InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ITGB1BP1

Summary

InnateDB Protein

IDBP-27506.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ITGB1BP1

Protein Name

integrin beta 1 binding protein 1

Synonyms

ICAP-1A; ICAP-1alpha; ICAP-1B; ICAP1; ICAP1A; ICAP1B;

Species

Homo sapiens

Ensembl Protein

ENSP00000238091

InnateDB Gene

IDBG-27498 (ITGB1BP1)

Protein Structure

UniProt Annotation

Function

Key regulator of the integrin-mediated cell-matrix interaction signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. Plays a role in cell proliferation, differentiation, spreading, adhesion and migration in the context of mineralization and bone development and angiogenesis. Stimulates cellular proliferation in a fibronectin- dependent manner. Involved in the regulation of beta-1 integrin- containing focal adhesion (FA) site dynamics by controlling its assembly rate during cell adhesion; inhibits beta-1 integrin clustering within FA by directly competing with talin TLN1, and hence stimulates osteoblast spreading and migration in a fibronectin-and/or collagen-dependent manner. Acts as a guanine nucleotide dissociation inhibitor (GDI) by regulating Rho family GTPases during integrin-mediated cell matrix adhesion; reduces the level of active GTP-bound form of both CDC42 and RAC1 GTPases upon cell adhesion to fibronectin. Stimulates the release of active CDC42 from the membranes to maintain it in an inactive cytoplasmic pool. Participates in the translocation of the Rho-associated protein kinase ROCK1 to membrane ruffles at cell leading edges of the cell membrane, leading to an increase of myoblast cell migration on laminin. Plays a role in bone mineralization at a late stage of osteoblast differentiation; modulates the dynamic formation of focal adhesions into fibrillar adhesions, which are adhesive structures responsible for fibronectin deposition and fibrillogenesis. Plays a role in blood vessel development; acts as a negative regulator of angiogenesis by attenuating endothelial cell proliferation and migration, lumen formation and sprouting angiogenesis by promoting AKT phosphorylation and inhibiting ERK1/2 phosphorylation through activation of the Notch signaling pathway. Promotes transcriptional activity of the MYC promoter. {ECO:0000269PubMed:11741838, ECO:0000269PubMed:11807099, ECO:0000269PubMed:11919189, ECO:0000269PubMed:12473654, ECO:0000269PubMed:15703214, ECO:0000269PubMed:17916086, ECO:0000269PubMed:20616313, ECO:0000269PubMed:21768292, ECO:0000269Ref.18}.

Subcellular Localization

Nucleus. Cytoplasm. Cytoplasm, cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}. Cell projection, lamellipodium. Cell projection, ruffle. Note=Nucleocytoplasmic shuttling protein; shuttles between nucleus and cytoplasm in a integrin-dependent manner; probably sequestered in the cytosol by ITGB1. Its localization is dependent on the stage of cell spreading on fibronectin; cytoplasmic in case of round cells, corresponding to the initial step of cell spreading, or nuclear in case of well spread cells. Colocalizes with ROCK1 and NME2 at beta-1 integrin engagement sites. Together with ITGB1 and NME2 is recruited to beta-1 integrin-rich peripheral ruffles and lamellipodia during initial cell spreading on fibronectin and/or collagen.

Disease Associations

Tissue Specificity

Expressed in endothelial cells and fibroblasts (at protein level). Ubiquitously expressed. Expressed in intestine, colon, testis, ovary, thymus, spleen and prostate. {ECO:0000269PubMed:9281591, ECO:0000269PubMed:9867804}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 16 experimentally validated interaction(s) in this database.

Experimentally validated
Total	16 [view]
Protein-Protein	16 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005092	GDP-dissociation inhibitor activity
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0008565	protein transporter activity
GO:0032403	protein complex binding

Biological Process

GO:0002043	blood vessel endothelial cell proliferation involved in sprouting angiogenesis
GO:0006351	transcription, DNA-templated
GO:0006469	negative regulation of protein kinase activity
GO:0006933	negative regulation of cell adhesion involved in substrate-bound cell migration
GO:0007160	cell-matrix adhesion
GO:0007219	Notch signaling pathway
GO:0007229	integrin-mediated signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0010595	positive regulation of endothelial cell migration
GO:0010764	negative regulation of fibroblast migration
GO:0015031	protein transport
GO:0016477	cell migration
GO:0030154	cell differentiation
GO:0031214	biomineral tissue development
GO:0032091	negative regulation of protein binding
GO:0032148	activation of protein kinase B activity
GO:0033622	integrin activation
GO:0033628	regulation of cell adhesion mediated by integrin
GO:0035148	tube formation
GO:0035556	intracellular signal transduction
GO:0035924	cellular response to vascular endothelial growth factor stimulus
GO:0043088	regulation of Cdc42 GTPase activity
GO:0043113	receptor clustering
GO:0044344	cellular response to fibroblast growth factor stimulus
GO:0045747	positive regulation of Notch signaling pathway
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0050880	regulation of blood vessel size
GO:0051451	myoblast migration
GO:0051496	positive regulation of stress fiber assembly
GO:0051781	positive regulation of cell division
GO:0051895	negative regulation of focal adhesion assembly
GO:0051897	positive regulation of protein kinase B signaling
GO:0070373	negative regulation of ERK1 and ERK2 cascade
GO:0090051	negative regulation of cell migration involved in sprouting angiogenesis
GO:0090314	positive regulation of protein targeting to membrane
GO:0090315	negative regulation of protein targeting to membrane
GO:1900025	negative regulation of substrate adhesion-dependent cell spreading
GO:2001044	regulation of integrin-mediated signaling pathway

Cellular Component

GO:0001726	ruffle
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0030027	lamellipodium
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome
GO:0071944	cell periphery