ITGB1BP1

The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domain. The interaction between this protein and beta1 integrin is highly specific. Two isoforms of this protein are derived from alternatively spliced transcripts. The shorter form of this protein does not interact with the beta1 integrin cytoplasmic domain. The longer form is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction, suggesting an important role of this protein during integrin-dependent cell adhesion. [provided by RefSeq]

integrin beta 1 binding protein 1

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.

Activation of protein kinase B activityManual Assertion Based On ExperimentIDA:UniProtKB
Biomineral tissue developmentIEA:UniProtKB-KW
Blood vessel diameter maintenanceManual Assertion Based On ExperimentIDA:UniProtKB
Blood vessel endothelial cell proliferation involved in sprouting angiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Cell differentiationIEA:UniProtKB-KW
Cell migrationManual Assertion Based On ExperimentTAS:HGNC-UCL
Cell-matrix adhesionManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to fibroblast growth factor stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to vascular endothelial growth factor stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Integrin activationManual Assertion Based On ExperimentIDA:ComplexPortal
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Myoblast migrationISS:UniProtKB
Negative regulation of cell adhesion involved in substrate-bound cell migrationISS:UniProtKB
Negative regulation of cell migration involved in sprouting angiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of fibroblast migrationISS:UniProtKB
Negative regulation of focal adhesion assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein bindingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein targeting to membraneManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIDA:UniProtKB
Notch signaling pathwayIEA:UniProtKB-KW
Positive regulation of cell divisionIEA:UniProtKB-KW
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of focal adhesion assemblyIEA:Ensembl
Positive regulation of Notch signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein kinase B signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of protein targeting to membraneISS:UniProtKB
Positive regulation of stress fiber assemblyISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Protein localization to plasma membraneManual Assertion Based On ExperimentIDA:GO_Central
Receptor clusteringISS:UniProtKB
Regulation of cell adhesion mediated by integrinISS:UniProtKB
Regulation of GTPase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of integrin-mediated signaling pathwayISS:UniProtKB
Tube formationManual Assertion Based On ExperimentIDA:UniProtKB

Nucleus; Cytoplasm; Cytoplasm, cytoskeleton; Cell membrane; Cell projection, lamellipodium; Cell projection, ruffle. 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.

Extracellular: 21-728
Helical: 729-751
Cytoplasmic: 752-798

Phosphorylation at Thr-38 seems to enhance integrin alpha5beta1-mediated cell adhesion. The degree of phosphorylation is regulated by integrin-dependent cell-matrix interaction.