of inflammatory response to antigenic stimulus (GO:0002862) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IEA
  • regulation of inflammatory response (GO:0050727) ISS
NLRP6 is an intracellular pattern recognition receptor (PRR). It is a member of the NACHT, LRR and PYD domains-containing protein (NALP) subfamily of PRRs. The presence of NALPs in inflammasomes underlies their involvement in regulating proinflammatory caspases (esp. caspase 1) ...
NLRX1
(NOD-like receptor family)
  • negative regulation of RIG-I signaling pathway (GO:0039536) IEA
  • negative regulation of innate immune response (GO:0045824) IEA
  • negative regulation of inflammatory response (GO:0050728) IEA
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections.
nucleotide binding oligomerization domain containing 1
(NOD-like receptor family)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • positive regulation of dendritic cell cytokine production (GO:0002732) IEA
  • positive regulation of type 2 immune response (GO:0002830) IMP
  • activation of MAPK activity involved in innate immune response (GO:0035419) ISS
  • positive regulation of gamma-delta T cell activation (GO:0046645) ISS
  • regulation of inflammatory response (GO:0050727) IC
  • positive regulation of B cell activation (GO:0050871) IDA
  • nucleotide-binding oligomerization domain containing signaling pathway (GO:0070423) TAS
  • nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IDA
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP).
Oncostatin M-specific receptor, β subunit
(IL-6 receptor family)
  • positive regulation of acute inflammatory response (GO:0002675) IC
Oncostatin M-specific receptor, β subunit (OSMR) is a component of two functional heterodimeric receptor complexes:
1. OSMR+ interleukin-6 receptor, β subunit (IL6ST) forms the receptor for oncostatin M
2. OSMR+ interleukin-31 receptor, α subunit forms the recept ...
OX40
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of B cell proliferation (GO:0030890) ISS
  • positive regulation of immunoglobulin secretion (GO:0051024) ISS
The OX40/OX40L pair is involved in late T-cell costimulatory signaling and both are transiently expressed following antigen recognition, and blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [303] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of fever generation by positive regulation of prostaglandin secretion (GO:0071812) ISS
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)
  • negative regulation of T cell mediated cytotoxicity (GO:0001915) ISS
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • positive regulation of T cell proliferation (GO:0042102) ISS
  • T cell receptor signaling pathway (GO:0050852) IDA
  • B cell receptor signaling pathway (GO:0050853) ISS
  • positive regulation of antigen receptor-mediated signaling pathway (GO:0050857) ISS
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 [72] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • B cell homeostasis (GO:0001782) IBA
  • negative regulation of B cell proliferation (GO:0030889) IBA
Lymphocyte-specific TNF superfamily receptor expressed on B cells. Endogenous ligands include APRIL, BAFF and CAML. Defects in the function of TACI can lead to immune system diseases (e.g. immunodeficiency).
TEK receptor tyrosine kinase
(Type XII RTKs: TIE family of angiopoietin receptors)
  • negative regulation of inflammatory response (GO:0050728) 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 [150] ...
TLR1
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 1 signaling pathway (GO:0034130) IEA
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [290] ...
TLR10
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 10 signaling pathway (GO:0034166) TAS
  • positive regulation of inflammatory response (GO:0050729) IEA
To date, ligands and biological functions of human TLR10 remain unclear. However, evidence suggests it plays a modulatory role with predominantly inhibitory (anti-inflammatory) effects [221] ...
TLR2
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) TAS
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • signaling pattern recognition receptor activity (GO:0008329) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 2 signaling pathway (GO:0034134) IEA
  • toll-like receptor TLR1:TLR2 signaling pathway (GO:0038123) TAS
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [206] ...
TLR3
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
  • positive regulation of inflammatory response (GO:0050729) IC
TLR3 is an endosomal anti-viral receptor [290] ...
TLR4
(Toll-like receptor family)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • positive regulation of B cell proliferation (GO:0030890) IEA
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 4 signaling pathway (GO:0034142) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • negative regulation of osteoclast differentiation (GO:0045671) NAS
  • positive regulation of inflammatory response (GO:0050729) IC
  • positive regulation of macrophage cytokine production (GO:0060907) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070430) IEA
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070434) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [34,237] ...
TLR5
(Toll-like receptor family)
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 5 signaling pathway (GO:0034146) TAS
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [195] ...
TLR6
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) IBA
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • toll-like receptor 6 signaling pathway (GO:0034150) IEA
  • toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124) TAS
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides from bacterial cell membranes, and effect an immune response [89] ...
TLR7
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 7 signaling pathway (GO:0034154) IBA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
TLR7 is an endosomal receptor detecting ssRNA [290] ...
TLR8
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • toll-like receptor 8 signaling pathway (GO:0034158) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • positive regulation of innate immune response (GO:0045089) IDA
TLR8 is an endosomal receptor detecting ssRNA [290] ...
TLR9
(Toll-like receptor family)
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) IEA
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) IDA
  • positive regulation of toll-like receptor signaling pathway (GO:0034123) IDA
  • toll-like receptor 9 signaling pathway (GO:0034162) TAS
  • positive regulation of inflammatory response (GO:0050729) IC
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [290] ...
tumor necrosis factor receptor 1
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of inflammatory response (GO:0050728) IMP
  • positive regulation of inflammatory response (GO:0050729) ISS
We have included TNFR1 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [107,211] ...
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • negative regulation of inflammatory response (GO:0050728) IEA
We have included TNFR2 in GtoImmuPdb based on it being a receptor for lymphotoxin-α, a cytotoxic protein performing a variety of important roles in immune system development and regulation [107,211] ...
TYRO3 protein tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of toll-like receptor signaling pathway (GO:0034122) ISS
  • negative regulation of innate immune response (GO:0045824) ISS
  • negative regulation of inflammatory response (GO:0050728) ISS
  • negative regulation of lymphocyte activation (GO:0051250) IEA
TYRO3 is a negative regulator of type 2 immunity [53] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) ISS
  • positive regulation of T-helper 1 type immune response (GO:0002827) ISS
NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [41,264,266] ...
Other Protein Targets
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
absent in melanoma 2
(Absent in melanoma (AIM)-like receptors (ALRs))
  • activation of innate immune response (GO:0002218) IDA
  • positive regulation of defense response to virus by host (GO:0002230) ISS
AIM2 primarily senses cytosolic DNA and initiates formation of an inflammasome to drive IL-1β cleavage and secretion.
advanced glycosylation end-product specific receptor
(Immunoglobulins)
  • regulation of T cell mediated cytotoxicity (GO:0001914) IDA
  • positive regulation of activated T cell proliferation (GO:0042104) IMP
  • negative regulation of connective tissue replacement involved in inflammatory response wound healing (GO:1904597) IEA
  • regulation of CD4-positive, alpha-beta T cell activation (GO:2000514) IDA
  • positive regulation of dendritic cell differentiation (GO:2001200) IMP
RAGE is a single chain, membrane bound immunoglobulin type protein [209,254,314] ...
B7-H3 (CD276)
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of immune response (GO:0050776) NAS
B7-H3 is a costimulatory molecule for T cell activation and IFN-γ production [56,81] ...
B7-H3 (CD276)
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IDA
  • regulation of immune response (GO:0050776) NAS
B7-H3 is a costimulatory molecule for T cell activation and IFN-γ production [56,81] ...
baculoviral IAP repeat containing 2
(Inhibitors of apoptosis (IAP) protein family)
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • regulation of innate immune response (GO:0045088) TAS
  • regulation of inflammatory response (GO:0050727) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [162] ...
baculoviral IAP repeat containing 3
(Inhibitors of apoptosis (IAP) protein family)
  • regulation of toll-like receptor signaling pathway (GO:0034121) TAS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
  • regulation of innate immune response (GO:0045088) TAS
  • regulation of inflammatory response (GO:0050727) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Cellular inhibitor of apoptosis proteins (cIAPs) suppress apoptosis thereby promoting cell survival, and participate in the immune response (e.g. negative regulation of the necrosome, inflammasome and ripoptosome. In asthma, cIAPs extend the survival of neutrophils, macrophages and eosinophils, prolonging the inflammation. The minor alleles of single nucleotide polymorphisms in BIRC3 are shown to correlate with reduced numbers of circulating eosinophils and neutrophils, suggesting a protective effect against the development of asthma[249] ...
BCL2, apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • B cell homeostasis (GO:0001782) IEA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • T cell homeostasis (GO:0043029) IEA
  • B cell receptor signaling pathway (GO:0050853) IMP
The role of Bcl-2 family members in immunity and disease is reviewed in [83] ...
butyrophilin subfamily 3 member A1
(Butyrophilin and butyrophilin-like proteins)
  • T cell receptor signaling pathway (GO:0050852) IDA
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [200] ...
CD159a
(CD molecules)
  • regulation of immune response (GO:0050776) TAS
NKG2A (KLRC1; CD159a) acts as an inhibitory checkpoint receptor for HLA-E. NKG2A forms functional heterodimers with CD94 (KLRD1) to form a human leukocyte antigen E (HLA-E) recognition complex on a subset of natural killer (NK) cells and cytotoxic T cells. NKG2A/CD94/HLA-E binding suppresses immune vigilance, and overexpression of HLA-E is used by cancer cells to evade immune recognition and destruction [80,169,186,262] ...
CD19
(CD molecules)
  • regulation of complement activation (GO:0030449) TAS
  • regulation of immune response (GO:0050776) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
CD19 is a B cell antigen used as a biomarker for normal and neoplastic B cells, and follicular dendritic cells. Anti-CD19 monoclonal antibodies are being investigated for potential clinical utility in oncology, transplantation and autimmune diseases (e.g. inebilizumab ...
CD2
(CD molecules)
  • positive regulation of myeloid dendritic cell activation (GO:0030887) NAS
  • regulation of T cell differentiation (GO:0045580) NAS
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [315] ...
CD209 molecule
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • 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)
  • positive regulation of inflammatory response to antigenic stimulus (GO:0002863) IEA
  • 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
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • T cell receptor signaling pathway (GO:0050852) 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] ...
CD28
(CD molecules)
  • positive regulation of inflammatory response to antigenic stimulus (GO:0002863) IEA
  • 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
  • positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
  • T cell receptor signaling pathway (GO:0050852) 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 B cell proliferation (GO:0030889) IMP
  • negative regulation of mast cell activation involved in immune response (GO:0033007) IDA
  • negative regulation of MyD88-dependent toll-like receptor signaling pathway (GO:0034125) IMP
  • negative regulation of mast cell degranulation (GO:0043305) IDA
  • regulation of immune response (GO:0050776) TAS
  • regulation of T cell receptor signaling pathway (GO:0050856) IDA
  • negative regulation of B cell receptor signaling pathway (GO:0050859) IDA
  • negative regulation of NK T cell activation (GO:0051134) IDA
  • negative regulation of neutrophil activation (GO:1902564) IDA
  • negative regulation of eosinophil activation (GO:1902567) IDA
  • negative regulation of eosinophil migration (GO:2000417) IDA
CD300a is a member of the CD300 family of leucocyte surface receptors [38] ...
CD33
(CD molecules)
  • regulation of immune response (GO:0050776) TAS
CD33 (SIGLEC-3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [99] ...
CD33
(CD molecules)
  • regulation of immune response (GO:0050776) TAS
CD33 (SIGLEC-3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [99] ...
CD38
(CD molecules)
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • B cell receptor signaling pathway (GO:0050853) IMP
CD38 is a type II transmembrane glycoprotein, widely expressed on immune cells and involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [108] ...
CD3e
(CD molecules)
  • positive regulation of T cell anergy (GO:0002669) IEA
  • 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
  • regulation of immune response (GO:0050776) TAS
  • T cell receptor signaling pathway (GO:0050852) TAS
CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [76,267] ...
CD47
(CD molecules)
  • positive regulation of inflammatory response (GO:0050729) IEA
  • positive regulation of T cell activation (GO:0050870) IDA
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 [177] ...
CD6
(CD molecules)
  • positive regulation of T cell proliferation (GO:0042102) IMP
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IDA
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 [205] ...
CD74
(CD molecules)
  • positive regulation of dendritic cell antigen processing and presentation (GO:0002606) IEA
  • positive regulation of type 2 immune response (GO:0002830) IEA
  • negative regulation of mature B cell apoptotic process (GO:0002906) IEA
  • positive regulation of B cell proliferation (GO:0030890) IMP
  • regulation of macrophage activation (GO:0043030) NAS
  • negative regulation of T cell differentiation (GO:0045581) IEA
  • positive regulation of T cell differentiation (GO:0045582) IEA
  • positive regulation of monocyte differentiation (GO:0045657) IDA
  • positive regulation of macrophage cytokine production (GO:0060907) ISS
  • positive regulation of neutrophil chemotaxis (GO:0090023) 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 [62] ...
CD79B
(CD molecules)
  • B cell receptor signaling pathway (GO:0050853) IBA
CD79B is a component of the multimeric B cell antigen receptor (along with CD79A and a membrane-bound antibody that acts as the antigen recognition moiety). The CD79A/B component is responsible for signal transduction. The B cell antigen receptor complex is reported to be involved in the pathogenesis of various B cell-derived lymphoid cancers [203,257] ...
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)
  • negative regulation of T cell anergy (GO:0002668) IEA
  • T cell costimulation (GO:0031295) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • 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)
  • negative regulation of T cell anergy (GO:0002668) IEA
  • T cell costimulation (GO:0031295) TAS
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • 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 ...
CREB binding protein
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
CS1 (CD319)
(CD molecules)
  • regulation of immune response (GO:0050776) TAS
CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions.

CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [149] ...
C-type lectin domain family 4 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
C-type lectin domain family 4 member E
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc-gamma receptor signaling pathway (GO:0038094) IEA
Mincle is an FcRγ-associated membrane receptor involved in initiating the innate immune response upon recognition of endogenous and exogenous ligands including Sin3A-associated protein (SAP130), α-mannan on fungal cell walls and mycobacterial cord factor (trehalose-6,6′-dimycolate (TDM)) [45] ...
C-type lectin domain family 6 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
Dectin-2 is involved in initiating the innate immune response upon recognition of high mannose structures on fungal cell walls. It associates with the ITAM-containing FcRβ adaptor and signals through the Syk, PKCδ, and CARD9-Bcl10-MALT1 pathways to promote cytokine production in response ...
C-type lectin domain family 7 member A
(C-type lectin-like receptors (CLRs))
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • signaling pattern recognition receptor activity (GO:0008329) IDA
Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [44] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • 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
  • negative regulation of immune response (GO:0050777) IEA
  • B cell receptor signaling pathway (GO:0050853) IMP
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 [193] ...
cytotoxic T-lymphocyte-associated protein 4 (CD152)
(CD molecules)
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • 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
  • negative regulation of immune response (GO:0050777) IEA
  • B cell receptor signaling pathway (GO:0050853) IMP
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 [193] ...
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
Fc fragment of IgE receptor Ia
(Fc epsilon receptors)
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • IgE receptor activity (GO:0019767) IEA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IEA
The product of the FCεR1A gene is a single-pass type I membrane protein that is a high-affinity receptor for immunoglobulin E (IgE). It is the ligand binding subunit of the tetrameric FCεRI, exhibiting a Kd of ~0.1nM.
Fc fragment of IgE receptor Ig
(Fc epsilon receptors)
  • positive regulation of type IIa hypersensitivity (GO:0001798) IEA
  • positive regulation of type III hypersensitivity (GO:0001805) IEA
  • positive regulation of type I hypersensitivity (GO:0001812) IEA
  • stimulatory C-type lectin receptor signaling pathway (GO:0002223) TAS
  • Fc receptor mediated stimulatory signaling pathway (GO:0002431) IBA
  • IgE receptor activity (GO:0019767) IBA
  • positive regulation of mast cell cytokine production (GO:0032765) IEA
  • negative regulation of mast cell apoptotic process (GO:0033026) IEA
  • Fc-gamma receptor signaling pathway (GO:0038094) IBA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • positive regulation of mast cell degranulation (GO:0043306) IEA
Fc fragment of IgE receptor II
(Fc epsilon receptors)
  • positive regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002925) IEA
FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [146,319] ...
heat shock protein 90 alpha family class B member 1
(Heat shock proteins)
  • Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) IMP
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) IMP
heat shock protein 90 beta family member 1
(Heat shock proteins)
  • toll-like receptor signaling pathway (GO:0002224) TAS
HSP90B1 is an endoplasmic reticulum chaperone required for proper folding and cell surface export of newly synthesized Toll-like receptor and integrin (CD11a, CD18 and CD49d) proteins. In its absence TLR responses are ablated, and there is no innate response to microbial stimuli [239] ...
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 [124] ...
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 [124] ...
immunoglobulin heavy constant epsilon
(Immunoglobulins)
  • complement activation, classical pathway (GO:0006958) IBA
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
  • B cell receptor signaling pathway (GO:0050853) IBA
  • positive regulation of B cell activation (GO:0050871) IBA
IgE is being investigated as a molecular target in allergic inflammatory conditions such as asthma, allergic rhinitis and chronic spontaneous urticaria. One anti-IgE monoclonal, omalizumab, has already been approved for use in patients with asthma or chronic spontaneous urticaria. Omalizumab binds t ...
interferon gamma inducible protein 16
(Absent in melanoma (AIM)-like receptors (ALRs))
  • activation of innate immune response (GO:0002218) IDA
  • negative regulation of innate immune response (GO:0045824) IDA
IFI16 is a sensor for cytosolic DNA which induces type I interferon production via activation of the IRF3/NFκB pathway.
LAG3 (CD223)
(CD molecules)
  • positive regulation of natural killer cell mediated cytotoxicity (GO:0045954) IEA
  • 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 [9] ...
LAG3 (CD223)
(CD molecules)
  • positive regulation of natural killer cell mediated cytotoxicity (GO:0045954) IEA
  • 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 [9] ...
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 [65] ...
lymphocyte antigen 96
(Lymphocyte antigens)
  • lipopolysaccharide receptor activity (GO:0001875) IDA
  • toll-like receptor signaling pathway (GO:0002224) TAS
  • MyD88-dependent toll-like receptor signaling pathway (GO:0002755) TAS
  • MyD88-independent toll-like receptor signaling pathway (GO:0002756) TAS
  • negative regulation of MyD88-independent toll-like receptor signaling pathway (GO:0034128) TAS
  • toll-like receptor 4 signaling pathway (GO:0034142) ISS
  • TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
LY96 (MD2) is a binding partner of Toll-like receptor 4 (TLR4), required to initiate an innate immune response to bacterial lipopolysaccharide (LPS). The signaling complex also contains CD14 co-receptor [153] ...
membrane spanning 4-domains A2
(Fc epsilon receptors)
  • Fc-epsilon receptor signaling pathway (GO:0038095) TAS
The protein product of the MS4A2 gene is the β subunit of the FCεRI. It has commonly known as FCER1B. The IgE-receptor (FCεRI), is a tetramer composed of an α, β, and 2 disulfide-linked γ chains expressed on the surface of mast cells and basophils that is crucial for mediating the allergic response. It has been suggested that cytoplasmic FCER1B that is not associated with FCεRI complexes may act as a negative regulator of the signalling pathway to degranulation by sequestering important signalling partners such as the Lyn tyrosine kinase [218] ...
myeloid cell nuclear differentiation antigen
(Absent in melanoma (AIM)-like receptors (ALRs))
  • negative regulation of B cell proliferation (GO:0030889) IMP
  • B cell receptor signaling pathway (GO:0050853) IMP
MNDA can be detected exclusively in nuclei of hematopoietic cells of the monocyte lineage. Expression is induced by interferon α [40] ...
programmed cell death 1 (CD279)
(CD molecules)
  • negative regulation of tolerance induction (GO:0002644) IEA
  • 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 [223] ...
programmed cell death 1 (CD279)
(CD molecules)
  • negative regulation of tolerance induction (GO:0002644) IEA
  • 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 [223] ...
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)
  • regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
  • negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002859) IEA
  • negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
  • negative regulation of natural killer cell activation (GO:0032815) IEA
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • toll-like receptor 7 signaling pathway (GO:0034154) IEA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • negative regulation of immunological synapse formation (GO:2000521) IEA
  • 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 [199] ...
TIM3 (CD366)
(CD molecules)
  • regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
  • negative regulation of T-helper 1 type immune response (GO:0002826) IEA
  • negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002859) IEA
  • negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
  • negative regulation of natural killer cell activation (GO:0032815) IEA
  • toll-like receptor 3 signaling pathway (GO:0034138) IEA
  • toll-like receptor 7 signaling pathway (GO:0034154) IEA
  • toll-like receptor 9 signaling pathway (GO:0034162) IEA
  • positive regulation of T cell proliferation (GO:0042102) IEA
  • negative regulation of T cell proliferation (GO:0042130) IEA
  • positive regulation of macrophage activation (GO:0043032) IEA
  • negative regulation of immunological synapse formation (GO:2000521) IEA
  • 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 [199] ...
transmembrane protein 173
(Other pattern recognition receptors)
  • activation of innate immune response (GO:0002218) IMP
  • positive regulation of defense response to virus by host (GO:0002230) IMP
STING functions as a major regulator of the innate immune response to viral and bacterial infections. Located in the endoplasmic reticulum, it acts as a pattern recognition receptor, activating type I interferon (IFN) responses upon direct binding to a variety of different cyclic-di-nucleotides (for example of pathogenic origin) [21,46,127-128] ...
X-linked inhibitor of apoptosis
(Inhibitors of apoptosis (IAP) protein family)
  • regulation of innate immune response (GO:0045088) TAS
  • regulation of inflammatory response (GO:0050727) TAS
  • regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
Mouse experiments suggest that XIAP regulates innate immune responses (to Listeria monocytogenes infection) by potentiating synergy between Toll-like receptors (TLRs) and NOD-like receptors (NLRs) through activation of JNK- and NF-κB-dependent signaling [29] ...