Target General Infomation
Target ID
T14065
Former ID
TTDC00031
Target Name
Integrin beta-7
Gene Name
ITGB7
Synonyms
Gut homing receptor beta subunit; ITGB7
Target Type
Successful
Disease Crohn's disease [ICD9: 555; ICD10: K50]
Ulcerative colitis [ICD9: 556; ICD10: K51]
Ulcerative colitis; Crohn's disease [ICD9: 555, 556, 556.9; ICD10: K50, K50-K52, K51]
Function
Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, an extracellular matrix component. It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin. Interactions involves the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin. Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Interaction would involve a tripeptide L-D-I in HIV-1 gp120. Integrin alpha-E/beta-7 (HML-1) is a receptor for E-cadherin.
BioChemical Class
Integrin
Target Validation
T14065
UniProt ID
Sequence
MVALPMVLVLLLVLSRGESELDAKIPSTGDATEWRNPHLSMLGSCQPAPSCQKCILSHPS
CAWCKQLNFTASGEAEARRCARREELLARGCPLEELEEPRGQQEVLQDQPLSQGARGEGA
TQLAPQRVRVTLRPGEPQQLQVRFLRAEGYPVDLYYLMDLSYSMKDDLERVRQLGHALLV
RLQEVTHSVRIGFGSFVDKTVLPFVSTVPSKLRHPCPTRLERCQSPFSFHHVLSLTGDAQ
AFEREVGRQSVSGNLDSPEGGFDAILQAALCQEQIGWRNVSRLLVFTSDDTFHTAGDGKL
GGIFMPSDGHCHLDSNGLYSRSTEFDYPSVGQVAQALSAANIQPIFAVTSAALPVYQELS
KLIPKSAVGELSEDSSNVVQLIMDAYNSLSSTVTLEHSSLPPGVHISYESQCEGPEKREG
KAEDRGQCNHVRINQTVTFWVSLQATHCLPEPHLLRLRALGFSEELIVELHTLCDCNCSD
TQPQAPHCSDGQGHLQCGVCSCAPGRLGRLCECSVAELSSPDLESGCRAPNGTGPLCSGK
GHCQCGRCSCSGQSSGHLCECDDASCERHEGILCGGFGRCQCGVCHCHANRTGRACECSG
DMDSCISPEGGLCSGHGRCKCNRCQCLDGYYGALCDQCPGCKTPCERHRDCAECGAFRTG
PLATNCSTACAHTNVTLALAPILDDGWCKERTLDNQLFFFLVEDDARGTVVLRVRPQEKG
ADHTQAIVLGCVGGIVAVGLGLVLAYRLSVEIYDRREYSRFEKEQQQLNWKQDSNPLYKS
AITTTINPRFQEADSPTL
Structure
3V4P; 3V4V; 4HKC; 2BRQ; 3V4P; 3V4V
Drugs and Mode of Action
Drug(s) Vedolizmab Drug Info Approved Ulcerative colitis; Crohn's disease [551871]
Rhumab Beta7 Drug Info Phase 3 Ulcerative colitis [548506]
AMG-181 Drug Info Phase 2 Crohn's disease [524078]
Antagonist Vedolizmab Drug Info [551717]
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)
Intestinal immune network for IgA production
Regulation of actin cytoskeleton
Transcriptional misregulation in cancer
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Dilated cardiomyopathy
NetPath Pathway IL2 Signaling Pathway
Wnt Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Integrin signalling pathway
Pathway Interaction Database Integrin family cell surface interactions
AlphaE beta7 integrin cell surface interactions
E-cadherin signaling in the nascent adherens junction
a4b7 Integrin signaling
Beta5 beta6 beta7 and beta8 integrin cell surface interactions
Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
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
References
Ref 524078ClinicalTrials.gov (NCT01696396) AMG 181 in Subjects With Moderate to Severe Crohn's Disease. U.S. National Institutes of Health.
Ref 548506Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026082)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 531945A randomised phase I study of etrolizumab (rhuMAb beta7) in moderate to severe ulcerative colitis. Gut. 2013 Aug;62(8):1122-30.
Ref 532239Pharmacology of AMG 181, a human anti-alpha4 beta7 antibody that specifically alters trafficking of gut-homing T cells. Br J Pharmacol. 2013 May;169(1):51-68.
Ref 550797Clinical pipeline report, company report or official report of Genentech (2009).
Ref 551717Clinical pipeline report, company report or official report of Takeda (2009).

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