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University of Dundee

The Concise Guide to PHARMACOLOGY 2015/16

Alexander, Stephen P. H.; Fabbro, Doriano; Kelly, Eamonn; Marrion, Neil; Peters, John A.;Benson, Helen E.Published in:British Journal of Pharmacology

DOI:10.1111/bph.13353

Publication date:2015

Document VersionPublisher's PDF, also known as Version of record

Link to publication in Discovery Research Portal

Citation for published version (APA):Alexander, S. P. H., Fabbro, D., Kelly, E., Marrion, N., Peters, J. A., Benson, H. E., Faccenda, E., Pawson, A. J.,Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators (2015). The Concise Guide toPHARMACOLOGY 2015/16: Catalytic receptors. British Journal of Pharmacology, 172(24), 5979-6023.https://doi.org/10.1111/bph.13353

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S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. British Journal of Pharmacology (2015) 172, 5979–6023

THE CONCISE GUIDE TO PHARMACOLOGY 2015/16:Catalytic receptors

Stephen PH Alexander1, Doriano Fabbro2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5,Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5

and CGTP Collaborators

1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK2PIQUR Therapeutics, Basel 4057, Switzerland3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK

Abstract

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebaseof drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gatedion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on thebest available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets.It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presentedin the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classificationand nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable,point-in-time record that will survive database updates.

Conflict of interest

The authors state that there are no conflicts of interest to declare.

c 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Overview: Catalytic receptors are cell-surface proteins, usuallydimeric in nature, which encompass ligand binding and func-tional domains in one polypeptide chain. The ligand bindingdomain is placed on the extracellular surface of the plasma mem-brane and separated from the functional domain by a singletransmembrane-spanning domain of 20-25 hydrophobic aminoacids. The functional domain on the intracellular face of theplasma membrane has catalytic activity, or interacts with partic-ular enzymes, giving the superfamily of receptors its name. En-

dogenous agonists of the catalytic receptor superfamily are pep-tides or proteins, the binding of which may induce dimerizationof the receptor, which is the functional version of the receptor.Amongst the catalytic receptors, particular subfamilies may bereadily identified dependent on the function of the enzymaticportion of the receptor. The smallest group is the particulateguanylyl cyclases of the natriuretic peptide receptor family. Themost widely recognized group is probably the receptor tyrosinekinase (RTK) family, epitomized by the neurotrophin receptor

family, where a crucial initial step is the activation of a signallingcascade by autophosphorylation of the receptor on intracellulartyrosine residue(s) catalyzed by enzyme activity intrinsic to thereceptor. A third group is the extrinsic protein tyrosine kinasereceptors, where the catalytic activity resides in a separate pro-tein from the binding site. Examples of this group include theGDNF and ErbB receptor families, where one, catalytically silent,member of the heterodimer is activated upon binding the ligand,causing the second member of the heterodimer, lacking ligand

Searchable database: http://www.guidetopharmacology.org/index.jsp Catalytic receptors 5979

Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=862http://www.guidetopharmacology.orghttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/fullhttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/fullhttp://www.guidetopharmacology.orghttp://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


binding capacity, to initiate signaling through tyrosine phos-phorylation. A fourth group, the receptor threonine/serine ki-nase (RTSK) family, exemplified by TGF-β and BMP receptors,has intrinsic serine/threonine protein kinase activity in the het-

erodimeric functional unit. A fifth group is the receptor ty-rosine phosphatases (RTP), which appear to lack cognate lig-ands, but may be triggered by events such as cell:cell contactand have identified roles in the skeletal, hematopoietic and

immune systems.A sixth group of catalytic receptors in the Guide is the integrins,which have roles in cell:cell communication, often associatedwith signaling in the blood.

Family structure

5981 Cytokine receptor family

5981 IL-2 receptor family




5985 Prolactin receptor family

5986 Interferon receptor family


5988 Immunoglobulin-like family of IL-1 receptors


5990 GDNF receptor family

5991 Integrins

5994 Natriuretic peptide receptor family

5996 Pattern recognition receptors

5996 Toll-like receptor family

5997 NOD-like receptor family– Receptor kinases– Other protein kinases– TK: Tyrosine kinase

5999 Receptor serine/threonine kinase (RSTK) family

6000 Type I receptor serine/threonine kinases

6001 Type II receptor serine/threonine kinases

6001 Type III receptor serine/threonine kinases

6002 RSTK functional heteromers

6003 Receptor tyrosine kinases6004 Type I RTKs: ErbB (epidermal growth factor)

receptor family

6005 Type II RTKs: Insulin receptor family

6005 Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family6007 Type IV RTKs: VEGF (vascular endothelial growth factor)

receptor family

6008 Type V RTKs: FGF (fibroblast growth factor)receptor family

6008 Type VI RTKs: PTK7/CCK4

6009 Type VII RTKs: Neurotrophin receptor/Trk family

6010 Type VIII RTKs: ROR family

6010 Type IX RTKs: MuSK

6010 Type X RTKs: HGF (hepatocyte growth factor)receptor family

6011 Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK)receptor family

6012 Type XII RTKs: TIE family of angiopoietin receptors

6012 Type XIII RTKs: Ephrin receptor family

6013 Type XIV RTKs: RET

6014 Type XV RTKs: RYK

6014 Type XVI RTKs: DDR (collagen receptor) family

6015 Type XVII RTKs: ROS receptors

6015 Type XVIII RTKs: LMR family6016 Type XIX RTKs: Leukocyte tyrosine kinase (LTK)

receptor family

6016 Type XX RTKs: STYK1– TKL: Tyrosine kinase-like

6017 Receptor tyrosine phosphatases (RTP)

6018 Tumour necrosis factor (TNF) receptor family

Searchable database: http://www.guidetopharmacology.org/index.jsp Catalytic receptors 5980


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=699http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=683http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=686http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=687http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


Cytokine receptor familyCatalytic receptors! Cytokine receptor familyOverview: Cytokines are not a clearly defined group of agents,other than having an impact on immune signalling pathways, al-though many cytokines have effects on other systems, such as indevelopment. A feature of some cytokines, which allows themto be distinguished from hormones, is that they may be pro-duced by “non-secretory” cells, for example, endothelial cells.Within the cytokine receptor family, some subfamilies may beidentified, which are described elsewhere in the Guide to PHAR-MACOLOGY, receptors for the TNF family, the TGF-β family andthe chemokines. Within this group of records are described TypeI cytokine receptors, typified by interleukin receptors, and Type IIcytokine receptors, exemplified by interferon receptors. These re-ceptors possess a conserved extracellular region, known as the cy-tokine receptor homology domain (CHD), along with a range ofother structural modules, including extracellular immunoglobu-lin (Ig)-like and fibronectin type III (FBNIII)-like domains, a trans-

membrane domain, and intracellular homology domains. An un-usual feature of this group of agents is the existence of solubleand decoy receptors. These bind cytokines without allowing sig-nalling to occur. A further attribute is the production of endoge-nous antagonist molecules, which bind to the receptors selec-tively and prevent signalling. A commonality of these families ofreceptors is the ligand-induced homo- or hetero-oligomerisation,which results in the recruitment of intracellular protein part-ners to evoke cellular responses, particularly in inflammatory orhaematopoietic signalling. Although not an exclusive signallingpathway, a common feature of the majority of cytokine recep-tors is activation of the JAK/STAT pathway. This cascade is basedaround the protein tyrosine kinase activity of the Janus kinases(JAK), which phosphorylate the receptor and thereby facilitatethe recruitment of signal transducers and activators of transcrip-tion (STATs). The activated homo- or heterodimeric STATs func-

tion principally as transcription factors in the nucleus.

Type I cytokine receptors are characterized by two pairs ofconserved cysteines linked via disulfide bonds and a C-terminalWSXWS motif within their CHD. Type I receptors are commonlyclassified into five groups, based on sequence and structual ho-mology of the receptor and its cytokine ligand, which is poten-tially more reflective of evolutionary relationships than an earlierscheme based on the use of common signal transducing chainswithin a receptor complex. These are the IL-2, IL-3, IL-6, IL-12and prolactin families.

Type II cytokine receptors also have two pairs of conservedcysteines but with a different arrangement to Type I and also lackthe WSXWS motif. The type II cytokine receptors include the in-terferon, IL-10, IL-1 and IL-17 receptors.

IL-2 receptor familyCatalytic receptors! Cytokine receptor family! IL-2 receptor familyOverview: The IL-2 receptor family consists of one or more ligand-selective subunits, and a common γ chain (γc): IL2RG, P31785), though IL-4 and IL-7 receptors can form complexes with other receptorchains. Receptors of this family associate with Jak1 and Jak3, primarily activating Stat5, although certain family members can also activate Stat1, Stat3, or Stat6. Ro264550 has been described as a selectiveIL-2 receptor antagonist, which binds to IL-2 [177].

Nomenclature Interleukin-2 receptor Interleukin-4 receptor type I Interleukin-4 receptor type II Interleukin-7 receptor Interleukin-9 receptor

Subunits Interleukin-2 receptor subunit β(Ligand-binding subunit),Interleukin-2 receptor subunit γ(Other subunit),Interleukin-2 receptor subunit α(Ligand-binding subunit)

Interleukin-4 receptor subunit α(Ligand-binding subunit),Interleukin-2 receptor subunit γ(Other subunit)

Interleukin-13 receptor subunit α1(Other subunit),Interleukin-4 receptor subunit α(Ligand-binding subunit)

Interleukin-2 receptor subunit γ(Other subunit),Interleukin-7 receptor subunit α(Ligand-binding subunit)

Interleukin-2 receptor subunit γ(Other subunit),Interleukin 9 receptor(Ligand-binding subunit)

Endogenous agonists IL-2 (IL2, P60568) IL-4 (IL4, P05112) IL-13 (IL13, P35225), IL-4 (IL4,P05112)

IL-7 (IL7, P13232) IL-9 (IL9, P15248)

Endogenous antagonists IL-1 receptor antagonist (IL1RN,P18510)

– – – –

Antagonists Ro26-4550 [177] – – – –

Selective antagonists AF12198 [3] – – – –

Searchable database: http://www.guidetopharmacology.org/index.jsp IL-2 receptor family 5981


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Nomenclature Interleukin 13 receptor, α2 Interleukin-15 receptor Interleukin-21 receptor Thymic stromal lymphopoietin receptor

HGNC, UniProt IL13RA2, Q14627 – – –

Subunits – Interleukin-2 receptor subunit β(Ligand-binding subunit),Interleukin-15 receptor subunit α(Ligand-binding subunit),Interleukin-2 receptor subunit γ (Othersubunit)

Interleukin-2 receptor subunit γ (Othersubunit), Interleukin 21 receptor(Ligand-binding subunit)

Cytokine receptor-like factor 2 (Othersubunit), Interleukin-7 receptor subunit α(Ligand-binding subunit)

Endogenous agonists – IL-15 (IL15, P40933) IL-21 (IL21, Q9HBE4) thymic stromal lymphopoietin (TSLP,Q969D9)

Comments Decoy receptor that binds IL-13 (IL13,P35225) as a monomer.

– – –

Subunits

Nomenclature Interleukin-2 receptor subunit α Interleukin-2 receptor subunit β Interleukin-2 receptor subunit γ Interleukin-4 receptor subunit α Interleukin-7 receptor subunit α

HGNC, UniProt IL2RA, P01589 IL2RB, P14784 IL2RG, P31785 IL4R, P24394 IL7R, P16871

Antibodies daclizumab (Binding) (pKd >8)[154], basiliximab (Binding)

– – dupilumab (Binding) (pIC50 11.1)[121]

–

Nomenclature Interleukin 9 receptor Interleukin-13 receptor subunit α1 Interleukin-15 receptor subunit α Interleukin 21 receptor Cytokine receptor-like factor 2

HGNC, UniProt IL9R, Q01113 IL13RA1, P78552 IL15RA, Q13261 IL21R, Q9HBE5 CRLF2, Q9HC73



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IL-3 receptor familyCatalytic receptors! Cytokine receptor family! IL-3 receptor familyOverview: The IL-3 receptor family signal through a receptor complex comprising of a ligand-specific α subunit and a common β chain (CSF2RB, P32927), which is associated with Jak2 and signalsprimarily through Stat5.

Nomenclature Interleukin-3 receptor Interleukin-5 receptor Granulocyte macrophage colony-stimulating factor receptor

Subunits Interleukin 3 receptor, α subunit(Ligand-binding subunit),Cytokine receptor common β subunit(Other subunit)

Interleukin 5 receptor, α subunit(Ligand-binding subunit),Cytokine receptor common β subunit(Other subunit)

GM-CSF receptor, α subunit (Ligand-binding subunit),Cytokine receptor common β subunit (Other subunit)

Endogenousagonists

IL-3 (IL3, P08700) IL-5 (IL5, P05113) G-CSF (CSF3, P09919), GM-CSF (CSF2, P04141)

Selectiveantagonists

– YM90709 [133] –

Subunits

Nomenclature Interleukin 3 receptor, α subunit Interleukin 5 receptor, α subunit GM-CSF receptor, α subunit Cytokine receptor common β subunit

HGNC, UniProt IL3RA, P26951 IL5RA, Q01344 CSF2RA, P15509 CSF2RB, P32927

Endogenous agonists IL-3 (IL3, P08700) IL-5 (IL5, P05113) GM-CSF (CSF2, P04141) –

Antibodies – benralizumab (Binding) (pKd 8.7) [93] mavrilimumab (Binding) (pIC50 9.9) [29] –

IL-6 receptor familyCatalytic receptors! Cytokine receptor family! IL-6 receptor familyOverview: The IL-6 receptor family signal through a ternary receptor complex consisting of the cognate receptor and either the IL-6 signal transducer gp130 (IL6ST, P40189) or the oncostatin M-specificreceptor, β subunit (OSMR, Q99650), which then activates the JAK/STAT, Ras/Raf/MAPK and PI 3-kinase/PKB signalling modules. Unusually amongst the cytokine receptors, the CNTF receptor is aglycerophosphatidylinositol-linked protein.



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Nomenclature Interleukin-6 receptor Interleukin-11 receptor Interleukin-31 receptor Ciliary neutrophic factor receptor

Subunits Interleukin-6 receptor, α subunit(Ligand-binding subunit),Interleukin-6 receptor, β subunit (Othersubunit)

Interleukin-11 receptor, α subunit(Ligand-binding subunit),Interleukin-6 receptor, β subunit (Othersubunit)

Interleukin-31 receptor, α subunit(Ligand-binding subunit),Oncostatin M-specific receptor, β subunit(Other subunit)

Leukemia inhibitory factor receptor (Othersubunit), Interleukin-6 receptor, β subunit,Ciliary neurotrophic factor receptor α subunit(Ligand-binding subunit)

Endogenousagonists

IL-6 (IL6, P05231) IL-11 (IL11, P20809) IL-31 (IL31, Q6EBC2) CRCF1/CLCF1 heterodimer (CLCF1 CRLF1,O75462 Q9UBD9),ciliary neurotrophic factor (CNTF, P26441)

Agonists – oprelvekin – –

Antibodies tocilizumab (Binding) (pKd 8.6) – – –

Nomenclature Leptin receptor Leukemia inhibitory factor receptor Oncostatin-M receptor Interleukin-27 receptor

HGNC, UniProt LEPR, P48357 – – –

Subunits – Leukemia inhibitory factor receptor(Ligand-binding subunit),Interleukin-6 receptor, β subunit (Othersubunit)

Interleukin-6 receptor, β subunit (Othersubunit),Oncostatin M-specific receptor, β subunit(Ligand-binding subunit)

Interleukin-6 receptor, β subunit(Other subunit),Interleukin 27 receptor, alpha(Ligand-binding subunit)

Endogenous agonists leptin (LEP, P41159) LIF (LIF, P15018), cardiotrophin-1 (CTF1,Q16619), oncostatin M (OSM, P13725)

oncostatin M (OSM, P13725) IL-27 (EBI3 IL27, Q14213Q8NEV9)

Subunits

Nomenclature Interleukin-6 receptor, α subunit Interleukin-6 receptor, β subunit Interleukin-11 receptor, α subunit Interleukin 27 receptor, alpha

HGNC, UniProt IL6R, P08887 IL6ST, P40189 IL11RA, Q14626 IL27RA, Q6UWB1

Antibodies sarilumab (Binding) (pKd10.6–11.1) [171]

– – –

Nomenclature Interleukin-31 receptor, α subunit Ciliary neurotrophic factor receptor α subunit Leukemia inhibitory factor receptor Oncostatin M-specific receptor, β subunit

HGNC, UniProt IL31RA, Q8NI17 CNTFR, P26992 LIFR, P42702 OSMR, Q99650



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tId=1714http://www.genenames.org/data/hgnc_data.php?hgnc_id=18969http://www.uniprot.org/uniprot/Q8NI17http://www.genenames.org/data/hgnc_data.php?hgnc_id=2170http://www.uniprot.org/uniprot/P26992http://www.genenames.org/data/hgnc_data.php?hgnc_id=6597http://www.uniprot.org/uniprot/P42702http://www.genenames.org/data/hgnc_data.php?hgnc_id=8507http://www.uniprot.org/uniprot/Q99650http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


IL-12 receptor familyCatalytic receptors! Cytokine receptor family! IL-12 receptor familyOverview: IL-12 receptors are a subfamily of the IL-6 receptor family. IL12RB1 is shared between receptors for IL-12 and IL-23; the functional agonist at IL-12 receptors is a heterodimer of IL-12A/IL-12B,while that for IL-23 receptors is a heterodimer of IL-12B/IL-23A.

Nomenclature Interleukin-12 receptor Interleukin-23 receptor Interleukin-12 receptor, β1subunit

Interleukin-12 receptor, β2subunit

Interleukin 23 receptor

HGNC, UniProt – – IL12RB1, P42701 IL12RB2, Q99665 IL23R, Q5VWK5

Subunits Interleukin-12 receptor, β2 subunit(Other subunit),Interleukin-12 receptor, β1 subunit(Ligand-binding subunit)

Interleukin 23 receptor (Ligand-bindingsubunit),Interleukin-12 receptor, β1 subunit(Ligand-binding subunit)

– – –

Endogenous agonists IL-12 (IL12A IL12B, P29459 P29460) IL-23 (IL12B IL23A, P29460) – – –

Prolactin receptor familyCatalytic receptors! Cytokine receptor family! Prolactin receptor familyOverview: Prolactin family receptors form homodimers in the presence of their respective ligands, associate exclusively with Jak2 and signal via Stat5.

Nomenclature Eythropoietin receptor Granulocyte colony-stimulatingfactor receptor

Growth hormone receptor Prolactin receptor Thrombopoietin receptor

HGNC, UniProt EPOR, P19235 CSF3R, Q99062 GHR, P10912 PRLR, P16471 MPL, P40238

Endogenous agonists erythropoietin (EPO, P01588)(Selective) (pIC50 11.1) [48]

G-CSF (CSF3, P09919) growth hormone 1 (GH1,P01241), growth hormone 2(GH2, P01242)

choriomammotropin (CSH1 CSH2,P01243),chorionic somatomammotropinhormone-like 1(CSHL1, Q14406), prolactin (PRL,P01236)

thrombopoietin (THPO, P40225)

Agonists peginesatide (pIC50 10.4) [48] pegfilgrastim – – romiplostim

Selective agonists – – – – eltrombopag (pEC50 7.4) [119]

Antagonists – – pegvisomant [180] – –

Searchable database: http://www.guidetopharmacology.org/index.jsp Prolactin receptor family 5985


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Interferon receptor familyCatalytic receptors! Cytokine receptor family! Interferon receptor familyOverview: The interferon receptor family includes receptors fortype I (α, β � and !) and type II (γ) interferons. There are at least13 different genes encoding IFN-α subunits in a cluster on human

chromosome 9p22: α1 (IFNA1, P01562), α2 (IFNA2, P01563), α4(IFNA4, P05014), α5 (IFNA5, P01569), α6 (IFNA6, P05013), α7(IFNA7, P01567), α8 (IFNA8, P32881), α10 (IFNA10, P01566), α13

(IFNA13, P01562), α14 (IFNA14, P01570), α16 (IFNA16, P05015),α17 (IFNA17, P01571) and α21 (IFNA21, P01568).

Nomenclature Interferon-α/β receptor Interferon-γ receptor

Subunits Interferon α/β receptor 2 (Other subunit), interferon α/β receptor 1 (Ligand-bindingsubunit)

Interferon γ receptor 2 (Other subunit), Interferon γ receptor 1 (Ligand-bindingsubunit)

Endogenousagonists

IFN-α1/13 (IFNA1 IFNA13, P01562), IFN-α10 (IFNA10, P01566), IFN-α14 (IFNA14,P01570), IFN-α16 (IFNA16, P05015), IFN-α17 (IFNA17, P01571), IFN-α2 (IFNA2,P01563), IFN-α21 (IFNA21, P01568), IFN-α4 (IFNA4, P05014), IFN-α5 (IFNA5,P01569), IFN-α6 (IFNA6, P05013), IFN-α7 (IFNA7, P01567), IFN-α8 (IFNA8, P32881),IFN-β (IFNB1, P01574), IFN-� (IFNK, Q9P0W0), IFN-! (IFNW1, P05000) IFN-γ (IFNG, P01579)

Selective agonists peginterferon alfa-2b [191] –

Subunits

Nomenclature interferon α/β receptor 1 Interferon α/β receptor 2 Interferon γ receptor 1 Interferon γ receptor 2

HGNC, UniProt IFNAR1, P17181 IFNAR2, P48551 IFNGR1, P15260 IFNGR2, P38484

Selective agonists peginterferon alfa-2b [191] – – –

Antibodies anifrolumab (Binding) (pKd >10) [21] – – –

Searchable database: http://www.guidetopharmacology.org/index.jsp Interferon receptor family 5986


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=310http://www.uniprot.org/uniprot/P01562http://www.uniprot.org/uniprot/P01563http://www.uniprot.org/uniprot/P05014http://www.uniprot.org/uniprot/P01569http://www.uniprot.org/uniprot/P05013http://www.uniprot.org/uniprot/P01567http://www.uniprot.org/uniprot/P32881http://www.uniprot.org/uniprot/P01566http://www.uniprot.org/uniprot/P01562http://www.uniprot.org/uniprot/P01570http://www.uniprot.org/uniprot/P05015http://www.uniprot.org/uniprot/P01571http://www.uniprot.org/uniprot/P01568http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1898http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1899http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1724http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1723http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1726http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1725http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4955http://www.genenames.org/data/hgnc_data.php?hgnc_id=5417http://www.genenames.org/data/hgnc_data.php?hgnc_id=5419http://www.uniprot.org/uniprot/P01562http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4956http://www.genenames.org/data/hgnc_data.php?hgnc_id=5418http://www.uniprot.org/uniprot/P01566http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4957http://www.genenames.org/data/hgnc_data.php?hgnc_id=5420http://www.uniprot.org/uniprot/P01570http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4958http://www.genenames.org/data/hgnc_data.php?hgnc_id=5421http://www.uniprot.org/uniprot/P05015http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4959http://www.genenames.org/data/hgnc_data.php?hgnc_id=5422http://www.uniprot.org/uniprot/P01571http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4960http://www.genenames.org/data/hgnc_data.php?hgnc_id=5423http://www.uniprot.org/uniprot/P01563http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4961http://www.genenames.org/data/hgnc_data.php?hgnc_id=5424http://www.uniprot.org/uniprot/P01568http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4962http://www.genenames.org/data/hgnc_data.php?hgnc_id=5425http://www.uniprot.org/uniprot/P05014http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4963http://www.genenames.org/data/hgnc_data.php?hgnc_id=5426http://www.uniprot.org/uniprot/P01569http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4964http://www.genenames.org/data/hgnc_data.php?hgnc_id=5427http://www.uniprot.org/uniprot/P05013http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4965http://www.genenames.org/data/hgnc_data.php?hgnc_id=5428http://www.uniprot.org/uniprot/P01567http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4966http://www.genenames.org/data/hgnc_data.php?hgnc_id=5429http://www.uniprot.org/uniprot/P32881http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4967http://www.genenames.org/data/hgnc_data.php?hgnc_id=5434http://www.uniprot.org/uniprot/P01574http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4969http://www.genenames.org/data/hgnc_data.php?hgnc_id=21714http://www.uniprot.org/uniprot/Q9P0W0http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4970http://www.genenames.org/data/hgnc_data.php?hgnc_id=5448http://www.uniprot.org/uniprot/P05000http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4968http://www.genenames.org/data/hgnc_data.php?hgnc_id=5438http://www.uniprot.org/uniprot/P01579http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7462http://www.ncbi.nlm.nih.gov/pubmed/10607680?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1723http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1724http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1725http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1726http://www.genenames.org/data/hgnc_data.php?hgnc_id=5432http://www.uniprot.org/uniprot/P17181http://www.genenames.org/data/hgnc_data.php?hgnc_id=5433http://www.uniprot.org/uniprot/P48551http://www.genenames.org/data/hgnc_data.php?hgnc_id=5439http://www.uniprot.org/uniprot/P15260http://www.genenames.org/data/hgnc_data.php?hgnc_id=5440http://www.uniprot.org/uniprot/P38484http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7462http://www.ncbi.nlm.nih.gov/pubmed/10607680?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8258http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


IL-10 receptor familyCatalytic receptors! Cytokine receptor family! IL-10 receptor familyOverview: The IL-10 family of receptors are heterodimeric combinations of family members: IL10RA/IL10RB responds to IL-10; IL20RA/IL20RB responds to IL-19, IL-20 and IL-24; IL22RA1/IL20RBresponds to IL-20 and IL-24; IL22RA1/IL10RB responds to IL-22; IL28RA/IL10RB responds to IL-28A, IL28B and IL-29.

Nomenclature Interleukin-10 receptor Interleukin-20 receptor Interleukin-22α1/20βheteromer

Interleukin-22α1/10βheteromer

Interleukin-22 receptor α2 Interferon-� receptor 1HGNC, UniProt – – – – IL22RA2, Q969J5 –

SubunitsInterleukin 10 receptor,α subunit(Ligand-binding subunit),Interleukin 10 receptor,β subunit(Other subunit)

Interleukin 20 receptor,β subunit(Other subunit),Interleukin 20 receptor,α subunit(Ligand-binding subunit)

Interleukin 22 receptor,α1 subunit(Ligand-binding subunit),Interleukin 20 receptor,β subunit(Ligand-binding subunit)

Interleukin 22 receptor,α1 subunit(Ligand-binding subunit),Interleukin 10 receptor,β subunit(Ligand-binding subunit)

–Interferon-� receptor subunit 1(Ligand-binding subunit),Interleukin 10 receptor,β subunit(Other subunit)

Endogenousagonists

IL-10 (IL10, P22301) IL-19 (IL19, Q9UHD0), IL-20(IL20, Q9NYY1), IL-24 (IL24,Q13007)

IL-20 (IL20, Q9NYY1), IL-24(IL24, Q13007)

IL-22 (IL22, Q9GZX6) – IFN-�1 (IFNL1, Q8IU54),IFN-�2 (IFNL2, Q8IZJ0),IFN-�3 (IFNL3, Q8IZI9)

Comments – – – – Soluble decoy receptor thatbinds IL-22 (IL22, Q9GZX6) asa monomer.

–

Subunits

Nomenclature Interleukin 10 receptor,α subunit

Interleukin 10 receptor,β subunit

Interleukin 20 receptor,α subunit

Interleukin 20 receptor,β subunit

Interleukin 22 receptor,α1 subunit

Interferon-�receptor subunit 1

HGNC, UniProt IL10RA, Q13651 IL10RB, Q08334 IL20RA, Q9UHF4 IL20RB, Q6UXL0 IL22RA1, Q8N6P7 IFNLR1, Q8IU57



http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=311http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1900http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1901http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1902http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1903http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1732http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1904http://www.genenames.org/data/hgnc_data.php?hgnc_id=14901http://www.uniprot.org/uniprot/Q969J5http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1727http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1728http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1730http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1729http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1731http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1730http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1731http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1728http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1733http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1728http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4975http://www.genenames.org/data/hgnc_data.php?hgnc_id=5962http://www.uniprot.org/uniprot/P22301http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4984http://www.genenames.org/data/hgnc_data.php?hgnc_id=5990http://www.uniprot.org/uniprot/Q9UHD0http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4986http://www.genenames.org/data/hgnc_data.php?hgnc_id=6002http://www.uniprot.org/uniprot/Q9NYY1http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4990http://www.genenames.org/data/hgnc_data.php?hgnc_id=11346http://www.uniprot.org/uniprot/Q13007http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4986http://www.genenames.org/data/hgnc_data.php?hgnc_id=6002http://www.uniprot.org/uniprot/Q9NYY1http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4990http://www.genenames.org/data/hgnc_data.php?hgnc_id=11346http://www.uniprot.org/uniprot/Q13007http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4988http://www.genenames.org/data/hgnc_data.php?hgnc_id=14900http://www.uniprot.org/uniprot/Q9GZX6http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4993http://www.genenames.org/data/hgnc_data.php?hgnc_id=18363http://www.uniprot.org/uniprot/Q8IU54http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4991http://www.genenames.org/data/hgnc_data.php?hgnc_id=18364http://www.uniprot.org/uniprot/Q8IZJ0http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4992http://www.genenames.org/data/hgnc_data.php?hgnc_id=18365http://www.uniprot.org/uniprot/Q8IZI9http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4988http://www.genenames.org/data/hgnc_data.php?hgnc_id=14900http://www.uniprot.org/uniprot/Q9GZX6http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1727http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1728http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1729http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1730http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1731http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1733http://www.genenames.org/data/hgnc_data.php?hgnc_id=5964http://www.uniprot.org/uniprot/Q13651http://www.genenames.org/data/hgnc_data.php?hgnc_id=5965http://www.uniprot.org/uniprot/Q08334http://www.genenames.org/data/hgnc_data.php?hgnc_id=6003http://www.uniprot.org/uniprot/Q9UHF4http://www.genenames.org/data/hgnc_data.php?hgnc_id=6004http://www.uniprot.org/uniprot/Q6UXL0http://www.genenames.org/data/hgnc_data.php?hgnc_id=13700http://www.uniprot.org/uniprot/Q8N6P7http://www.genenames.org/data/hgnc_data.php?hgnc_id=18584http://www.uniprot.org/uniprot/Q8IU57http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


Immunoglobulin-like family of IL-1 receptorsCatalytic receptors! Cytokine receptor family! Immunoglobulin-like family of IL-1 receptorsOverview: The immunoglobulin-like family of IL-1 receptors are heterodimeric receptors made up of a cognate receptor subunit and an IL-1 receptor accessory protein, IL1RAP (Q9NPH3, also known asC3orf13, IL-1RAcP, IL1R3). They are characterised by extracellular immunoglobulin-like domains and an intracellular Toll/Interleukin-1R (TIR) domain.

Nomenclature Interleukin-1 receptor, type I Interleukin-33 receptor Interleukin-36 receptor Interleukin-1 receptor, type II Interleukin-18 receptor

Subunits IL-1 receptor accessory protein

(Other subunit),Interleukin 1 receptor, type I(Ligand-binding subunit)

IL-1 receptor accessory protein

(Other subunit),Interleukin-1 receptor-like 1(Ligand-binding subunit)


(Other subunit),Interleukin-1 receptor-like 2(Ligand-binding subunit)


(Other subunit),Interleukin 1 receptor, type II(Ligand-binding subunit)


(Other subunit),Interleukin-18 1 (Ligand-binding subunit)

Inhibitors anakinra (pKd 7.8) [44] – – – –

Endogenousagonists

IL-1α (IL1A, P01583), IL-1β (IL1B,P01584)

IL-33 (IL33, O95760) IL-36α (IL36A, Q9UHA7), IL-36β(IL36B, Q9NZH7), IL-36γ (IL36G,Q9NZH8)

– IL-18 (IL18, Q14116), IL-37 (IL37,Q9NZH6)

Endogenousantagonists

IL-1 receptor antagonist (IL1RN,P18510)

– IL-36 receptor antagonist (IL36RN,Q9UBH0)

– –

Selectiveantagonists

AF12198 [3] – – – –

Comments – – IL-36 receptor antagonist (IL36RN,Q9UBH0) is a highly specificantagonist of the response toIL-36γ (IL36G, Q9NZH8).

Decoy receptor that binds IL-1α(IL1A, P01583), IL-1β (IL1B,P01584) andIL-1 receptor antagonist (IL1RN,P18510).

–

Subunits

Nomenclature Interleukin 1 receptor, type I Interleukin 1 receptor, type II Interleukin-1 receptor-like 1 Interleukin-1 receptor-like 2 Interleukin-18 1

HGNC, UniProt IL1R1, P14778 IL1R2, P27930 IL1RL1, Q01638 IL1RL2, Q9HB29 IL18R1, Q13478

Searchable database: http://www.guidetopharmacology.org/index.jsp Immunoglobulin-like family of IL-1 receptors 5988


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=312http://www.genenames.org/data/hgnc_data.php?hgnc_id=5995http://www.uniprot.org/uniprot/Q9NPH3http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1905http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1906http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1907http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2321http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1908http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1897http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1734http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1897http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1735http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1897http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1736http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1897http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2319http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2320http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1737http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6972http://www.ncbi.nlm.nih.gov/pubmed/1834644?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4973http://www.genenames.org/data/hgnc_data.php?hgnc_id=5991http://www.uniprot.org/uniprot/P01583http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4974http://www.genenames.org/data/hgnc_data.php?hgnc_id=5992http://www.uniprot.org/uniprot/P01584http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5880http://www.genenames.org/data/hgnc_data.php?hgnc_id=16028http://www.uniprot.org/uniprot/O95760http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5881http://www.genenames.org/data/hgnc_data.php?hgnc_id=15562http://www.uniprot.org/uniprot/Q9UHA7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5882http://www.genenames.org/data/hgnc_data.php?hgnc_id=15564http://www.uniprot.org/uniprot/Q9NZH7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5883http://www.genenames.org/data/hgnc_data.php?hgnc_id=15741http://www.uniprot.org/uniprot/Q9NZH8http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4983http://www.genenames.org/data/hgnc_data.php?hgnc_id=5986http://www.uniprot.org/uniprot/Q14116http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6149http://www.genenames.org/data/hgnc_data.php?hgnc_id=15563http://www.uniprot.org/uniprot/Q9NZH6http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5878http://www.genenames.org/data/hgnc_data.php?hgnc_id=6000http://www.uniprot.org/uniprot/P18510http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5879http://www.genenames.org/data/hgnc_data.php?hgnc_id=15561http://www.uniprot.org/uniprot/Q9UBH0http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4861http://www.ncbi.nlm.nih.gov/pubmed/8940020?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5879http://www.genenames.org/data/hgnc_data.php?hgnc_id=15561http://www.uniprot.org/uniprot/Q9UBH0http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5883http://www.genenames.org/data/hgnc_data.php?hgnc_id=15741http://www.uniprot.org/uniprot/Q9NZH8http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4973http://www.genenames.org/data/hgnc_data.php?hgnc_id=5991http://www.uniprot.org/uniprot/P01583http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4974http://www.genenames.org/data/hgnc_data.php?hgnc_id=5992http://www.uniprot.org/uniprot/P01584http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5878http://www.genenames.org/data/hgnc_data.php?hgnc_id=6000http://www.uniprot.org/uniprot/P18510http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1734http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2319http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1735http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1736http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1737http://www.genenames.org/data/hgnc_data.php?hgnc_id=5993http://www.uniprot.org/uniprot/P14778http://www.genenames.org/data/hgnc_data.php?hgnc_id=5994http://www.uniprot.org/uniprot/P27930http://www.genenames.org/data/hgnc_data.php?hgnc_id=5998http://www.uniprot.org/uniprot/Q01638http://www.genenames.org/data/hgnc_data.php?hgnc_id=5999http://www.uniprot.org/uniprot/Q9HB29http://www.genenames.org/data/hgnc_data.php?hgnc_id=5988http://www.uniprot.org/uniprot/Q13478http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


IL-17 receptor familyCatalytic receptors! Cytokine receptor family! IL-17 receptor familyOverview: The IL17 cytokine family consists of six ligands (IL-17A-F), which signal through five receptors (IL-17RA-E).

Nomenclature Interleukin-17 receptor Interleukin-25 receptor Interleukin-17C receptor

Subunits Interleukin 17 receptor A

(Ligand-binding subunit),interleukin 17 receptor C

(Other subunit)

Interleukin 17 receptor B

(Ligand-binding subunit),Interleukin 17 receptor A

(Other subunit)

Interleukin 17 receptor A

(Other subunit),Interleukin 17 receptor E

(Ligand-binding subunit)

Endogenous agonists IL-17A (IL17A, Q16552), IL-17A/IL-17F (IL17AIL17F, Q16552 Q96PD4), IL-17F (IL17F, Q96PD4)

IL-17B (IL17B, Q9UHF5), IL-25 (IL25, Q9H293) IL-17C (IL17C, Q9P0M4)

Subunits

Nomenclature Interleukin 17 receptor A Interleukin 17 receptor B interleukin 17 receptor C Interleukin-17 receptor D Interleukin 17 receptor E

HGNC, UniProt IL17RA, Q96F46 IL17RB, Q9NRM6 IL17RC, Q8NAC3 IL17RD, Q8NFM7 IL17RE, Q8NFR9

Antibodies brodalumab (Binding)(pKd 9.2) [179]

– – – –

Comments – – – The endogenous agonistfor this receptor isunknown.

–

Further Reading

Broughton SE et al. (2012) The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognitionto initiation of signaling. Immunol. Rev. 250: 277-302 [PMID:23046136]

Chang SH et al. (2011) Signaling of interleukin-17 family cytokines in immunity and inflammation.Cell. Signal. 23: 1069-75 [PMID:21130872]

George PM et al. (2012) Pharmacology and therapeutic potential of interferons. Pharmacol. Ther.135: 44-53 [PMID:22484806]

Gibbert K et al. (2013) IFN-α subtypes: distinct biological activities in anti-viral therapy. Br. J.Pharmacol. 168: 1048-58 [PMID:23072338]

Mackall CL et al. (2011) Harnessing the biology of IL-7 for therapeutic application. Nat. Rev. Im-munol. 11: 330-42 [PMID:21508983]

Mihara M et al. (2012) IL-6/IL-6 receptor system and its role in physiological and pathological con-

ditions. Clin. Sci. 122: 143-59 [PMID:22029668]

Miossec P et al. (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov11: 763-76 [PMID:23023676]

Murugaiyan G et al. (2013) IL-27 in tumor immunity and immunotherapy. Trends Mol Med 19:108-16 [PMID:23306374]

Palmer G et al. (2011) Interleukin-33 biology with potential insights into human diseases. Nat RevRheumatol 7: 321-9 [PMID:21519352]

Pappu R et al. (2011) The interleukin-17 cytokine family: critical players in host defence and in-flammatory diseases. Immunology 134: 8-16 [PMID:21726218]

Rincon M. (2012) Interleukin-6: from an inflammatory marker to a target for inflammatory diseases.Trends Immunol. 33: 571-7 [PMID:22883707]



http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=313http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2294http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2295http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2296http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1738http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1740http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1739http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1738http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1738http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1742http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4982http://www.genenames.org/data/hgnc_data.php?hgnc_id=5981http://www.uniprot.org/uniprot/Q16552http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5874http://www.genenames.org/data/hgnc_data.php?hgnc_id=5981http://www.genenames.org/data/hgnc_data.php?hgnc_id=16404http://www.uniprot.org/uniprot/Q16552http://www.uniprot.org/uniprot/Q96PD4http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5873http://www.genenames.org/data/hgnc_data.php?hgnc_id=16404http://www.uniprot.org/uniprot/Q96PD4http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5877http://www.genenames.org/data/hgnc_data.php?hgnc_id=5982http://www.uniprot.org/uniprot/Q9UHF5http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5876http://www.genenames.org/data/hgnc_data.php?hgnc_id=13765http://www.uniprot.org/uniprot/Q9H293http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5875http://www.genenames.org/data/hgnc_data.php?hgnc_id=5983http://www.uniprot.org/uniprot/Q9P0M4http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1738http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1739http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1740http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1741http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1742http://www.genenames.org/data/hgnc_data.php?hgnc_id=5985http://www.uniprot.org/uniprot/Q96F46http://www.genenames.org/data/hgnc_data.php?hgnc_id=18015http://www.uniprot.org/uniprot/Q9NRM6http://www.genenames.org/data/hgnc_data.php?hgnc_id=18358http://www.uniprot.org/uniprot/Q8NAC3http://www.genenames.org/data/hgnc_data.php?hgnc_id=17616http://www.uniprot.org/uniprot/Q8NFM7http://www.genenames.org/data/hgnc_data.php?hgnc_id=18439http://www.uniprot.org/uniprot/Q8NFR9http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7540http://www.ncbi.nlm.nih.gov/pubmed/23046136?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21130872?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22484806?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23072338?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21508983?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22029668?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23023676?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23306374?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21519352?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21726218?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22883707?dopt=AbstractPlushttp://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


Rubino SJ et al. (2012) Innate IL-17 and IL-22 responses to enteric bacterial pathogens. Trends Im-munol. 33: 112-8 [PMID:22342740]

Tanaka T et al. (2012) Therapeutic targeting of the interleukin-6 receptor. Annu. Rev. Pharmacol.Toxicol. 52: 199-219 [PMID:21910626]

Wojno ED et al. (2012) New directions in the basic and translational biology of interleukin-27.Trends Immunol. 33: 91-7 [PMID:22177689]

Zhu S et al. (2012) IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeuticpotential. Clin. Sci. 122: 487-511 [PMID:22324470]

GDNF receptor familyCatalytic receptors! GDNF receptor familyOverview: GDNF family receptors (provisional nomenclature) are extrinsic tyrosine kinase receptors. Ligand binding to the extracellular domain of the glycosylphosphatidylinositol-linked cell-surfacereceptors (tabulated below) activates a transmembrane tyrosine kinase enzyme, RET (see Receptor Tyrosine Kinases). The endogenous ligands are typically dimeric, linked through disulphide bridges: glialcell-derived neurotrophic factor GDNF (GDNF, P39905) (211 aa); neurturin (NRTN, Q99748) (197 aa); artemin (ARTN, Q5T4W7) (237 aa) and persephin (PSPN, O60542) (PSPN, 156 aa).

Nomenclature GDNF family receptor α1 GDNF family receptor α2 GDNF family receptor α3 GDNF family receptor α4

Common abreviation GFRα1 GFRα2 GFRα3 GFRα4

HGNC, UniProt GFRA1, P56159 GFRA2, O00451 GFRA3, O60609 GFRA4, Q9GZZ7

Potency order GDNF (GDNF, P39905) > neurturin (NRTN,Q99748) > artemin (ARTN, Q5T4W7) neurturin (NRTN, Q99748) > GDNF (GDNF, P39905) artemin (ARTN, Q5T4W7) persephin (PSPN,O60542)

Labelled ligands [125I]GDNF (rat) (pKd 10.2–11.5) [92, 182] – – –

Comments: Inhibitors of other receptor tyrosine kinases, such as semaxanib, which inhibits VEGF receptor function, may also inhibit Ret function [131]. Mutations of RET and GDNF genes may beinvolved in Hirschsprung’s disease, which is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction.

Further Reading

Allen SJ et al. (2013) GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharma-col. Ther. 138: 155-75 [PMID:23348013]

Carnicella S et al. (2009) GDNF–a potential target to treat addiction. Pharmacol. Ther. 122: 9-18[PMID:19136027]

Liu H et al. (2012) Role of glial cell line-derived neurotrophic factor in perineural invasion of pan-creatic cancer. Biochim. Biophys. Acta 1826: 112-20 [PMID:22503821]

Mickiewicz AL et al. (2011) GDNF family ligands: a potential future for Parkinson’s disease therapy.CNS Neurol Disord Drug Targets 10: 703-11 [PMID:21838676]

Pascual A et al. (2011) GDNF and protection of adult central catecholaminergic neurons. J. Mol.Endocrinol. 46: R83-92 [PMID:21357726]

Rangasamy SB et al. (2010) Neurotrophic factor therapy for Parkinson’s disease. Prog. Brain Res. 184:237-64 [PMID:20887879]

Searchable database: http://www.guidetopharmacology.org/index.jsp GDNF receptor family 5990


http://www.ncbi.nlm.nih.gov/pubmed/22342740?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21910626?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22177689?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22324470?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=314http://www.genenames.org/data/hgnc_data.php?hgnc_id=9967http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=304http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4940http://www.genenames.org/data/hgnc_data.php?hgnc_id=4232http://www.uniprot.org/uniprot/P39905http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5032http://www.genenames.org/data/hgnc_data.php?hgnc_id=8007http://www.uniprot.org/uniprot/Q99748http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4871http://www.genenames.org/data/hgnc_data.php?hgnc_id=727http://www.uniprot.org/uniprot/Q5T4W7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5045http://www.genenames.org/data/hgnc_data.php?hgnc_id=9579http://www.uniprot.org/uniprot/O60542http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1743http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1744http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1745http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1746http://www.genenames.org/data/hgnc_data.php?hgnc_id=4243http://www.uniprot.org/uniprot/P56159http://www.genenames.org/data/hgnc_data.php?hgnc_id=4244http://www.uniprot.org/uniprot/O00451http://www.genenames.org/data/hgnc_data.php?hgnc_id=4245http://www.uniprot.org/uniprot/O60609http://www.genenames.org/data/hgnc_data.php?hgnc_id=13821http://www.uniprot.org/uniprot/Q9GZZ7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4940http://www.genenames.org/data/hgnc_data.php?hgnc_id=4232http://www.uniprot.org/uniprot/P39905http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5032http://www.genenames.org/data/hgnc_data.php?hgnc_id=8007http://www.uniprot.org/uniprot/Q99748http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4871http://www.genenames.org/data/hgnc_data.php?hgnc_id=727http://www.uniprot.org/uniprot/Q5T4W7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5032http://www.genenames.org/data/hgnc_data.php?hgnc_id=8007http://www.uniprot.org/uniprot/Q99748http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4940http://www.genenames.org/data/hgnc_data.php?hgnc_id=4232http://www.uniprot.org/uniprot/P39905http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4871http://www.genenames.org/data/hgnc_data.php?hgnc_id=727http://www.uniprot.org/uniprot/Q5T4W7http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5045http://www.genenames.org/data/hgnc_data.php?hgnc_id=9579http://www.uniprot.org/uniprot/O60542http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4851http://www.ncbi.nlm.nih.gov/pubmed/9192898?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/8657309?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5056http://www.ncbi.nlm.nih.gov/pubmed/17032739?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23348013?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/19136027?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/22503821?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21838676?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/21357726?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/20887879?dopt=AbstractPlushttp://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


IntegrinsCatalytic receptors! IntegrinsOverview: Integrins are unusual signalling proteins that func-tion to signal both from the extracellular environment into thecell, but also from the cytoplasm to the external of the cell. Theintracellular signalling cascades associated with integrin activa-tion focus on protein kinase activities, such as focal adhesionkinase and Src. Based on this association between extracellularsignals and intracellular protein kinase activity, we have chosento include integrins in the ‘Catalytic receptors’ section of thedatabase until more stringent criteria from NC-IUPHAR allowsprecise definition of their classification.

Integrins are heterodimeric entities, composed of α and β sub-units, each 1TM proteins, which bind components of the extra-cellular matrix or counter-receptors expressed on other cells. Oneclass of integrin contains an inserted domain (I) in its α subunit,and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), thisI domain contains the ligand binding site. All β subunits possessa similar I-like domain, which has the capacity to bind ligand,often recognising the RGD motif. The presence of an α subunitI domain precludes ligand binding through the β subunit. Inte-grins provide a link between ligand and the actin cytoskeleton

(through typically short intracellular domains). Integrins bind

several divalent cations, including a Mg2+ ion in the I or I-like

domain that is essential for ligand binding. Other cation bind-

ing sites may regulate integrin activity or stabilise the 3D struc-

ture. Integrins regulate the activity of particular protein kinases,

including focal adhesion kinase and integrin-linked kinase. Cel-

lular activation regulates integrin ligand affinity via inside-out

signalling and ligand binding to integrins can regulate cellular

activity via outside-in signalling.

Nomenclature integrin α1β1 integrin α2β1 integrin αIIbβ3 integrin α4β1

Subunits

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide,antigen CD29 includes MDF2,MSK12),integrin, alpha 1 subunit

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide,antigen CD29 includes MDF2,MSK12),integrin, alpha 2 subunit(CD49B, alpha 2 subunitof VLA-2 receptor)

integrin, beta 3 subunit(platelet glycoprotein IIIa,antigen CD61),integrin, alpha IIb subunit(platelet glycoprotein IIb ofIIb/IIIa complex, antigen CD41)

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide,antigen CD29 includesMDF2, MSK12),integrin, alpha 4 subunit(antigen CD49D, alpha 4 subunitof VLA-4 receptor)

Ligands collagen, laminin collagen, laminin,thrombospondin

fibrinogen (FGA FGB FGG, P02671P02675 P02679), fibronectin(FN1, P02751),von Willebrand factor (VWF,P04275), vitronectin (VTN,P04004), thrombospondin

fibronectin (FN1, P02751),vascular cell adhesion protein 1(VCAM1, P19320), osteopontin(SPP1, P10451), thrombospondin

Inhibitors obtustatin (pIC50 9.1) [118] TCI15 (pIC50 7.9) [128] G4120 [124], GR 144053,eptifibatide, tirofiban

BIO1211 (pIC50 8.3–9) [108],TCS2314

Antibodies – – abciximab (Binding) [31] natalizumab (Inhibition) [1]

Comments – – – LDV-FITC is used as a probe at thisreceptor.

Searchable database: http://www.guidetopharmacology.org/index.jsp Integrins 5991


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=760http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2577http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2578http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2579http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2580http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2455http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2437http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2455http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2440http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2457http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2441http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2455http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2443http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6749http://www.genenames.org/data/hgnc_data.php?hgnc_id=3661http://www.genenames.org/data/hgnc_data.php?hgnc_id=3662http://www.genenames.org/data/hgnc_data.php?hgnc_id=3694http://www.uniprot.org/uniprot/P02671http://www.uniprot.org/uniprot/P02675http://www.uniprot.org/uniprot/P02679http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6754http://www.genenames.org/data/hgnc_data.php?hgnc_id=3778http://www.uniprot.org/uniprot/P02751http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6755http://www.genenames.org/data/hgnc_data.php?hgnc_id=12726http://www.uniprot.org/uniprot/P04275http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6746http://www.genenames.org/data/hgnc_data.php?hgnc_id=12724http://www.uniprot.org/uniprot/P04004http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6754http://www.genenames.org/data/hgnc_data.php?hgnc_id=3778http://www.uniprot.org/uniprot/P02751http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6758http://www.genenames.org/data/hgnc_data.php?hgnc_id=12663http://www.uniprot.org/uniprot/P19320http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6753http://www.genenames.org/data/hgnc_data.php?hgnc_id=11255http://www.uniprot.org/uniprot/P10451http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6581http://www.ncbi.nlm.nih.gov/pubmed/12727812?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6582http://www.ncbi.nlm.nih.gov/pubmed/19141632?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6588http://www.ncbi.nlm.nih.gov/pubmed/7955174?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6587http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6585http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6586http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6589http://www.ncbi.nlm.nih.gov/pubmed/10072689?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6590http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6584http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6591http://www.ncbi.nlm.nih.gov/pubmed/15293871?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6759http://www.guidetopharmacology.org/index.jsphttp://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full


Nomenclature integrin α4β7 integrin α5β1 integrin α6β1 integrin α10β1

Subunits

integrin, alpha 4 subunit(antigen CD49D, alpha 4 subunitofVLA-4 receptor),integrin, beta 7 subunit

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide, antigen CD29includes MDF2, MSK12),integrin, alpha 5 subunit(fibronectin receptor, alphapolypeptide)

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide, antigen CD29includesMDF2, MSK12),integrin, alpha 6 subunit

integrin, beta 1 subunit(fibronectin receptor, betapolypeptide, antigen CD29includes MDF2, MSK12),integrin, alpha 10 subunit

Ligands – fibronectin (FN1, P02751) laminin collagen

Antibodies vedolizumab (Antagonist) (pIC508.3) [151]

– – –

Nomenclature integrin α11β1 integrin αEβ7 integrin αLβ2 integrin αVβ3

Subunits

integrin, beta 1 subunit(fibronectin receptor, beta polypeptide,antigen CD29includes MDF2, MSK12),integrin, alpha 11 subunit

integrin, alpha E subunit(antigen CD103, human mucosallymphocyteantigen 1; alpha polypeptide),integrin, beta 7 subunit

integrin, beta 2 subunit(complement component 3 receptor 3and 4 subunit),integrin, alpha L subunit(antigen CD11A (p180), lymphocytefunction-associatedantigen 1; alpha polypeptide)

integrin, beta 3 subunit(platelet glycoprotein IIIa,antigen CD61),integrin, alpha V subunit

Ligands collagen E-cadherin ICAM-1 (ICAM1, P05362), ICAM-2 (ICAM2,P13598)

vitronectin (VTN, P04004), fibronectin(FN1, P02751), fibrinogen (FGA FGBFGG, P02671 P02675 P02679),osteopontin (SPP1, P10451),von Willebrand factor (VWF, P04275),thrombospondin, tenascin

Inhibitors – – A286982 (pIC50 7.4–7.5) [110] echistatin (pIC50 11.7) [101], P11(pIC50 11.6) [101], cilengitide (pIC508.5) [61]

Antibodies – – – etaracizumab (Binding) (pKd 6.3) [201]

Comments: Integrin ligands

Collagen is the most abundant protein in metazoa, rich inglycine and proline residues, made up of cross-linked triple heli-cal structures, generated primarily by fibroblasts. Extensive post-translational processing is conducted by prolyl and lysyl hydrox-

ylases, as well as transglutaminases. Over 40 genes for collagen-

α subunits have been identified in the human genome. The

collagen-binding integrins α1β1, α2β1, α10β1 and α11β1 recog-

nise a range of triple-helical peptidemotifs including GFOGER (O

= hydroxyproline), a synthetic peptide derived from the primary

sequence of collagen I (COL1A1 (COL1A1, P02452)) and collagenII (COL2A1 (COL2A1, P02458)).

Laminin is an extracellular glycoprotein composed of α, β andγ chains, for which five, four and three genes, respectively, areidentified in the human genome. It binds to α1β1, α2β1, α3,β1,

Searchable database: http://www.guidetopharmacology.org/index.jsp Integrins 5992

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