ITGB1BP1
Description
The ITGB1BP1 (integrin subunit beta 1 binding protein 1) is a protein-coding gene located on chromosome 2.
Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ITGB1BP1 gene. 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.
== Interactions == ITGB1BP1 has been shown to interact with KRIT1, LRP2, CD29 and LRP1.
ITGB1BP1, also known as Integrin cytoplasmic domain-associated protein 1, is a key regulator of the integrin-mediated cell-matrix interaction signaling pathway. It binds to the ITGB1 cytoplasmic tail, preventing activation of integrin alpha-5/beta-1 (ITGA5/ITGB1) by talin or FERMT1. ITGB1BP1 plays a role in cell proliferation, differentiation, spreading, adhesion, and migration, particularly in the context of mineralization, bone development, and angiogenesis. It stimulates cellular proliferation in a fibronectin-dependent manner and regulates the dynamics of beta-1 integrin-containing focal adhesion (FA) sites by controlling their assembly rate during cell adhesion. ITGB1BP1 directly competes with talin TLN1, inhibiting beta-1 integrin clustering within FAs, which stimulates osteoblast spreading and migration in a fibronectin- and/or collagen-dependent manner. Acting as a guanine nucleotide dissociation inhibitor (GDI), it regulates Rho family GTPases during integrin-mediated cell matrix adhesion, reducing the active GTP-bound form of CDC42 and RAC1 GTPases upon cell adhesion to fibronectin. ITGB1BP1 stimulates the release of active CDC42 from membranes, maintaining it in an inactive cytoplasmic pool. It also participates in the translocation of Rho-associated protein kinase ROCK1 to membrane ruffles at cell leading edges, leading to increased myoblast cell migration on laminin. ITGB1BP1 plays a role in bone mineralization at a late stage of osteoblast differentiation, modulating the dynamic formation of focal adhesions into fibrillar adhesions, which are adhesive structures responsible for fibronectin deposition and fibrillogenesis. Additionally, it plays a role in blood vessel development, acting as a negative regulator of angiogenesis by attenuating endothelial cell proliferation, migration, lumen formation, and sprouting angiogenesis. This is achieved by promoting AKT phosphorylation and inhibiting ERK1/2 phosphorylation through activation of the Notch signaling pathway. ITGB1BP1 also promotes transcriptional activity of the MYC promoter.
ITGB1BP1 is also known as ICAP-1A, ICAP-1B, ICAP-1alpha, ICAP1, ICAP1A, ICAP1B.
Associated Diseases
- craniometadiaphyseal dysplasia, wormian bone type
- progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome
- pseudoachondroplasia
- Achondroplasia
- spondyloepiphyseal dysplasia tarda
- progressive pseudorheumatoid arthropathy of childhood
- metatropic dysplasia
- spondylometaphyseal dysplasia, Kozlowski type
- chondrodysplasia with joint dislocations, gPAPP type
- Eiken syndrome
- brachydactyly type B1
- cerebral cavernous malformation
- hip dysplasia, Beukes type
- brachyolmia type 1, Hobaek type
- fibrochondrogenesis 1
- osteogenesis imperfecta type 5
- rhizomelic syndrome, Urbach type
