Targets Associated to Immuno Processes - Cytokine production & signalling

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Cytokine production & signalling
GPCRs
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
5-HT2B receptor
(5-Hydroxytryptamine receptors)
  • positive regulation of cytokine production (GO:0001819) IDA
  • positive regulation of cytokine secretion (GO:0050715) ISS
ACKR1
(Chemokine receptors)
  • regulation of chemokine production (GO:0032642) IBA
  • chemokine-mediated signaling pathway (GO:0070098) IEA
ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ACKR2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ACKR3
(Chemokine receptors)
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IMP
ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
ACKR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
ACKR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
A2B receptor
(Adenosine receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
A2B receptor is discussed in this immuno-oncology review [1] ...
C3a receptor
(Complement peptide receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
Complement C3a receptor 1 is the receptor for complement factor C3a, a component of the alternative complement cascade. It can have pro-inflammatory actions, but can also counteract the proinflammatory effects of C5a.
C5a1 receptor
(Complement peptide receptors)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) IEA
C5aR is typically associated with the compement cascade and innate immunity.
C5a2 receptor
(Complement peptide receptors)
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • negative regulation of interleukin-6 secretion (GO:1900165) IMP
  • regulation of interleukin-8 secretion (GO:2000482) 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.
CCR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) IDA
  • C-C chemokine receptor activity (GO:0016493) IDA
  • cytokine-mediated signaling pathway (GO:0019221) NAS
  • chemokine-mediated signaling pathway (GO:0070098) IDA
CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR10
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) IEA
CCR10 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • regulation of vascular endothelial growth factor production (GO:0010574) ISS
  • C-C chemokine receptor activity (GO:0016493) IEA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • positive regulation of interferon-gamma production (GO:0032729) ISS
  • positive regulation of interleukin-2 production (GO:0032743) ISS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) ISS
  • chemokine-mediated signaling pathway (GO:0070098) 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 [1] ...
CCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IEA
CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR4
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IEA
CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR5
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
CCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR5 is discussed in relation to immuno-oncology in [1] ...
CCR6
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IDA
CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR7
(Chemokine receptors)
  • C-C chemokine receptor activity (GO:0016493) ISS
  • regulation of interferon-gamma production (GO:0032649) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • C-C motif chemokine 19 receptor activity (GO:0038117) IDA
  • C-C motif chemokine 21 receptor activity (GO:0038121) IDA
  • regulation of interleukin-1 beta secretion (GO:0050706) ISS
  • cellular response to cytokine stimulus (GO:0071345) IDA
  • interleukin-12 secretion (GO:0072610) ISS
CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR8
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IEA
CCR8 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CCR9
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-C chemokine receptor activity (GO:0016493) IEA
CCR9 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Activation of CCR9 by CCL25 plays a key role in leukocyte recruitment to the gut and CCR9 antagonists are being pursued as therapeutic agents for inflammatory bowel disease [227] ...
CCRL2
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
CCRL2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. However, the nomenclature of CCLR2 for this receptor and its classification as a member of the chemokine receptor family is prov ...
chemerin receptor
(Chemerin receptor)
  • chemokine receptor activity (GO:0004950) TAS
  • negative regulation of interleukin-12 production (GO:0032695) ISS
The chemerin receptor is activated by the lipid-derived, anti-inflammatory autacoid ligand resolvin E1 ...
CXCR1
(Chemokine receptors)
  • interleukin-8 receptor activity (GO:0004918) IDA
  • chemokine receptor activity (GO:0004950) TAS
CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [1] ...
CXCR2
(Chemokine receptors)
  • interleukin-8 receptor activity (GO:0004918) IDA
  • C-X-C chemokine receptor activity (GO:0016494) IDA
CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [1] ...
CXCR3
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-X-C chemokine receptor activity (GO:0016494) IEA
  • chemokine (C-C motif) ligand 11 production (GO:0071954) IDA
CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes.
CXCR4
(Chemokine receptors)
  • C-X-C chemokine receptor activity (GO:0016494) NAS
  • cellular response to cytokine stimulus (GO:0071345) IDA
CXCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CXCR5
(Chemokine receptors)
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR5 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
CXCR6
(Chemokine receptors)
  • C-X-C chemokine receptor activity (GO:0016494) IEA
CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [216] ...
CX3CR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
  • C-X3-C chemokine receptor activity (GO:0016495) IEA
CX3CR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
EP4 receptor
(Prostanoid receptors)
  • negative regulation of cytokine secretion (GO:0050710) ISS
  • positive regulation of cytokine secretion (GO:0050715) ISS
The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [242] ...
FFA2 receptor
(Free fatty acid receptors)
  • positive regulation of cytokine production involved in immune response (GO:0002720) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
  • positive regulation of interleukin-8 secretion (GO:2000484) IMP
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 chemokine production (GO:0032722) ISS
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [29] ...
GPR35
(Class A Orphans)
  • C-X-C chemokine receptor activity (GO:0016494) IMP
  • chemokine-mediated signaling pathway (GO:0070098) IDA
GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17 [170] ...
PAF receptor
(Platelet-activating factor receptor)
  • cytokine production (GO:0001816) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) IEA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
PAF deficiency results in defective inflammatory response to infection in mice.
PAR2
(Proteinase-activated receptors)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IDA
  • negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804) IDA
  • chemokine (C-C motif) ligand 2 secretion (GO:0035926) IDA
  • interleukin-1 beta secretion (GO:0050702) IDA
  • interleukin-10 secretion (GO:0072608) IDA
  • interferon-gamma secretion (GO:0072643) ISS
  • chemokine secretion (GO:0090195) IDA
  • negative regulation of chemokine secretion (GO:0090198) IDA
  • positive regulation of interleukin-8 secretion (GO:2000484) IDA
  • positive regulation of interleukin-6 secretion (GO:2000778) 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) [73] ...
S1P3 receptor
(Lysophospholipid (S1P) receptors)
  • cytokine production (GO:0001816) IEA
  • regulation of interleukin-1 beta production (GO:0032651) IEA
In the immune system S1P receptors regulate immune cell trafficking and mitogenesis, are involved in immune-modulation, and suppression of innate immune T cell responses.
XCR1
(Chemokine receptors)
  • chemokine receptor activity (GO:0004950) TAS
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [120] ...
Nuclear Hormone Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
Farnesoid X receptor
(1H. Liver X receptor-like receptors)
  • negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804) IEA
  • negative regulation of interleukin-1 production (GO:0032692) IEA
  • negative regulation of interleukin-2 production (GO:0032703) IEA
  • negative regulation of interleukin-6 production (GO:0032715) IEA
  • negative regulation of monocyte chemotactic protein-1 production (GO:0071638) IEA
  • interleukin-17 secretion (GO:0072615) IDA
  • negative regulation of interferon-gamma secretion (GO:1902714) IDA
  • negative regulation of tumor necrosis factor secretion (GO:1904468) IDA
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) [189] ...
Liver X receptor-α
(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 [234] ...
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 [234] ...
Enzymes
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
ABL proto-oncogene 1, non-receptor tyrosine kinase
(Abl family)
  • positive regulation of interleukin-2 secretion (GO:1900042) IEA
  • positive regulation of interferon-gamma secretion (GO:1902715) IEA
Included in GtoImmuPdb based on its association with leukemia.
ADAM17
(M12: Astacin/Adamalysin)
  • positive regulation of chemokine production (GO:0032722) IMP
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The proteolytic activity of ADAM17 (a type I transmembrane metalloproteinase; a.k.a.TNF-alpha converting enzyme or TACE) is involved in the shedding of the extracellular domains of several transmembrane proteins e.g. cytokines (TNFα), growth factors, receptors (IL-6R and TNF-R for example) and adhesion molecules. Cleavage of substrates, including TNFα, IL-6R and L-selectin, produce pro-inflammatory effects stimulating both innate and acquired immune responses. ADAM17 activity is crucial during development (ADAM17 knockout is embryonic lethal), and it has been shown that the soluble IL-6R/IL-6 complex generates agonist-like signals in a process termed IL-6 trans-signaling. The generation and maintenance of several inflammatory and autoimmune diseases is driven by IL-6 trans-signaling [36] ...
ADAM8
(M12: Astacin/Adamalysin)
  • positive regulation of tumor necrosis factor (ligand) superfamily member 11 production (GO:2000309) 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) [168] ...
Arginase I
(Arginase)
  • cellular response to interleukin-4 (GO:0071353) IEA
The role of ARG1 in immuno-oncology is reviewed in [1] ...
Bruton tyrosine kinase
(Tec family)
  • negative regulation of cytokine production (GO:0001818) IEA
  • regulation of B cell cytokine production (GO:0002721) TAS
  • cellular response to interleukin-7 (GO:0098761) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [21] ...
Caspase 3
(C14: Caspase)
  • response to tumor necrosis factor (GO:0034612) TAS
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 [161] ...
Caspase 8
(C14: Caspase)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • response to tumor necrosis factor (GO:0034612) IMP
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 [136] ...
conserved helix-loop-helix ubiquitous kinase
(IKK family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IBA
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • positive regulation of interferon-alpha secretion (GO:1902741) IMP
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 [92] ...
COX-2
(Cyclooxygenase)
  • positive regulation of vascular endothelial growth factor production (GO:0010575) ISS
  • response to tumor necrosis factor (GO:0034612) IEA
  • positive regulation of transforming growth factor beta production (GO:0071636) ISS
  • positive regulation of fibroblast growth factor production (GO:0090271) ISS
  • positive regulation of platelet-derived growth factor production (GO:0090362) ISS
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 [1] ...
C-terminal Src kinase
(Csk family)
  • regulation of cytokine production (GO:0001817) IBA
  • negative regulation of interleukin-6 production (GO:0032715) IEA
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 [219] ...
DNA-dependent protein kinase catalytic subunit
(Other PIKK family kinases)
  • positive regulation of type I interferon production (GO:0032481) TAS
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 ...
elastase, neutrophil expressed
(S1: Chymotrypsin)
  • negative regulation of chemokine biosynthetic process (GO:0045079) IDA
  • negative regulation of interleukin-8 biosynthetic process (GO:0045415) IDA
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IDA
Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host e ...
eukaryotic translation initiation factor 2 alpha kinase 2
(Other PEK family kinases)
  • positive regulation of cytokine production (GO:0001819) ISS
  • positive regulation of chemokine production (GO:0032722) ISS
  • response to interferon-alpha (GO:0035455) IDA
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 [72] ...
FER tyrosine kinase
(Fer family)
  • cytokine-mediated signaling pathway (GO:0019221) IMP
  • cellular response to macrophage colony-stimulating factor stimulus (GO:0036006) IMP
  • Kit signaling pathway (GO:0038109) ISS
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
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)
  • positive regulation of cytokine secretion (GO:0050715) ISS
Fgr may be involved in neutrophil migration, potentially via binding to intergrins [17] ...
Haem oxygenase 1
(Haem oxygenase)
  • negative regulation of mast cell cytokine production (GO:0032764) IEA
  • positive regulation of chemokine biosynthetic process (GO:0045080) TAS
Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO).

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

HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [8] ...
HCK proto-oncogene, Src family tyrosine kinase
(Src family)
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [17] ...
IL2 inducible T-cell kinase
(Tec family)
  • cytokine production (GO:0001816) ISS
  • interferon-gamma production (GO:0032609) IEA
  • interleukin-4 production (GO:0032633) IEA
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [21] ...
indoleamine 2,3-dioxygenase 1
(1.13.11.- Dioxygenases)
  • cytokine production involved in inflammatory response (GO:0002534) IEA
  • negative regulation of interleukin-10 production (GO:0032693) IEA
  • positive regulation of interleukin-12 production (GO:0032735) IEA
Depletion of tryptophan (catalyzed by IDO1) promotes Treg cell differentiation, suppresses the immune response and decreases DC function, creating a tolerogenic environment. IDO1 inhibitors reverse this response. ID01 has emerged as a promising molecular target for the development of novel agents as cancer immunotherapeutics, and for the treatment of other diseases characterized by the reduction of local tryptophan levels. The applicability of ID01 inhibition has been shown preclinical models of many diseases, including arthritis, ischemia-reperfusion injury, endotoxin shock, human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, airway inflammation, and cancer [88,217] ...
Inducible NOS
(Nitric oxide synthases)
  • cellular response to interferon-gamma (GO:0071346) IEA
  • interleukin-6 secretion (GO:0072604) IDA
  • interleukin-8 secretion (GO:0072606) IDA
  • regulation of cytokine production involved in inflammatory response (GO:1900015) IDA
The role of iNOS in immuno-oncology is reviewed in [1] ...
inhibitor of nuclear factor kappa B kinase subunit beta
(IKK family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • cellular response to tumor necrosis factor (GO:0071356) IDA
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) [2,19,25,196] ...
inhibitor of nuclear factor kappa B kinase subunit epsilon
(IKK family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • response to type I interferon (GO:0034340) IEA
  • response to interferon-beta (GO:0035456) IMP
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 interleukin-6 biosynthetic process (GO:0045409) IEA
SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [156,202] ...
interleukin 1 receptor associated kinase 1
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • regulation of cytokine-mediated signaling pathway (GO:0001959) IMP
  • positive regulation of type I interferon production (GO:0032481) IMP
  • type I interferon signaling pathway (GO:0060337) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
One of the two proximal mediators of IL-1 signaling via the IL-1 receptor, plays a part in IL-1-induced upregulation of the transcription factor NF-κB, the other being IRAK2. Interacts with other proteins including TRAF6, Myd88, CHUK, IKK2 and TLR4.
interleukin 1 receptor associated kinase 2
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • regulation of cytokine-mediated signaling pathway (GO:0001959) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
interleukin 1 receptor associated kinase 3
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • negative regulation of cytokine-mediated signaling pathway (GO:0001960) IC
  • negative regulation of macrophage cytokine production (GO:0010936) ISS
  • cytokine-mediated signaling pathway (GO:0019221) ISS
  • negative regulation of interleukin-12 production (GO:0032695) IMP
  • negative regulation of interleukin-6 production (GO:0032715) IMP
  • negative regulation of tumor necrosis factor production (GO:0032720) IMP
  • interleukin-1-mediated signaling pathway (GO:0070498) IMP
  • response to interleukin-1 (GO:0070555) IMP
IRAK3 expression is restricted to monocytes and macrophages.
interleukin 1 receptor associated kinase 4
(Interleukin-1 receptor-associated kinase (IRAK) family)
  • cytokine production (GO:0001816) IEA
  • interleukin-1-mediated signaling pathway (GO:0070498) IBA
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 [142] ...
Janus kinase 1
(Janus kinase (JakA) family)
  • interleukin-2-mediated signaling pathway (GO:0038110) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • type I interferon signaling pathway (GO:0060337) 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)
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • positive regulation of interleukin-1 beta production (GO:0032731) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IDA
  • response to tumor necrosis factor (GO:0034612) IDA
  • interleukin-12-mediated signaling pathway (GO:0035722) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) TAS
  • response to interleukin-12 (GO:0070671) IDA
CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [203] ...
Janus kinase 3
(Janus kinase (JakA) family)
  • negative regulation of dendritic cell cytokine production (GO:0002731) ISS
  • negative regulation of interleukin-10 production (GO:0032693) ISS
  • negative regulation of interleukin-12 production (GO:0032695) ISS
  • interleukin-4-mediated signaling pathway (GO:0035771) IDA
  • response to interleukin-2 (GO:0070669) TAS
  • response to interleukin-4 (GO:0070670) IDA
  • response to interleukin-15 (GO:0070672) TAS
  • response to interleukin-9 (GO:0071104) TAS
Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [5] ...
LYN proto-oncogene, Src family tyrosine kinase
(Src family)
  • regulation of cytokine production (GO:0001817) ISS
  • cytokine secretion (GO:0050663) IEA
  • regulation of cytokine secretion (GO:0050707) IEA
LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [68,71,212] ...
mitogen-activated protein kinase 1
(ERK subfamily)
  • cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011) 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 [110,133] ...
mitogen-activated protein kinase kinase kinase 7
(TAK1 subfamily)
  • positive regulation of T cell cytokine production (GO:0002726) IMP
  • positive regulation of interleukin-2 production (GO:0032743) IMP
TAK1 (MAP3K7) mediates signaling downstream of multiple cytokine receptors and is functionally important in mitogen, immune, and inflammatory signaling pathways [51,184] ...
MMP12
(M10: Matrix metallopeptidase)
  • negative regulation of type I interferon-mediated signaling pathway (GO:0060339) IEA
  • positive regulation of type I interferon-mediated signaling pathway (GO:0060340) IEA
  • positive regulation of interferon-alpha secretion (GO:1902741) IEA
MMP12 is included in GtoImmuPdb based on its reported involvement in asthma and potential as a asthma therapeutic target.
otulin
(C101: OTULIN peptidase)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) IDA
Otulin is reported as a negative regulator of inflammation and autoimmunity [54] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • cytokine production (GO:0001816) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [1] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • cytokine production (GO:0001816) TAS
The potential for PI3kδ as ta arget in immuno-oncology is discussed in [1] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • cytokine production (GO:0001816) TAS
The role of PIK3CG in immuno-oncology is reviewed in [1] ...
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
(Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
  • cytokine production (GO:0001816) TAS
The role of PIK3CG in immuno-oncology is reviewed in [1] ...
phosphoinositide-3-kinase regulatory subunit 1
(Phosphatidylinositol kinases)
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
p85α is included in GtoImmuPdb as it is the regulatory subunit of several PI3Ks (e.g. PI3Kδ and PI3Kγ) with roles in leukocyte biology and therefore important for immunity [130] ...
PLCγ2
(Phosphoinositide-specific phospholipase C)
  • positive regulation of type I interferon production (GO:0032481) IEA
Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [75,183] ...
proteasome subunit beta 8
(T1: Proteasome)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • type I interferon signaling pathway (GO:0060337) TAS
PSMB8 is a component of the immunoproteasome [66] ...
protein kinase C alpha
(Delta subfamily)
  • response to interleukin-1 (GO:0070555) IMP
PKCα is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C delta
(Delta subfamily)
  • interleukin-10 production (GO:0032613) IEA
  • interleukin-12 production (GO:0032615) IEA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
PKCδ is included in GtoImmuPdb based on its GO immune process associations.
protein kinase C iota
(Iota subfamily)
  • response to interleukin-1 (GO:0070555) IEA
PKCι is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes.
protein kinase C theta
(Delta subfamily)
  • positive regulation of interleukin-17 production (GO:0032740) ISS
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) IEA
PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [11] ...
protein kinase C zeta
(Iota subfamily)
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • positive regulation of T-helper 2 cell cytokine production (GO:2000553) ISS
  • positive regulation of interleukin-5 secretion (GO:2000664) ISS
  • positive regulation of interleukin-13 secretion (GO:2000667) ISS
  • positive regulation of interleukin-10 secretion (GO:2001181) ISS
PKCζ is included in GtoImmuPdb based on its GO process associations.
protein tyrosine kinase 2 beta
(Fak family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IMP
  • chemokine-mediated signaling pathway (GO:0070098) 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 [39] ...
receptor interacting serine/threonine kinase 1
(Receptor interacting protein kinase (RIPK) family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) IDA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • response to tumor necrosis factor (GO:0034612) IMP
  • cellular response to tumor necrosis factor (GO:0071356) IDA
RIPK1 and RIPK3 are involved in necroptosis [176,195,221] ...
receptor interacting serine/threonine kinase 2
(Receptor interacting protein kinase (RIPK) family)
  • positive regulation of cytokine-mediated signaling pathway (GO:0001961) IEA
  • positive regulation of chemokine production (GO:0032722) IEA
  • positive regulation of interferon-alpha production (GO:0032727) NAS
  • positive regulation of interferon-beta production (GO:0032728) NAS
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • positive regulation of interleukin-12 production (GO:0032735) NAS
  • positive regulation of interleukin-2 production (GO:0032743) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • response to interleukin-1 (GO:0070555) IEA
  • response to interleukin-12 (GO:0070671) IEA
  • response to interleukin-18 (GO:0070673) IEA
RIPK2 is involved in innate immune responses, mediating pro-inflammatory signaling from the bacterial peptidoglycan-sensing NOD1/NOD2 subfamily of innate immune pattern recognition receptors (PRRs) and signalling downstream from the Toll-like receptor (TLR) family of PRRs. Further evidence suggesting an inflammatory role is the targeting of RIPK2 (along with RIPK1/3) by the IAP family E3 ubiquitin ligases (enzymes playing a critical role in innate immunity) [159] ...
receptor interacting serine/threonine kinase 3
(Receptor interacting protein kinase (RIPK) family)
  • regulation of interferon-gamma production (GO:0032649) ISS
RIPK1 and RIPK3 are involved in necroptosis [176,195,221] ...
sirtuin 1
(3.5.1.- Histone deacetylases (HDACs))
  • macrophage cytokine production (GO:0010934) ISS
  • leptin-mediated signaling pathway (GO:0033210) ISS
  • cellular response to tumor necrosis factor (GO:0071356) 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 [40] ...
sPLA2-1B
(Phospholipase A2)
  • interleukin-8 production (GO:0032637) 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 [117] ...
spleen associated tyrosine kinase
(Syk family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) IMP
  • positive regulation of type I interferon production (GO:0032481) IEA
  • positive regulation of interleukin-3 biosynthetic process (GO:0045401) IEA
  • positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process (GO:0045425) IEA
  • positive regulation of cytokine secretion (GO:0050715) IEA
SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [74,175] ...
SRC proto-oncogene, non-receptor tyrosine kinase
(Src family)
  • positive regulation of cytokine secretion (GO:0050715) IEA
  • response to interleukin-1 (GO:0070555) IMP
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 [128] ...
TANK binding kinase 1
(IKK family)
  • regulation of type I interferon production (GO:0032479) TAS
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of type I interferon production (GO:0032481) TAS
  • type I interferon production (GO:0032606) TAS
  • positive regulation of interferon-alpha production (GO:0032727) IDA
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IEA
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 [105] ...
TXK tyrosine kinase
(Tec family)
  • cytokine production (GO:0001816) ISS
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • 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 [21] ...
tyrosine kinase 2
(Janus kinase (JakA) family)
  • type I interferon signaling pathway (GO:0060337) TAS
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) TAS
Catalytic Receptors
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
4-1BB
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • negative regulation of interleukin-10 secretion (GO:2001180) IEA
  • negative regulation of interleukin-12 secretion (GO:2001183) IEA
Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity [67] ...
AXL receptor tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • positive regulation of cytokine-mediated signaling pathway (GO:0001961) IDA
  • negative regulation of interferon-gamma production (GO:0032689) IDA
  • negative regulation of tumor necrosis factor production (GO:0032720) IEA
  • cellular response to interferon-alpha (GO:0035457) IDA
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 [81] ...
BAFF receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) 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)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
A cell surface receptor for B-cell activating factor (BAFF). Interacts with various TRAF family adaptor proteins to modulate cell survival and proliferation, via NF-κB and MAPK8/JNK signal transduction pathways.
CD27
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
A co-stimulatory immune checkpoint molecule. Endogenous ligand is CD70. Interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1).
CD30
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IDA
  • positive regulation of TRAIL biosynthetic process (GO:0045556) IDA
Expressed by activated T and B cells. Interacts with TRAF2 and TRAF5 to elicit downstream signalling events (NF-κB activation). CD30 may protect against autoimmunity by limiting the proliferative potential of autoreactive CD8 effector T cells. CD30 is the target of the approved anti-lymphoma monoclonal antibody drug brentuximab vedotin ...
CD40
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • positive regulation of interleukin-12 production (GO:0032735) IEA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • response to interferon-gamma (GO:0034341) IEA
  • cellular response to erythropoietin (GO:0036018) IEA
  • cellular response to interleukin-1 (GO:0071347) IEA
A costimulatory protein found on antigen presenting cells, required for their activation. Endogenous ligand is CD154 (CD40L) on TH cells.
CIITA
(NOD-like receptor family)
  • response to interferon-gamma (GO:0034341) IDA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
CIITA is a transcriptional coactivator for the transcription factor RFX5 [188] ...
colony stimulating factor 1 receptor
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • macrophage colony-stimulating factor receptor activity (GO:0005011) IMP
  • cytokine-mediated signaling pathway (GO:0019221) IMP
  • cellular response to macrophage colony-stimulating factor stimulus (GO:0036006) IMP
  • macrophage colony-stimulating factor signaling pathway (GO:0038145) ISS
  • cellular response to cytokine stimulus (GO:0071345) ISS
  • positive regulation of chemokine secretion (GO:0090197) IMP
Activation of the CSF1R induces myeloid proliferation, and in the tumour microenvironment this promotes M1 to M2 polarization and accumulation of tumour-associated macrophages (TAMs). The CSF1R is therefore being investigated as an immuno-oncology drug target [1] ...
Cytokine receptor common β subunit
(IL-3 receptor family)
  • cytokine receptor activity (GO:0004896) IEA
  • cellular response to interleukin-3 (GO:0036016) IEA
  • interleukin-5-mediated signaling pathway (GO:0038043) IEA
  • interleukin-3-mediated signaling pathway (GO:0038156) IEA
This a signal transducing protein subunit shared by the functional receptor heterodimers for the cytokines IL-3, IL-5 and GM-CSF, with each receptor having a unique ligand binding alpha subunit.
death receptor 3
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
In the absence of any other exogenous signals, activation of DR3 causes proliferation of FoxP3+ regulatory T cells [190] ...
death receptor 6
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • cellular response to tumor necrosis factor (GO:0071356) IDA
  • negative regulation of interleukin-5 secretion (GO:2000663) ISS
  • negative regulation of interleukin-13 secretion (GO:2000666) ISS
  • negative regulation of interleukin-10 secretion (GO:2001180) 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.
decoy receptor 3
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The protein product of the TNFRSF6B gene, known as decoy receptor 3 (DcR3), is a soluble endogenous receptor for three TNF family peptide ligands, LIGHT, TL1A and Fas ligand. DcR3 competes for ligand binding with death receptors. DcR3 suppresses LIGHT and FAS ligand induced apoptosis and T cell activation, and increases monocyte adhesion to endothelial cells via NF-κB activation [238] ...
DExD/H-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725) IDA
  • positive regulation of interferon-alpha production (GO:0032727) IDA
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • regulation of type III interferon production (GO:0034344) TAS
  • 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 [138] ...
DExH-box helicase 58
(RIG-I-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) IDA
  • positive regulation of type I interferon production (GO:0032481) ISS
  • negative regulation of MDA-5 signaling pathway (GO:0039534) IMP
  • negative regulation of RIG-I signaling pathway (GO:0039536) IDA
  • positive regulation of MDA-5 signaling pathway (GO:1900245) ISS
  • positive regulation of RIG-I signaling pathway (GO:1900246) ISS
LGP2 binds RNA but does not participate in the signaling pathway that RIG-1 and MDA5 are part of, and is assumed to provide a negative feedback for IFNβ induction by sequestering pathogen-derived RNA.
Fas
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
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 [206] ...
fms related tyrosine kinase 3
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • cytokine receptor activity (GO:0004896) ISS
  • cytokine-mediated signaling pathway (GO:0019221) ISS
  • cellular response to cytokine stimulus (GO:0071345) 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 [167] ...
glucocorticoid-induced TNF receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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.
GM-CSF receptor, α subunit
(IL-3 receptor family)
  • cytokine receptor activity (GO:0004896) IEA
This is the ligand binding subunit of the functional GM-CSF receptor complex.
Granulocyte colony-stimulating factor receptor
(Prolactin receptor family)
  • cytokine receptor activity (GO:0004896) IEA
herpes virus entry mediator
(Tumour necrosis factor (TNF) receptor family)
  • positive regulation of cytokine secretion involved in immune response (GO:0002741) IEA
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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)
  • cellular response to cytokine stimulus (GO:0071345) 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 [82] ...
interferon α/β receptor 1
(Interferon receptor family)
  • type I interferon receptor activity (GO:0004905) IDA
  • interleukin-10 receptor activity (GO:0004920) IBA
  • positive regulation of interferon-beta production (GO:0032728) IEA
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • cellular response to interferon-alpha (GO:0035457) ISS
  • type I interferon biosynthetic process (GO:0045351) IEA
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IEA
  • type I interferon signaling pathway (GO:0060337) IDA
  • 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)
  • type I interferon receptor activity (GO:0004905) IDA
  • response to interferon-alpha (GO:0035455) IDA
  • response to interferon-beta (GO:0035456) IMP
  • type I interferon signaling pathway (GO:0060337) IDA
  • 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)
  • interferon-gamma receptor activity (GO:0004906) TAS
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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)
  • interferon-gamma receptor activity (GO:0004906) TAS
  • interleukin-10 receptor activity (GO:0004920) IBA
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
  • 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)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • positive regulation of interferon-alpha production (GO:0032727) IMP
  • positive regulation of interferon-beta production (GO:0032728) IDA
  • regulation of type III interferon production (GO:0034344) TAS
  • 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 [3,90,144] ...
Interferon-λ receptor subunit 1
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
  • response to type III interferon (GO:0034342) ISS
Interferon-λ receptor subunit 1 is the ligand binding component of the functional heterodimeric receptor for interferons λ1, λ2 and λ3
Interleukin 10 receptor, α subunit
(IL-10 receptor family)
  • interleukin-10 receptor activity (GO:0004920) IBA
Interleukin 10 receptor, α subunit is a component of the functional IL-10 receptor heterodimer.
Interleukin 10 receptor, β subunit
(IL-10 receptor family)
  • cytokine-mediated signaling pathway (GO:0019221) IEA
Interleukin 10 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 10 and 22 and for interferons λ1, λ2 and λ3.
Interleukin-11 receptor, α subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) IEA
This is the ligand-binding component of the functional receptor for interleukin 11.
Interleukin-12 receptor, β1 subunit
(IL-12 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • interleukin-12-mediated signaling pathway (GO:0035722) IEA
  • interleukin-23-mediated signaling pathway (GO:0038155) IEA
  • cellular response to interferon-gamma (GO:0071346) IDA
This protein is a subunit of both the IL-12 and IL-23 cytokine receptors.
Interleukin-12 receptor, β2 subunit
(IL-12 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
  • interferon-gamma production (GO:0032609) IEA
  • positive regulation of interferon-gamma production (GO:0032729) IDA
This protein is a subunit of the functional receptor heterodimer for the IL-12 cytokine.
Interleukin 13 receptor, α2
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
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 [231] ...
Interleukin-13 receptor subunit α1
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IEA
Interleukin-13 receptor subunit α1 is a component of the functional heterodimeric receptor for interleukin 13 and the (type II) IL-4 receptor.
Interleukin-15 receptor subunit α
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
This is the ligand binding subunit of the functional IL-15 receptor complex.
Interleukin 17 receptor A
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
  • positive regulation of interleukin-23 production (GO:0032747) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
  • positive regulation of interleukin-5 secretion (GO:2000664) IEA
  • positive regulation of interleukin-13 secretion (GO:2000667) 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)
  • cytokine receptor activity (GO:0004896) NAS
  • interleukin-17 receptor activity (GO:0030368) IBA
  • positive regulation of interleukin-5 secretion (GO:2000664) IEA
  • positive regulation of interleukin-13 secretion (GO:2000667) IEA
IL17RB is a subunit of the heterodimeric interleukin-25 receptor.
interleukin 17 receptor C
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IDA
  • positive regulation of cytokine production involved in inflammatory response (GO:1900017) IEA
  • positive regulation of interleukin-6 secretion (GO:2000778) IEA
This is a subunit of the heterodimeric interleukin-17 receptor.
Interleukin-17 receptor D
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
IL17RD acts as an inhibitor of proinflammatory cytokine signaling (by limiting NF-κB translocation to the nucleus) [69] ...
Interleukin 17 receptor E
(IL-17 receptor family)
  • interleukin-17 receptor activity (GO:0030368) IBA
This is a component of the heterodimeric interleukin-17C receptor.
Interleukin-18 1
(Immunoglobulin-like family of IL-1 receptors)
  • interleukin-1 receptor activity (GO:0004908) IEA
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • interleukin-18 receptor activity (GO:0042008) IEA
Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer.
Interleukin-1 receptor-like 1
(Immunoglobulin-like family of IL-1 receptors)
  • interleukin-33 receptor activity (GO:0002114) IEA
  • cytokine receptor activity (GO:0004896) TAS
  • interleukin-1 receptor activity (GO:0004908) IEA
  • negative regulation of interferon-gamma production (GO:0032689) IEA
  • positive regulation of interleukin-5 production (GO:0032754) IEA
  • positive regulation of chemokine secretion (GO:0090197) IEA
IL1RL1 (ST2) is the ligand binding subunit of the functional receptor for IL-33. It is mainly expressed on mast cells, eosinophils and other immune cells [70] ...
Interleukin-1 receptor-like 2
(Immunoglobulin-like family of IL-1 receptors)
  • interleukin-1 receptor activity (GO:0004908) TAS
  • interleukin-1, Type I, activating receptor activity (GO:0004909) IEA
  • positive regulation of interleukin-6 production (GO:0032755) 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)
  • interleukin-1 receptor activity (GO:0004908) IDA
  • interleukin-1, Type I, activating receptor activity (GO:0004909) TAS
  • interleukin-1-mediated signaling pathway (GO:0070498) IDA
  • response to interleukin-1 (GO:0070555) IDA
  • positive regulation of interleukin-1-mediated signaling pathway (GO:2000661) 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)
  • interleukin-1 receptor activity (GO:0004908) TAS
  • interleukin-1, Type II, blocking receptor activity (GO:0004910) IEA
  • negative regulation of interleukin-1 alpha secretion (GO:0050712) IEA
  • negative regulation of cytokine production involved in inflammatory response (GO:1900016) IEA
  • negative regulation of interleukin-1-mediated signaling pathway (GO:2000660) IEA
Interleukin 20 receptor, α subunit
(IL-10 receptor family)
  • cytokine receptor activity (GO:0004896) IBA
  • cytokine-mediated signaling pathway (GO:0019221) IBA
Interleukin 20 receptor, α subunit is a component of the functional receptor heterodimer for interleukin 20.
Interleukin 20 receptor, β subunit
(IL-10 receptor family)
  • interleukin-10 receptor activity (GO:0004920) IBA
  • negative regulation of interferon-gamma production (GO:0032689) IEA
  • negative regulation of interleukin-2 production (GO:0032703) IEA
  • positive regulation of interleukin-10 production (GO:0032733) IEA
  • positive regulation of interleukin-4 production (GO:0032753) IEA
Interleukin 20 receptor, β subunit is a component of the functional receptor heterodimers for interleukins 19, 20 and 24.
Interleukin 21 receptor
(IL-2 receptor family)
  • interleukin-21 receptor activity (GO:0001532) NAS
This is the ligand binding subunit of the functional heterodimeric receptor for interleukin 21.
Interleukin 22 receptor, α1 subunit
(IL-10 receptor family)
  • interferon receptor activity (GO:0004904) TAS
IL22RA1 is a subunit in the heterodimeric receptors for interleukins 20 and 24 (which bind to the interleukin-22α1/20β heteromer) and IL-22 (which binds to the interleukin-22α1/10β heteromer).
Interleukin-22 receptor α2
(IL-10 receptor family)
  • interleukin-22 receptor activity (GO:0042018) IDA
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 [55,64] ...
Interleukin 23 receptor
(IL-12 receptor family)
  • negative regulation of interleukin-10 production (GO:0032693) IMP
  • positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725) IC
  • positive regulation of interferon-gamma production (GO:0032729) IDA
  • positive regulation of interleukin-12 production (GO:0032735) IDA
  • positive regulation of interleukin-17 production (GO:0032740) IC
  • response to interferon-gamma (GO:0034341) IDA
  • interleukin-23-mediated signaling pathway (GO:0038155) IEA
This is one of the subunits of the functional IL-23 receptor heterodimer.
Interleukin 27 receptor, alpha
(IL-6 receptor family)
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • interleukin-27 receptor activity (GO:0045509) 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)
  • interleukin-2 receptor activity (GO:0004911) IBA
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-2 receptor subunit β
(IL-2 receptor family)
  • interleukin-2 receptor activity (GO:0004911) IDA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R.
Interleukin-2 receptor subunit γ
(IL-2 receptor family)
  • cytokine receptor activity (GO:0004896) IEA
  • interleukin-4-mediated signaling pathway (GO:0035771) IEA
  • interleukin-2-mediated signaling pathway (GO:0038110) IEA
  • interleukin-7-mediated signaling pathway (GO:0038111) IEA
IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor.
Interleukin-31 receptor, α subunit
(IL-6 receptor family)
  • cytokine receptor activity (GO:0004896) TAS
  • cytokine-mediated signaling pathway (GO:0019221) TAS
  • T-helper 2 cell cytokine production (GO:0035745) IEA
Interleukin 3 receptor, α subunit
(IL-3 receptor family)
  • interleukin-3 receptor activity (GO:0004912) TAS
This is the ligand binding subunit of the functional IL-3 receptor complex.
Interleukin-4 receptor subunit α
(IL-2 receptor family)
  • interleukin-4 receptor activity (GO:0004913) TAS
  • positive regulation of chemokine secretion (GO:0090197) IEA
IL4R is the common ligand binding subunit shared by the IL-4 receptors type I (receptor for IL-4) and type II (receptor for IL-4 and IL-13). A gain-of-function mutation in IL4R has been associated with atopy, enhanced B cell isotype switching from mu to epsilon and therefore elevated IgE levels [87] ...
Interleukin 5 receptor, α subunit
(IL-3 receptor family)
  • interleukin-5 receptor activity (GO:0004914) TAS
  • regulation of interleukin-5 production (GO:0032674) IEA
This is the ligand binding subunit of the functional IL-5 receptor complex.
Interleukin-6 receptor, α subunit
(IL-6 receptor family)
  • interleukin-6 receptor activity (GO:0004915) IEA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • negative regulation of interleukin-8 production (GO:0032717) NAS
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • response to cytokine (GO:0034097) IDA
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
  • ciliary neurotrophic factor-mediated signaling pathway (GO:0070120) IMP
IL6R polymorphisms are associated with asthma risk [65] ...
Interleukin-6 receptor, β subunit
(IL-6 receptor family)
  • ciliary neurotrophic factor receptor activity (GO:0004897) IDA
  • interleukin-11 receptor activity (GO:0004921) IEA
  • positive regulation of vascular endothelial growth factor production (GO:0010575) TAS
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • response to cytokine (GO:0034097) IDA
  • oncostatin-M-mediated signaling pathway (GO:0038165) IMP
  • interleukin-27 receptor activity (GO:0045509) IC
  • interleukin-6-mediated signaling pathway (GO:0070102) IMP
  • negative regulation of interleukin-6-mediated signaling pathway (GO:0070104) IDA
  • interleukin-27-mediated signaling pathway (GO:0070106) IMP
  • ciliary neurotrophic factor-mediated signaling pathway (GO:0070120) IDA
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)
  • interleukin-7 receptor activity (GO:0004917) TAS
This is the ligand binding subunit of the functional IL-7 receptor complex.
Interleukin 9 receptor
(IL-2 receptor family)
  • interleukin-9 receptor activity (GO:0004919) TAS
The functional IL-9 receptor is a heterodimer of the ligand binding IL-9 receptor subunit and the interleukin 2 receptor γ (IL2RG) subunit. IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, including those for interleukin-2, -4, -7, and -15. ...
KIT proto-oncogene receptor tyrosine kinase
(Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family)
  • dendritic cell cytokine production (GO:0002371) ISS
  • stem cell factor receptor activity (GO:0005020) IEA
  • cytokine-mediated signaling pathway (GO:0019221) IDA
  • mast cell cytokine production (GO:0032762) IDA
  • Kit signaling pathway (GO:0038109) IDA
  • erythropoietin-mediated signaling pathway (GO:0038162) ISS
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 [77] ...
lymphotoxin β receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
Interaction of the lymphotoxin β receptor with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [38] ...
macrophage stimulating 1 receptor
(Type X RTKs: HGF (hepatocyte growth factor) receptor family)
  • macrophage colony-stimulating factor receptor activity (GO:0005011) TAS
The role of RON in immuno-oncology is reviewed in [1] ...
MER proto-oncogene, tyrosine kinase
(Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family)
  • negative regulation of cytokine production (GO:0001818) IEA
Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [20,223] ...
NLRC3
(NOD-like receptor family)
  • negative regulation of interferon-alpha production (GO:0032687) ISS
  • negative regulation of interferon-beta production (GO:0032688) ISS
  • negative regulation of interleukin-6 production (GO:0032715) IDA
  • negative regulation of tumor necrosis factor production (GO:0032720) 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 [137,245] ...
NLRC4
(NOD-like receptor family)
  • interleukin-1 beta secretion (GO:0050702) IDA
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 [143] ...
NLRC5
(NOD-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • 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 [154] ...
NLRP10
(NOD-like receptor family)
  • positive regulation of interleukin-8 secretion (GO:2000484) IMP
  • positive regulation of interleukin-6 secretion (GO:2000778) IMP
NLRP10 is an intracellular pattern recognition receptor (PRR) that has apoptotic and anti-inflammatory functions [94] ...
NLRP3
(NOD-like receptor family)
  • interleukin-1 beta production (GO:0032611) IEA
  • interleukin-18 production (GO:0032621) IEA
  • positive regulation of interleukin-13 production (GO:0032736) IEA
  • positive regulation of interleukin-4 production (GO:0032753) ISS
  • positive regulation of interleukin-5 production (GO:0032754) IEA
  • interleukin-1 secretion (GO:0050701) IEA
  • negative regulation of interleukin-1 beta secretion (GO:0050713) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • 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 [12] ...
NLRX1
(NOD-like receptor family)
  • negative regulation of type I interferon production (GO:0032480) TAS
  • negative regulation of interferon-beta production (GO:0032688) IEA
  • negative regulation of interleukin-6 production (GO:0032715) IEA
  • negative regulation of RIG-I signaling pathway (GO:0039536) IEA
NLRX1 is an intracellular pattern recognition receptor that plays a role in host immunity to certain bacterial infections.
nucleotide binding oligomerization domain containing 1
(NOD-like receptor family)
  • positive regulation of interleukin-1 beta production (GO:0032731) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • interleukin-8 biosynthetic process (GO:0042228) IDA
NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety.
nucleotide binding oligomerization domain containing 2
(NOD-like receptor family)
  • cytokine production involved in immune response (GO:0002367) IMP
  • cytokine secretion involved in immune response (GO:0002374) IMP
  • positive regulation of dendritic cell cytokine production (GO:0002732) IEA
  • positive regulation of interleukin-1 beta production (GO:0032731) IMP
  • positive regulation of interleukin-10 production (GO:0032733) ISS
  • positive regulation of interleukin-17 production (GO:0032740) IMP
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IMP
  • positive regulation of tumor necrosis factor production (GO:0032760) IDA
  • positive regulation of interleukin-1 beta secretion (GO:0050718) 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)
  • cytokine receptor activity (GO:0004896) IEA
  • response to cytokine (GO:0034097) IDA
  • oncostatin-M-mediated signaling pathway (GO:0038165) IMP
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 ...
osteoprotegerin
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The protein product of the TNFRSF11B gene, osteoprotegerin, acts as a soluble decoy receptor for RANK ligand (RANKL) and for TRAIL. Experimental evidence links the RANK/RANKL signalling pathway with the inflammatory activation of microglial cells relevant in the development of infection-induced perinatal brain injury [109] ...
OX40
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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 [226] ...
receptor activator of NF-kappa B
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) ISS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) ISS
  • response to cytokine (GO:0034097) IMP
  • response to tumor necrosis factor (GO:0034612) ISS
  • response to interleukin-1 (GO:0070555) ISS
  • TNFSF11-mediated signaling pathway (GO:0071847) IMP
  • positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling (GO:0071848) IMP
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.
RELT
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
A regulatory role in the immune response is suggested by RELT's capacity to stimulate T-cell proliferation in the presence of CD3 signalling.
RTP Type C
(Receptor tyrosine phosphatase (RTP) family)
  • negative regulation of cytokine-mediated signaling pathway (GO:0001960) 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 [53] ...
TACI
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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).
TLR1
(Toll-like receptor family)
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) ISS
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) ISS
  • regulation of cytokine secretion (GO:0050707) IEA
TLR1/2 heterodimers detect and respond to bacterial triacyl lipopeptides [215] ...
TLR10
(Toll-like receptor family)
  • regulation of cytokine secretion (GO:0050707) 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 [162] ...
TLR2
(Toll-like receptor family)
  • cytokine secretion involved in immune response (GO:0002374) IMP
  • interleukin-10 production (GO:0032613) IDA
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interleukin-10 production (GO:0032733) IEA
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-18 production (GO:0032741) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • regulation of cytokine secretion (GO:0050707) IEA
TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [150] ...
TLR3
(Toll-like receptor family)
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of type III interferon production (GO:0034346) IEA
  • cellular response to interferon-beta (GO:0035458) IEA
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA
  • positive regulation of chemokine biosynthetic process (GO:0045080) IEA
  • positive regulation of interferon-alpha biosynthetic process (GO:0045356) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IDA
  • cellular response to interferon-gamma (GO:0071346) IEA
TLR3 is an endosomal anti-viral receptor [215] ...
TLR4
(Toll-like receptor family)
  • regulation of dendritic cell cytokine production (GO:0002730) IEA
  • interferon-gamma production (GO:0032609) IEA
  • negative regulation of interferon-gamma production (GO:0032689) ISS
  • negative regulation of interleukin-17 production (GO:0032700) ISS
  • negative regulation of interleukin-23 production (GO:0032707) ISS
  • negative regulation of interleukin-6 production (GO:0032715) ISS
  • negative regulation of tumor necrosis factor production (GO:0032720) ISS
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interferon-alpha production (GO:0032727) ISS
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interferon-gamma production (GO:0032729) ISS
  • positive regulation of interleukin-1 production (GO:0032732) ISS
  • positive regulation of interleukin-10 production (GO:0032733) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of tumor necrosis factor biosynthetic process (GO:0042535) IDA
  • positive regulation of interleukin-12 biosynthetic process (GO:0045084) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IEA
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IDA
  • interleukin-1 beta secretion (GO:0050702) ISS
  • regulation of cytokine secretion (GO:0050707) IEA
  • positive regulation of macrophage cytokine production (GO:0060907) IEA
TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [23,173] ...
TLR5
(Toll-like receptor family)
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • regulation of cytokine secretion (GO:0050707) IEA
TLR5 induces a pro-inflammatory response upon detection of extracellular bacterial flagellin from invading mobile bacteria [143] ...
TLR6
(Toll-like receptor family)
  • positive regulation of interleukin-6 biosynthetic process (GO:0045410) ISS
  • interleukin-1 beta secretion (GO:0050702) ISS
  • regulation of cytokine secretion (GO:0050707) IEA
TLR6 forms heterodimers with TLR2 to detect a wide range of bacterial lipopeptides from bacterial cell membranes, and effect an immune response [63] ...
TLR7
(Toll-like receptor family)
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA
  • positive regulation of interferon-alpha biosynthetic process (GO:0045356) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IDA
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IMP
TLR7 is an endosomal receptor detecting ssRNA [215] ...
TLR8
(Toll-like receptor family)
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA
  • positive regulation of interferon-alpha biosynthetic process (GO:0045356) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IDA
  • positive regulation of interleukin-8 biosynthetic process (GO:0045416) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
  • positive regulation of interleukin-6 secretion (GO:2000778) IDA
  • negative regulation of interleukin-12 secretion (GO:2001183) IDA
TLR8 is an endosomal receptor detecting ssRNA [215] ...
TLR9
(Toll-like receptor family)
  • tumor necrosis factor production (GO:0032640) IDA
  • negative regulation of interleukin-6 production (GO:0032715) ISS
  • negative regulation of interleukin-8 production (GO:0032717) IDA
  • positive regulation of chemokine production (GO:0032722) IDA
  • positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725) IDA
  • positive regulation of interferon-beta production (GO:0032728) ISS
  • positive regulation of interleukin-10 production (GO:0032733) ISS
  • positive regulation of interleukin-12 production (GO:0032735) ISS
  • positive regulation of interleukin-18 production (GO:0032741) ISS
  • positive regulation of interleukin-6 production (GO:0032755) IDA
  • positive regulation of interleukin-8 production (GO:0032757) IDA
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
  • positive regulation of interferon-gamma biosynthetic process (GO:0045078) IDA
  • positive regulation of interferon-alpha biosynthetic process (GO:0045356) IDA
  • positive regulation of interferon-beta biosynthetic process (GO:0045359) IDA
  • regulation of cytokine secretion (GO:0050707) IEA
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [215] ...
tumor necrosis factor receptor 1
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) TAS
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • cytokine-mediated signaling pathway (GO:0019221) ISS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IMP
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 [78,155] ...
tumor necrosis factor receptor 2
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-activated receptor activity (GO:0005031) IBA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
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 [78,155] ...
TWEAK receptor
(Tumour necrosis factor (TNF) receptor family)
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
The protein product of the TNFRSF12A gene (fibroblast growth factor-inducible 14, or TWEAK receptor) is a receptor for the endogenous ligand TNF-like weak inducer of apoptosis (TWEAK). TWEAK receptor expression is upregulated in response to tissue injury. TWEAK receptor activation results in modulation of expression of NF-κB-regulated genes associated with the resolution of tissue damage. Because of its proinflammatory signalling profile the TWEAK receptor/TWEAK system has been implicated in a number of pathologies, and is therefore considered a potential drug target for conditions including muscle atrophy, cerebral ischaemia [79] ...
Transporters
GtoPdb receptor name (family) Process Association Comments GO Associations Immunopharmacology Comments
NRAMP1
(SLC11 family of proton-coupled metal ion transporters)
  • negative regulation of cytokine production (GO:0001818) ISS
  • positive regulation of cytokine production (GO:0001819) ISS
  • T cell cytokine production (GO:0002369) ISS
  • interleukin-2 production (GO:0032623) ISS
  • interleukin-3 production (GO:0032632) ISS
  • positive regulation of interferon-gamma production (GO:0032729) ISS
  • response to interferon-gamma (GO:0034341) 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 [27,197-198] ...
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))
  • positive regulation of interleukin-1 beta production (GO:0032731) IDA
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) IDA
  • cellular response to interferon-beta (GO:0035458) IEA
  • interleukin-1 beta secretion (GO:0050702) IMP
  • positive regulation of interleukin-1 beta secretion (GO:0050718) IDA
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)
  • negative regulation of interleukin-10 production (GO:0032693) IDA
  • positive regulation of interleukin-12 production (GO:0032735) IMP
  • positive regulation of monocyte chemotactic protein-1 production (GO:0071639) IEA
RAGE is a single chain, membrane bound immunoglobulin type protein [153,187,237] ...
baculoviral IAP repeat containing 2
(Inhibitors of apoptosis (IAP) protein family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) TAS
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [116] ...
baculoviral IAP repeat containing 3
(Inhibitors of apoptosis (IAP) protein family)
  • regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
  • tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
  • regulation of RIG-I signaling pathway (GO:0039535) 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[181] ...
BCL2, apoptosis regulator
(B-cell lymphoma 2 (Bcl-2) protein family)
  • response to cytokine (GO:0034097) IDA
The role of Bcl-2 family members in immunity and disease is reviewed in [60] ...
Bcl-2-like 1
(B-cell lymphoma 2 (Bcl-2) protein family)
  • response to cytokine (GO:0034097) IDA
The role of Bcl-2 family members in immunity and disease is reviewed in [5] ...
CD2
(CD molecules)
  • positive regulation of tumor necrosis factor production (GO:0032760) IDA
  • positive regulation of interferon-gamma secretion (GO:1902715) IDA
  • positive regulation of interleukin-8 secretion (GO:2000484) IMP
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [240] ...
CD28
(CD molecules)
  • positive regulation of interleukin-10 production (GO:0032733) IDA
  • positive regulation of interleukin-4 production (GO:0032753) IDA
  • cytokine biosynthetic process (GO:0042089) TAS
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) IDA
CD28 is expressed on the surface of T cells and is required for the co-stimulaory 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). The B7 proteins CD80 and CD86 on the surface of antigen presenting cells bind CD28.
As a drug target, CD28 modulation is being investigated as a treatment for autoimmume conditions. In 2006 an anti-CD28 antbody with superagonist activity (TGN1412) caused catastrophic organ failure in clinical trial participants due to 'cytokine storm' (multiple cytokine-release syndrome) in response to massive systemic T cell activation and inflammatory response [205] ...
CD38
(CD molecules)
  • response to interleukin-1 (GO:0070555) IEA
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 [80] ...
CD3e
(CD molecules)
  • positive regulation of interferon-gamma production (GO:0032729) IEA
  • positive regulation of interleukin-4 production (GO:0032753) IEA
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) IEA
CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [56,199] ...
CD6
(CD molecules)
  • 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 [149] ...
CD74
(CD molecules)
  • positive regulation of cytokine-mediated signaling pathway (GO:0001961) IMP
  • cytokine receptor activity (GO:0004896) IDA
  • macrophage migration inhibitory factor signaling pathway (GO:0035691) IEA
  • positive regulation of macrophage cytokine production (GO:0060907) ISS
  • positive regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000343) ISS
CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [43] ...
CD80
(CD molecules)
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) NAS
  • positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process (GO:0045425) NAS
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ...
CD86
(CD molecules)
  • response to interferon-gamma (GO:0034341) IEA
  • positive regulation of lymphotoxin A biosynthetic process (GO:0043017) NAS
  • positive regulation of interleukin-2 biosynthetic process (GO:0045086) NAS
  • positive regulation of interleukin-4 biosynthetic process (GO:0045404) NAS
  • cellular response to cytokine stimulus (GO:0071345) IEA
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)
  • positive regulation of type I interferon production (GO:0032481) TAS
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ...
C-type lectin domain family 4 member E
(C-type lectin-like receptors (CLRs))
  • positive regulation of cytokine secretion (GO:0050715) 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)) [30] ...
C-type lectin domain family 6 member A
(C-type lectin-like receptors (CLRs))
  • positive regulation of cytokine secretion (GO:0050715) ISS
Dectin-2 is involved in initiating the innate immune response upon recognition of high mannose structures on fungal cell walls. It associates with the ITAM-containing FcRβ adaptor and signals through the Syk, PKCδ, and CARD9-Bcl10-MALT1 pathways to promote cytokine production in response ...
E1A binding protein p300
(Non-enzymatic BRD containing proteins)
  • positive regulation of type I interferon production (GO:0032481) 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 interleukin-3 biosynthetic process (GO:0045401) IEA
  • positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process (GO:0045425) 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 interleukin-10 production (GO:0032733) IEA
  • positive regulation of interleukin-6 production (GO:0032755) IEA
  • positive regulation of tumor necrosis factor production (GO:0032760) IEA
  • positive regulation of mast cell cytokine production (GO:0032765) IEA
heat shock protein 90 alpha family class B member 1
(Heat shock proteins)
  • regulation of interferon-gamma-mediated signaling pathway (GO:0060334) IMP
  • regulation of type I interferon-mediated signaling pathway (GO:0060338) IMP
  • cellular response to interleukin-4 (GO:0071353) IEA
  • negative regulation of transforming growth factor beta activation (GO:1901389) IDA
interferon gamma inducible protein 16
(Absent in melanoma (AIM)-like receptors (ALRs))
  • positive regulation of cytokine production (GO:0001819) TAS
  • positive regulation of type I interferon production (GO:0032481) TAS
  • positive regulation of interleukin-1 beta production (GO:0032731) 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)
  • negative regulation of interleukin-2 biosynthetic process (GO:0045085) IEA
LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [6] ...
leucine rich repeat containing 32
(Leucine-rich repeat proteins)
  • negative regulation of cytokine secretion (GO:0050710) 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 [46] ...
lymphocyte antigen 96
(Lymphocyte antigens)
  • positive regulation of tumor necrosis factor production (GO:0032760) ISS
LY96 (MD2) is a binding partner of Toll-like receptor 4 (TLR4), required to initiate an innate immune response to bacterial lipopolysaccharide (LPS). The signaling complex also contains CD14 co-receptor [112] ...
neural cell adhesion molecule 1 (CD56)
(CD molecules)
  • interferon-gamma-mediated signaling pathway (GO:0060333) TAS
CD56 is expressed by neurons, glia, skeletal muscle and natural killer (NK) cells. The CD56bright NK cell subset, predominantly present in secondary lymphoid tissues, are capable of high levels of cytokine production, are enriched at inflammatory sites [52] ...
programmed cell death 1 ligand 1 (CD274)
(CD molecules)
  • negative regulation of interferon-gamma production (GO:0032689) IMP
  • negative regulation of interleukin-10 production (GO:0032693) IMP
  • response to cytokine (GO:0034097) IDA
  • negative regulation of tumor necrosis factor superfamily cytokine production (GO:1903556) IMP
  • positive regulation of interleukin-10 secretion (GO:2001181) IDA
PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. Both the ligand and receptor are being pursued as targets for novel oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [164] ...
transmembrane protein 173
(Other pattern recognition receptors)
  • regulation of type I interferon production (GO:0032479) TAS
  • positive regulation of type I interferon production (GO:0032481) IDA
  • interferon-beta production (GO:0032608) IDA
  • cellular response to interferon-beta (GO:0035458) IEA
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) [14,31,95-96] ...