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Antigen presentation | Download as CSV | |||
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 | |
5-HT1B receptor (5-Hydroxytryptamine receptors) |
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The expression of 5-HT1B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [148] ... | ||
5-HT2B receptor (5-Hydroxytryptamine receptors) |
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The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [148] ... | ||
ACKR2 (Chemokine receptors) |
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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) |
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ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. ACKR3 binds the chemokine CXCL12 (stromal cell-derived factor 1, SDF-1 which is also a ligand for CXCR4). ACKR3 is an atypical receptor in that it does not activate G-protein-mediated signaling but induces β-arrestin recruitment [72] ... | ||
ACKR4 (Chemokine receptors) |
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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. | ||
β2-adrenoceptor (Adrenoceptors) |
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β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [42] ... | ||
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. | ||
CXCR1 (Chemokine receptors) |
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CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [3] ... | ||
CXCR2 (Chemokine receptors) |
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CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [3] ... | ||
D2 receptor (Dopamine receptors) |
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D2 receptor-mediated anti-inflammatory effects in the kidney have a protective effect. In contrast, impaired D2 receptor function results in renal inflammation and organ damage [164] ... | ||
EP3 receptor (Prostanoid receptors) |
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Foudi et al. (2012) [47] ... | ||
FPR2 (Formylpeptide receptors, Leukotriene receptors) |
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Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [147] ... | ||
PAR2 (Proteinase-activated receptors) |
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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) [49] ... | ||
Ion Channels | ||||
GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
nicotinic acetylcholine receptor α7 subunit (Nicotinic acetylcholine receptors (nACh)) |
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [143] ... | |||
Nuclear Hormone Receptors | ||||
GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
Liver X receptor-α (1H. Liver X receptor-like receptors) |
Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [156] ... | |||
Liver X receptor-β (1H. Liver X receptor-like receptors) |
Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses. LXRs are drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with therapeutic potential in neurodegenerative diseases [156] ... | |||
Peroxisome proliferator-activated receptor-γ (1C. Peroxisome proliferator-activated receptors) |
PPARγ agonists have anti-inflammatory effects. Full PPARγ agonists can cause undesireable weight gain, but partial agonists are devoid of this adverse effect and retain the anti-inflammatory effects of PPARγ modulation. The PPARγ agonist |
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Enzymes | ||||
GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
Included in GtoImmuPdb based on its association with leukemia. | |||
autotaxin (LPA synthesis) |
Autotaxin is up-regulated in many inflammatory conditions, including cancer, arthritis, fibrotic diseases and multiple sclerosis. The product of autotaxin activity, LPA, has proliferative, chemotactic and angiogenic actions. Inhibitors of the ATX-LPA axis are being investigated as novel pharmaceuticals [32] ... | |||
beta adrenergic receptor kinase 1 (Beta-adrenergic receptor kinases (βARKs)) |
GRK2 (βARK1) expression and activity are downregulated in lymphocytes from RA patients [92] ... | |||
cathepsin H (C1: Papain) |
Cathepsin H may act as a pro-granzyme B convertase [40] ... | |||
cathepsin L (C1: Papain) |
Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics. | |||
cathepsin S (C1: Papain) |
Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [135] ... | |||
component of inhibitor of nuclear factor kappa B kinase complex (IKK family) |
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 [66] ... | |||
Haem oxygenase 1 (Haem oxygenase) |
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 [7] ... |
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inhibitor of nuclear factor kappa B kinase subunit beta (IKK family) |
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) [15,17,129] ... | |||
mitogen-activated protein kinase 1 (ERK subfamily) |
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 [76,94] ... | |||
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
The role of PI3Kγ in immuno-oncology is reviewed in [3] ... | |||
PLCγ2 (Phosphoinositide-specific phospholipase C) |
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 [53,120] ... | |||
proteasome 20S subunit beta 8 (T1: Proteasome) |
PSMB8 is a component of the immunoproteasome [45] ... | |||
protein kinase C alpha (Delta subfamily) |
PKCα is included in GtoImmuPdb based on its GO immune process associations. | |||
protein tyrosine phosphatase non-receptor type 1 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
Inhibition of PTPN1/2 promotes T cell-mediated anti-tumour immunity [14,90,166] ... | |||
RAB27A, member RAS oncogene family (RAB subfamily) |
Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [70] ... | |||
sphingosine kinase 1 (Sphingosine kinase) |
The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [125-126] ... | |||
spleen associated tyrosine kinase (Syk family) |
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 [51,116] ... | |||
SRC proto-oncogene, non-receptor tyrosine kinase (Src family) |
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 [93] ... | |||
Catalytic Receptors | ||||
GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
AXL receptor tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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 [58] ... | |||
Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
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) |
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 [109] ... |
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integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (Integrins) |
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 [59] ... | |||
integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit) (Integrins) |
ITGB2 is the beta component of the β2 integrins. It forms αβ heterodimers with the CD11 alpha subunits ITGAL (αL aka CD11a forming integrin LFA-1), ITGAM (αM aka CD11b, forming integrin Mac-1) and ITGAX (αX aka CD11c, forming integrin p150/95). Beta2-integrins are essential for leukocyte extravasation to sites of infection (i.e. leukocyte trafficking), and other immunological processes including neutrophil phagocytosis and ROS production, and T cell activation. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [78] ... | |||
Interleukin 10 receptor, α subunit (IL-10 receptor family) |
Interleukin 10 receptor, α subunit is a component of the functional IL-10 receptor heterodimer. | |||
nucleotide binding oligomerization domain containing 1 (NOD-like receptor family) |
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. Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ ... |
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nucleotide binding oligomerization domain containing 2 (NOD-like receptor family) |
NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP). Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ... |
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Transporters | ||||
GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
ABCB3 (ABCB subfamily) |
TAP1 (ABCB2) and TAP2 (ABCB3) form a transporter that plays an important role in antigen presentation by major histocompatibility complex class I (MHCI) molecules in the adaptive immune response [127] ... | |||
NRAMP1 (SLC11 family of proton-coupled metal ion transporters) |
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 [25,130-131] ... | |||
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) |
RAGE is a single chain, membrane bound immunoglobulin type protein [102,123,158] ... | |||
Bcl-2-like 1 (B-cell lymphoma 2 (Bcl-2) protein family) |
The role of Bcl-2 family members in immunity and disease is reviewed in [5] ... | |||
CD1d molecule (CD molecules) |
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 [34,153] ... | |||
CD209 molecule (C-type lectin-like receptors (CLRs)) |
DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response. | |||
CD22 (Other immune checkpoint proteins, CD molecules, SIGLECs (conserved)) |
CD22 (SIGLEC2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation, mediates B cell-B cell interactions and may be involved in the localisation of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via | |||
CD300a (CD molecules) |
CD300a is a member of the CD300 family of leucocyte surface receptors [20] ... | |||
CD6 (CD molecules) |
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 [99] ... | |||
CD74 (CD molecules) |
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 [38] ... | |||
C-type lectin domain family 4 member A (C-type lectin-like receptors (CLRs)) |
CLEC4A is an pattern recognition receptor and immunoreceptor that functions in cell adhesion, cell-cell signalling, glycoprotein turnover, and plays roles in inflammation and the immune response. It contains a immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. | |||
C-type lectin domain family 7 member A (C-type lectin-like receptors (CLRs)) |
Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [26] ... | |||
Fc fragment of IgG receptor and transporter (Immunoglobulin C1-set domain-containing proteins) |
FcRn is important for developing immunity in the fetus and neonate (transporting IgG from mother to fetus and neonate for passive immunity) [71] ... | |||
heat shock protein 90 beta family member 1 (Heat shock proteins) |
HSP90B1 is an endoplasmic reticulum chaperone required for proper folding and cell surface export of newly synthesized Toll-like receptor and integrin (CD11a, CD18 and CD49d) proteins. In its absence TLR responses are ablated, and there is no innate response to microbial stimuli [115] ... | |||
immunoglobulin heavy constant epsilon (Immunoglobulins) |
IgE is being investigated as a molecular target in allergic inflammatory conditions such as asthma, allergic rhinitis and chronic spontaneous urticaria. One anti-IgE monoclonal, omalizumab, has already been approved for use in patients with asthma or chronic spontaneous urticaria. Omalizumab binds t ... | |||
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 [5,56] ... | |||
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) [27] ... | |||
sialic acid binding Ig like lectin 8 (CD33-related SIGLECs) |
SIGLEC8 is a single-pass type I membrane protein. It is a member of the CD33-like subgroup of SIGLECs, and like the other members of this subgroup it carries a conserved cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) which facilitates its role as an inhibitory receptor on the surface of mast cells and eosinophils [46,74] ... | |||
SIRPA (CD172a) (CD molecules, Signal regulatory proteins) |
SIRPα is an important inhibitory immune response regulator. In interaction with CD47, SIRPα controls an inhibitory innate immune checkpoint that provides an anti-phagocytic (do not eat) signal. SIRPα is predominantly expressed by macrophages. Laboratory work has established that SIRPα is expressed by a subset of intestinal dendritic cells (integrin CD103+ DCs) that are critical for maintaining intestinal (mucosal) immune system homeostasis. This subset of CD103+SIRPα+ DCs selectively activates Th17 cells and type 3 innate lymphoid cells (ILC3) [69,149] ... | |||
unc-119 lipid binding chaperone (Lipid binding chaperones) |
UNC119's role in regulating lymphocyte-specific protein tyrosine kinase (Lck) activity has been reported to be essential for the formation of immunological synapses and activation of T cells [57] ... |