Targets Associated to Immuno Processes - Immune system development
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Targets Associated to Immuno Processes
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ |
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| GPCRs | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ADGRG3 (Adhesion Class GPCRs) |
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ADGRG3 is expressed by immune cells. It is required for proper B cell development in the spleen [317] ... | ||
| CCR1 (Chemokine receptors) |
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CCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR2 (Chemokine receptors) |
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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] ... | ||
| CCR4 (Chemokine receptors) |
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CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [279] ... |
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| CCR6 (Chemokine receptors) |
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CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [157,182] ... | ||
| CCR7 (Chemokine receptors) |
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CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CCR9 (Chemokine receptors) |
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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 [325] ... | ||
| CXCR5 (Chemokine receptors) |
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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. | ||
| EP4 receptor (Prostanoid receptors) |
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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 [345] ... | ||
| GPR183 (Class A Orphans) |
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Gpr183-deficient mice show a reduction in the early antibody response to a T-dependent antigen. GPR183-deficient B cells fail to migrate to the outer follicle and instead stay in the follicle centre [152,237] ... | ||
| GPR55 (GPR18, GPR55 and GPR119) |
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| Ion Channels | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| Cav1.2 (Voltage-gated calcium channels (CaV)) |
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Cav1.2 is implicated in Th2 cell function in asthma [259,308] ... | ||
| Nuclear Hormone Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| RAR-related orphan receptor-γ (1F. Retinoic acid-related orphans) |
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RORγ is a nuclear receptor transcription factor that acts as an immune cell master control switch (most likely associated with expression of the RORγt isoform). This receptor is an essential regulator of type 17 effector T cell differentiation and function. RORγt inhibitors (antagonists and inverse agonists) [72,98,218,282] ... | ||
| Retinoic acid receptor-γ (1B. Retinoic acid receptors) |
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Retinoid drugs reduce the proinflammatory factors and disrupt the immunoinflammatory cascade associated with acne vulgaris. RARγ is one of the molecular targets of anti-acne retinoid family drugs. RARγ-selective retinoid derivatives are being investigated as topical agents, which are exp ... | ||
| Enzymes | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
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Included in GtoImmuPdb based on its association with leukemia. | ||
| aconitate decarboxylase 1 (Itaconate biosynthesis) |
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Itaconate (itaconic acid) is generated from the citric acid (TCA) cycle intermediate cis-aconitic acid which is produced by mitochondria. Itaconate is synthesised by the enzyme aconitate decarboxylase 1 (referred to as immunoresponsive gene 1 or IRG1). Its synthesis links metabolism to immunity and it plays an important role in the macrophage-based immune response [67,80] ... | ||
| ADAM17 (M12: Astacin/Adamalysin) |
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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 [55] ... | ||
| ADAM8 (M12: Astacin/Adamalysin) |
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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) [235] ... | ||
| Adenosine deaminase (Adenosine turnover) |
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Adenosine deaminase deficiency causes immunodeficiency (ADA deficiency or ADA-SCID). Around 30 known genotypes are associated with this autosomal recessive metabolic disorder. Mitotically active cells such as developing T cells and B cells are susceptible to this deficiency, expaining the resulting ... | ||
| BLK proto-oncogene, Src family tyrosine kinase (Src family) |
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BLK is a B cell-specific kinase. In Blk knockout mice B cells develop normally and show unaltered in vitro activation and humoral immune responses to T cell-dependent and -independent antigens, a result which is indicative of functional redundancy of Blk in B cell development and immune responses [299] ... | ||
| B-Raf proto-oncogene, serine/threonine kinase (RAF family) |
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BRAFV600E- immuno-oncology [1] ... | ||
| Bruton tyrosine kinase (Tec family) |
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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 [24] ... | ||
| calcium/calmodulin dependent protein kinase IV (CAMK1 family) |
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CAMKIV has been implicated in the differentiation of Th17 cells, suggesting CAMKIV as a target for therapeutic intervention in Th17-driven autoimmune diseases [159] ... | ||
| Caspase 3 (C14: Caspase) |
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Defective caspase 3 expression in immune effector cells may influence susceptibility to Kawasaki disease, an acute vasculitis syndrome affecting small- and medium-sized arteries of infants and children [224] ... | ||
| Caspase 8 (C14: Caspase) |
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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 [191] ... | ||
| cathepsin L (C1: Papain) |
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Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics. | ||
| cyclin dependent kinase 6 (CDK4 subfamily) |
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Phenotypic abnormalities in CDK6 knockout mice suggest biological roles in addition to mitotic cell cycle regulation. Alternate roles include involvement in hematopoietic function and inhibition of T cell differentiation [109,233] ... | ||
| enhancer of zeste 2 polycomb repressive complex 2 subunit (2.1.1.43 Histone methyltransferases (HMTs)) |
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EZH2 is involved in hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis, with notable participation in regulating the differentiation and function of T cells. This role suggests potential applications in immune-mediated conditions, including autoimmune disorders [304] ... | ||
| IL2 inducible T cell kinase (Tec family) |
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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 [24] ... | ||
| indoleamine 2,3-dioxygenase 1 (1.13.11.- Dioxygenases) |
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The indoleamine 2,3 dioxygenase (IDO) branch of the kynurenine (KYN) pathway of tryptophan metabolism has been intensely studied in relation to immune tolerance and allergy. IDO is generally considered to be a tolerogenic, immunosuppressive enzyme, that is induced by IFN-γ. It provides a negative feedback pathway that limits uncontrolled immune responses. Its immunosuppressive actions arise from its promotion of tryptophan depletion, and elevation of KYN metabolite levels. The aryl hydrocarbon receptor serves as a receptor for KYN and should be considered when evaluating the IDO-KYN pathway in immune homeostasis and its potential to modulate innate and adaptive immune responses [158] ... | ||
| INPP5D (Inositol polyphosphate phosphatases) |
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SHIP1 activators are proposed as novel anti-inflammatory agents e.g. rosiptor (AQX-1125) which is in Phase 2 and 3 clinical trials [217,287] ... | ||
| interleukin 1 receptor associated kinase 3 (Interleukin-1 receptor-associated kinase (IRAK) family) |
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IRAK3 expression is restricted to monocytes and macrophages. | ||
| IP3 kinase B (Inositol 1,4,5-trisphosphate 3-kinases) |
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IP3 kinase B (ITPKB) as an essential mediator of T cell activation, whose inhibition is considered a novel approach to treat autoimmune disease [203] ... | ||
| Janus kinase 2 (Janus kinase (JakA) family) |
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JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [30,32,285] ... | ||
| Janus kinase 3 (Janus kinase (JakA) family) |
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Psoriatic skin samples show elevated JAK3 (and JAK1) expression, with signalling predominantly through STAT3 [8] ... | ||
| LCK proto-oncogene, Src family tyrosine kinase (Src family) |
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Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [228] ... | ||
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [94,97,303] ... | ||
| mitogen-activated protein kinase 1 (ERK subfamily) |
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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 [154,187] ... | ||
| mitogen-activated protein kinase 14 (p38 subfamily) |
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p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [111-112,171,236,251,321] ... | ||
| MMP14 (M10: Matrix metallopeptidase) |
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MMP14 is included in GtoImmuPdb based on its contribution to degradation of collagenous cartilage matrix in rheumatoid arthritis. An anti-MMP14 antibody, DX-2400 [79] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
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PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [116] ... | ||
| phosphoinositide-3-kinase regulatory subunit 1 (Phosphatidylinositol kinases) |
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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 [185] ... | ||
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
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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 [102,262] ... | ||
| protein kinase C alpha (Delta subfamily) |
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PKCα is included in GtoImmuPdb based on its GO immune process associations. | ||
| protein kinase C zeta (Iota subfamily) |
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PKCζ is included in GtoImmuPdb based on its GO process associations. | ||
| protein kinase, DNA-activated, catalytic subunit (Other PIKK family kinases) |
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Protein kinase, DNA-activated, catalytic polypeptide (DNA-PKcs) principally acts to repair DNA in a process called non-homologous end joining (NHEJ). NHEJ is required for V(D)J recombination (somatic recombination) in developing lymphocytes during the early stages of T and B cell maturation. DNA-PKc ... | ||
| protein kinase N1 (Protein kinase N (PKN) family) |
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Evidence suggests that PKN1 plays a role in modulation of the NF-κB signalling pathway. Specifically, in Salmonella infection, PKN1 is hijacked by a bacterial effector protein which results in inhibition of NF-κB-dependent gene expression (i.e. inhibition of production of the proinflammatory cytokines that would normally effect bacterial destruction and removal) [114] ... | ||
| protein tyrosine kinase 2 beta (Fak family) |
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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 [58] ... | ||
| protein tyrosine phosphatase non-receptor type 22 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
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PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [65] ... | ||
| receptor interacting serine/threonine kinase 1 (Receptor interacting protein kinase (RIPK) family) |
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RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [216,255,276,314] ... | ||
| receptor interacting serine/threonine kinase 2 (Receptor interacting protein kinase (RIPK) family) |
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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) [220] ... | ||
| receptor interacting serine/threonine kinase 3 (Receptor interacting protein kinase (RIPK) family) |
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RIPK1 and RIPK3 are involved in necroptosis and as such are critical regulators of inflammation and cell death [216,255,276,314] ... | ||
| serine/threonine kinase 11 (LKB subfamily) |
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Development of fatal TH2-dominant inflammatory symptoms in mice with a specific Stk11 knockout in their Treg cells, and experiments showing Stk11's role in the coordination of metabolic and functional fitness of Treg cells, suggest that this kinase acts as a crucial checkpoint that actively maintains Treg cell survival and homeostatic function [117,339] ... | ||
| spleen associated tyrosine kinase (Syk family) |
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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 [100,254] ... | ||
| vanin 1 (Hydrolases) |
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Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [295] ... | ||
| zeta chain of T cell receptor associated protein kinase 70 (Syk family) |
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ZAP-70 has much lower intrinsic enzyme activity than SYK, and expression is restricted to T cells and NK cells [13] ... | ||
| Catalytic Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| 4-1BB (Tumour necrosis factor (TNF) receptor family) |
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4-1BB is a costimulatory receptor that is highly expressed on both T cells and NK cells in the tumour environment. Since activation of 4-1BB produces an immunostimulatory effect that supports the immune cells involved in tumour control it is a target for immuno-oncology drug development [188] ... | ||
| AXL receptor tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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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 [110] ... | ||
| CD27 (Tumour necrosis factor (TNF) receptor family) |
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CD27 (TNFRSF7) is a co-stimulatory immune checkpoint molecule that is expressed on various immune cells, including T cells and NK (natural killer) cells. The endogenous ligand for CD27 is CD70. CD27 interacts with various TRAF adaptor proteins and apoptosis regulatory protein SIVA (SIVA1). It has been recognized as playing an important role in priming, enhancing and sustaining a productive anti-cancer (CD8 T cell) adaptive immune response. CD27 is an immuno-oncology target [43,309] ... | ||
| CD40 (Immune checkpoint catalytic receptors, Tumour necrosis factor (TNF) receptor family) |
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CD40 is a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF). It is expressed on a variety of immune cells, including macrophages, B cells, and dendritic cells (DCs). CD40 plays a key role in the activation of the immune system. Endogenous ligand is CD154 (C ... | ||
| Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
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The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors. | ||
| fms related receptor tyrosine kinase 3 (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
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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 [234] ... |
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| Granulocyte colony-stimulating factor receptor (Prolactin receptor family) |
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This nuclear receptor mediates the effects of the cytokine, colony stimulating factor 3 (CSF3). CSF3 regulates the production, differentiation, and function of granulocytes. | ||
| integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (Integrins) |
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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 [113] ... | ||
| Interleukin-12 receptor, β1 subunit (IL-12 receptor family) |
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This protein is a subunit of both the IL-12 and IL-23 cytokine receptors. | ||
| Interleukin-15 receptor subunit α (IL-2 receptor family) |
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This is the ligand binding subunit of the functional IL-15 receptor complex. | ||
| Interleukin-18 receptor 1 (Immunoglobulin-like family of IL-1 receptors) |
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Interleukin-18 1 protein (IL18R1) is the ligand binding subunit of the functional IL-18 receptor heterodimer. | ||
| Interleukin-1 receptor-like 2 (Immunoglobulin-like family of IL-1 receptors) |
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Interleukin-1 receptor-like 2 is one of the subunits of the functional receptor for IL-36. An antibody that mimics IL-36RA's antagonist activity at the IL-36 receptor (MAB92) has been described [96] ... |
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| Interleukin 23 receptor (IL-12 receptor family) |
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This is one of the subunits of the functional IL-23 receptor heterodimer. | ||
| Interleukin 27 receptor, alpha (IL-6 receptor family) |
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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) |
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IL2RA is a ligand binding component of the IL-2R complex. This subunit is the molecular target of the approved biologics daclizumab (including daclizumab beta) and basiliximab. Another anti-CD25 mAb, inolimomab, has received orphan drug designation from the EMA, for the treatment of graft-versus-host disease. Phase 3 findings for this drug and indication are reported in [278] ... | ||
| Interleukin-2 receptor subunit γ (IL-2 receptor family) |
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IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor. | ||
| Interleukin-4 receptor subunit α (IL-2 receptor family) |
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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 [119] ... | ||
| Interleukin-6 receptor, α subunit (IL-6 receptor family) |
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IL6R polymorphisms are associated with asthma risk [90] ... | ||
| Interleukin-7 receptor subunit α (IL-2 receptor family) |
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This is the ligand binding subunit of the functional IL-7 receptor complex. Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [246] ... |
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| KIT proto-oncogene, receptor tyrosine kinase (Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family) |
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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 [108] ... | ||
| lymphotoxin β receptor (Tumour necrosis factor (TNF) receptor family) |
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Interaction of the lymphotoxin β receptor (LTBR) with its ligand is required for the development and organization of the secondary lymphoid organs and is involved in chemokine release (reported to induce interleukin 8 gene expression [57] ... | ||
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [22,316] ... | ||
| NLRP3 (NOD-like receptor family) |
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NLRP3 is a component of the NLRP3 inflammasome, a protein complex which activates caspase-1, and plays an important role in the regulation of inflammation and apoptosis (pyroptosis). Drug-like NLRP3 inhibitors are under investigation as novel therapeutics for the treatment of autoinflammatory diseases and neuroinflammation, as an alternative to anti-IL-1 therapies such as |
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| osteoprotegerin (Tumour necrosis factor (TNF) receptor family) |
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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 [153] ... | ||
| receptor activator of NF-kappa B (Tumour necrosis factor (TNF) receptor family) |
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RANK is the receptor for RANK-ligand (RANKL). It is associated with immune cell function and lymph node development, in addition to bone remodeling and repair, thermal regulation, and mammary gland development. Signals to NF-κB and JNK via TRAF adaptor proteins. | ||
| RTP Type C (Receptor tyrosine phosphatase (RTP) family) |
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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 [73] ... | ||
| TLR3 (Toll-like receptor family) |
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TLR3 is an endosomal anti-viral receptor [306] ... | ||
| TLR4 (Toll-like receptor family) |
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TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [33,247] ... | ||
| TLR9 (Toll-like receptor family) |
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TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [306] ... | ||
| transforming growth factor beta receptor 1 (Type I receptor serine/threonine kinases) |
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The role of TGFBR1 in immuno-oncology is reviewed in [1] ... | ||
| TYRO3 protein tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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TYRO3 is a negative regulator of type 2 immunity [56] ... | ||
| Transporters | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| Peptide transporter 4 (SLC15 family of peptide transporters) |
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SLC15A4 is an oligopeptide transporter that is expressed in early endosomes, and which is involved in NOD1-dependent NF-κB signaling [170] ... | ||
| Other Protein Targets | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| advanced glycosylation end-product specific receptor (Immunoglobulin like domain containing proteins) |
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RAGE is a single chain, membrane bound immunoglobulin type protein [214,266,337] ... | ||
| amyloid P component, serum (Serum pentraxins) |
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Serum amyloid P or pentraxin 2 is a multi-function circulating plasma protein. It exhibits activity as a soluble pattern recognition receptor of the innate immune system, that can bind DNA and histones when these are released from damaged cells. A recombinant form of human pentraxin 2 (PRM-151; Promedior) has been reported as an anti-fibrotic immunomodulator [84] ... |
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| BCL2 apoptosis regulator (B-cell lymphoma 2 (Bcl-2) protein family) |
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The role of Bcl-2 family members in immunity and disease is reviewed in [82] ... | ||
| BCL6 transcription repressor (BTB (POZ) domain containing TFs) |
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BCL6/corepressor complexes are important for the formation of germinal centers and differentiation and proliferation of lymphocytes. Oncogenic mutations in BCL6 lead to the development of diffuse large B-cell lymphoma cells from germinal center B cells. Disruption of BCL6/corepressor complex formation by pharmacological inhibitors has therefore been identified as a novel drug mechanism with potential for the treatment of autoimmune diseases and cancer [49,54] ... | ||
| CD19 (CD molecules) |
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CD19 is a B cell antigen used as a biomarker for normal and neoplastic B cells, and follicular dendritic cells. Anti-CD19 monoclonal antibodies are being investigated for potential clinical utility in oncology, transplantation and autimmune diseases (e.g. inebilizumab ... | ||
| CD1d molecule (CD molecules) |
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CD1d is a lipid-binding MHC class I-like protein that is expressed by dendritic cells. CD1d presents self and microbial lipid/glycolipid antigens to unconventional T cells known as invariant natural killer T (iNKT) cells [61,332] ... | ||
| CD2 (CD molecules) |
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CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [338] ... | ||
| CD20 (membrane-spanning 4-domains, subfamily A, member 1) (CD molecules) |
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CD20 is a B cell antigen, involved in B cell development and maturation to antibody-producing plasma cells [68] ... | ||
| CD28 (Other immune checkpoint proteins, CD molecules) |
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CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [5] ... | ||
| CD3e (CD molecules) |
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CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain). CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [74,284] ... |
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| CD4 (CD molecules) |
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CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [161,312] ... | ||
| CD74 (CD molecules) |
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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 [69] ... | ||
| CD79B (CD molecules) |
|
CD79B is a component of the multimeric B cell antigen receptor (along with CD79A and a membrane-bound antibody that acts as the antigen recognition moiety). The CD79A/B component is responsible for signal transduction. The B cell antigen receptor complex is reported to be involved in the pathogenesis of various B cell-derived lymphoid cancers [207,269] ... | ||
| CD80 (Other immune checkpoint proteins, CD molecules) |
|
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ... | ||
| CD86 (Other immune checkpoint proteins, CD molecules) |
|
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 ... | ||
| claudin 18 (Claudins) |
|
Claudin-18.1 is expressed exclusively in the tight junctions of lung epithelia. Claudin-18 deficiency has been identified as a contributor to airway epithelial barrier dysfunction and asthmatic reactions to air-borne antigens [294] ... | ||
| C-type lectin domain family 4 member E (C-type lectin-like receptors (CLRs)) |
|
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)) [42] ... | ||
| cytotoxic T-lymphocyte-associated protein 4 (CD152) (Other immune checkpoint proteins, CD molecules) |
|
CTLA-4 is expressed almost exclusively on CD4+ and CD8+ T cells. It functions as an immune checkpoint providing an inhibitory signal as a balance to stimulatory signals of the immune response i.e. it plays a crucial role in the maintenance of T cell homeostasis [201] ... | ||
| E1A binding protein p300 (Non-enzymatic BRD containing proteins) |
|
CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. PMID: 26261308 ... | ||
| forkhead box N1 (Forkhead box TFs) |
|
FOXN1 deficiency has been identified as the cause of the nude severe combined immunodeficiency (SCID) phenotype in mice and humans [95,240] ... | ||
| ICOS (CD278) (Other immune checkpoint proteins, CD molecules) |
|
Inducible T cell costimulator (ICOS) and it's ligand constitute an immune checkpoint. ICOS is a surface receptor on activated T cells that binds its ligand on antigen presenting cells. Ligand-receptor interaction is a T cell activation signal. ICOS is a major regulator of the adaptive immune reponse that is structurally and functionally related to CD28 [129] ... | ||
| killer cell lectin like receptor C1 (CD159a) (CD molecules) |
|
NKG2A (KLRC1; CD159a) acts as an inhibitory checkpoint receptor for HLA-E. NKG2A forms functional heterodimers with CD94 (KLRD1) to form a human leukocyte antigen E (HLA-E) recognition complex on a subset of natural killer (NK) cells and cytotoxic T cells. NKG2A/CD94/HLA-E binding suppresses immune vigilance, and overexpression of HLA-E is used by cancer cells to evade immune recognition and destruction [78,176,190,277] ... | ||
| LAG3 (CD223) (Other immune checkpoint proteins, CD molecules) |
|
Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [10,106] ... | ||
| leukocyte immunoglobulin like receptor B1 (CD85j) (CD molecules, Other immune checkpoint proteins) |
|
LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [44] ... | ||
| MALT1 paracaspase (Immunoglobulin like domain containing proteins) |
|
MALT1 inhibition is considered a tractable mechanism for the treatment of severe autoimmune diseases. The MALT1 inhibitory action of |
||
| NFKB inhibitor zeta (NF-κB regulators) |
|
IκBζ is a key component of the immune response that regulates the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. IκBζ acts as an inhibitor of primary NF-κB response genes, but may also act as a coactivator of the expression of secondary response genes (through association with the NF-κB p50 subunit). IκBζ is in fact the product of a primary NF-κB reponse gene, being rapidly upregulated by various inflammatory stimuli. Pro-inflammatory gene products that are regulated by IκBζ include CCL2, IL-6, IL12p40, IL-17, IFNγ, and GM-CSF [139,151] ... | ||
| polybromo 1 (Non-enzymatic BRD containing proteins) |
|
We have included PBRM1 in GtoImmuPdb as its repression has been reported to re-sensitise tumour cells with acquired resistance to immunotherapy (e.g. checkpoint blockade by anti-PD-1 or anti-CTLA-4 mAbs) to T cell-mediated attack [229] ... | ||
| programmed cell death 1 (CD279) (Other immune checkpoint proteins, CD molecules) |
|
Immune checkpoint blockade in oncology: Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [227] ... |
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| RAS guanyl releasing protein 1 (EF-hand domain containing proteins) |
|
RAS guanyl releasing protein 1 (RASGRP1) functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor. It activates Ras and the downstream Erk/MAP kinase cascade. RASGRP1 regulates the development, homeostasis and differentiation of T aand B cells [107,249,273] ... | ||
| signal transducer and activator of transcription 3 (STAT transcription factors) |
|
STAT3 regulates the expression of a variety of genes in response to cytokines and growth factors (e.g. IFNs, EGF, IL-5, IL-6, HGF, LIF and BMP2) and plays important roles in several cellular processes, including cell growth and apoptosis. STAT3 is a crucial component of the JAK/STAT signalling pathway that is implicated in cancer and inflammation. STAT3 is frequently activated in cancers, where it downmodulates intrinsic immune surveillance of tumour cells. Phosphorylated (activated) STAT3 (pSTAT3) is a marker of poor cancer prognosis [347,354] ... | ||
| signal transducer and activator of transcription 6 (STAT transcription factors) |
|
STAT6 plays a central role in exerting IL-4 mediated biological responses. The prosurvival activity of the Th2 cytokine IL-4 is mediated by STAT6-dependent transcription of the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL). This mechanism explains the resistance to apoptosis that is observed epithelial tumours which produce IL-4 [302] ... | ||
| TIM3 (CD366) (Other immune checkpoint proteins, CD molecules) |
|
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [205] ... | ||
| V-set immunoregulatory receptor (Other immune checkpoint proteins) |
|
V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [178] ... | ||
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