Target Information

Target General Infomation
Target ID
T97587
Former ID
TTDS00445
Target Name
Integrin alpha-4
Gene Name
ITGA4
Synonyms
CD49d; Integrin alpha 4 beta 1; Integrin alpha-IV; VLA-4; Very late antigen 4; CD49 antigenlike family member D; CD49d; Integrin alpha4; Integrin alphaIV; VLA4 subunit alpha; ITGA4
Target Type
Successful
Disease Autoimmune diabetes [ICD10: E08-E13]
Asthma [ICD10: J45]
Crohn's disease; Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Multiple scierosis [ICD9: 340; ICD10: G35]
Ulcerative colitis [ICD9: 556; ICD10: K51]
Ulcerative colitis; Crohn's disease [ICD9: 555, 556, 556.9; ICD10: K50, K50-K52, K51]
Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha- 4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha- 4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypicaggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.
BioChemical Class
Integrin
Target Validation
T97587
UniProt ID
P13612
Sequence
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHS
HGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLE
ERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI
APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLD
KQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGK
KLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG
SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEG
LQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVN
RTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT
SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQ
PILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLN
VSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH
LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHG
FVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLF
NILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF
LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVA
HVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRD
SWSYINSKSNDD
Structure
3V4P; 3V4V; 4HKC
Drugs and Mode of Action
Drug(s) Antegren Drug Info Approved Multiple scierosis [527466]
Vedolizmab Drug Info Approved Ulcerative colitis; Crohn's disease [551871]
BIO-1211 Drug Info Phase 2 Asthma [541708]
GSK683699 Drug Info Phase 2 Crohn's disease; Inflammatory bowel disease [536371]
ELND-002 Drug Info Phase 1 Autoimmune diabetes [523401]
ELND-004 Drug Info Phase 1 Autoimmune diabetes [548359]
Antagonist ASP-2002 Drug Info [550392]
BIO-1211 Drug Info [535024]
CT301 Drug Info [535621]
ELND-002 Drug Info [526636]
Vedolizmab Drug Info [551717]
Inhibitor ELND-004 Drug Info [526636]
Binder GSK683699 Drug Info [536371]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway PI3K-Akt signaling pathway
Focal adhesion
ECM-receptor interaction
Cell adhesion molecules (CAMs)
Hematopoietic cell lineage
Leukocyte transendothelial migration
Intestinal immune network for IgA production
Regulation of actin cytoskeleton
Leishmaniasis
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Dilated cardiomyopathy
PANTHER Pathway Integrin signalling pathway
Pathway Interaction Database Beta1 integrin cell surface interactions
Integrin family cell surface interactions
Arf6 trafficking events
CXCR4-mediated signaling events
Plexin-D1 Signaling
a4b7 Integrin signaling
Beta5 beta6 beta7 and beta8 integrin cell surface interactions
VEGFR3 signaling in lymphatic endothelium
Alpha4 beta1 integrin signaling events
Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
Integrin cell surface interactions
WikiPathways Focal Adhesion
Arrhythmogenic Right Ventricular Cardiomyopathy
Integrin-mediated Cell Adhesion
Integrin cell surface interactions
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
References
Ref 523401ClinicalTrials.gov (NCT01318421) A Study of ELND002 in Patients With Relapsing Forms of Multiple Sclerosis. U.S. National Institutes of Health.
Ref 5274662004 approvals: the demise of the blockbuster. Nat Rev Drug Discov. 2005 Feb;4(2):93-4.
Ref 536371Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.
Ref 541708(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6589).
Ref 548359Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024932)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 526636Paxillin binding to the alpha 4 integrin subunit stimulates LFA-1 (integrin alpha L beta 2)-dependent T cell migration by augmenting the activation of focal adhesion kinase/proline-rich tyrosine kinase-2. J Immunol. 2003 Jun 15;170(12):5912-8.
Ref 535024A small-molecule, tight-binding inhibitor of the integrin alpha(4)beta(1) blocks antigen-induced airway responses and inflammation in experimental asthma in sheep. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):603-11.
Ref 535621Prolonged reversal of chronic experimental allergic encephalomyelitis using a small molecule inhibitor of alpha4 integrin. J Neuroimmunol. 2002 Oct;131(1-2):147-59.
Ref 536371Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.
Ref 538125Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents. Curr Opin Chem Biol. 1998 Aug;2(4):453-7.
Ref 550392Asphelia to Present at C21 BioVentures Conference in Napa, CA. 10th Annual C21 BioVentures. May 15, 2008.
Ref 551717Clinical pipeline report, company report or official report of Takeda (2009).

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