Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ITGAV (P06756) - Overview - Molecular Target Synopsis

Protein


ITGAV, Integrin alpha-V
UniProt P06756

Also Known as ITAV_HUMAN, ITGAV, MSK8, VNRA, VTNR

The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 and ITGAV:ITGB6 act as a receptor for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447)., (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C., (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1., (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8., (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1., (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1., (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus., (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-V (ITGAV) associates with either beta-1 (ITGB1), beta-3 (ITGB3), beta-5 (ITGB5), beta-6 (ITGB6) or beta-8 (ITGB8). Interacts with CIB1 (PubMed:24011356). Interacts with RAB25 (PubMed:17925226). Integrins ITGAV:ITGB3 and ITGAV:ITGB5 interact with FBLN5 (via N-terminus) (By similarity). ITGAV:ITGB3 and ITGAV:ITGB5 interact with CCN3 (PubMed:12695522). ITGAV:ITGB3 interacts with ADGRA2 (PubMed:16982628). ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (PubMed:28302677). ITGAV:ITGB3 interacts with IL1B (PubMed:29030430). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1 (PubMed:23125415). ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3 (PubMed:20682778). ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1 (PubMed:18441324). ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (PubMed:19578119). ITGAV:ITGB3 interacts with IGF2 (PubMed:28873464). ITGAV:ITGB3 and ITGAV:ITGB6 interact with FBN1 (PubMed:12807887, PubMed:17158881). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (PubMed:27993971). ITGAV:ITGB6 interacts with TGFB1 (PubMed:22278742, PubMed:28117447).

6DJP
INTEGRIN ALPHA-V BETA-8 IN COMPLEX WITH THE FABS 8B8 AND 68
RCSB/PDB
Inspect Structure
See all 3D Structures for ITGAV

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project ITGAV has gain in 5 cell-lines, loss in 4 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H522, OVCAR_4, RXF_393

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SNU-484, NCI-H1581, COV318

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, NHLF, BJ

(see details)

3D Structures


For ITGAV there are:
23 structures (26 chains) solved
19 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ITGAV has been screened with 1903 compounds (3321 bioactivities), 1196 compounds have bioactivities that show binding affinity of <= 500nM (1919 bioactivities). (see details)