Target Information

Target General Infomation
Target ID
T78892
Former ID
TTDR01371
Target Name
mRNA of integrin alpha-4
Gene Name
ITGA4
Synonyms
CD49 antigenlike family member D (mRNA); CD49d (mRNA); ITGA4 (mRNA); Integrin alpha4 (mRNA); Integrin alphaIV (mRNA); VLA4 subunit alpha (mRNA); ITGA4
Target Type
Clinical Trial
Disease Multiple scierosis [ICD9: 340; ICD10: G35]
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 homotypic aggregation 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
T78892
UniProt ID
P13612
Sequence
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHS
HGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLE
ERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI
APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLD
KQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGK
KLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG
SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEG
LQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVN
RTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT
SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQ
PILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLN
VSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH
LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHG
FVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLF
NILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF
LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVA
HVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRD
SWSYINSKSNDD
Drugs and Mode of Action
Drug(s) ATL1102 Drug Info Phase 2 Multiple scierosis [551049]
Modulator ATL1102 Drug Info
Inhibitor MK-0668 Drug Info [530343]
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 551049Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
Ref 530343Bioorg Med Chem Lett. 2009 Oct 1;19(19):5803-6. Epub 2009 Jul 28.Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3',5'-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist.
Ref 549636US patent application no. 6,258,790, Antisense modulation of integrin .alpha.4 expression.

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