High impact information on ITGB1BP1

• Two isoforms of ICAP-1, a 200-amino acid protein (ICAP-1alpha) and a shorter 150-amino acid protein (ICAP-1beta), derived from alternatively spliced mRNA, are expressed in most cells [1].
• We report identification of a novel protein, ICAP-1 (integrin cytoplasmic domain- associated protein-1), which binds to the 1 integrin cytoplasmic domain [1].
• Mutational studies reveal that Asn and Tyr of the NPXY motif and a Val residue located NH2-terminal to this motif are critical for the ICAP-1 binding [1].
• The regulation of ICAP-1alpha phosphorylation by the cell-matrix interaction suggests an important role of ICAP-1 during integrin-dependent cell adhesion [1].
• CCM2 and ICAP1 bound to CCM1 via their respective PTB domains differentially influence the subcellular localization of CCM1 [2].

Biological context of ITGB1BP1

• Icap1 binds to a NPXY motif in the cytoplasmic domain of beta1 integrin and participates in beta1-mediated cell adhesion and migration [3].
• Like beta1 integrin, krit1 interacts with the 200 amino acid isoform of icap1 (icap1alpha), but not a 150 amino acid form that results from alternative splicing (icap1beta) [3].
• From parallel screens of human fetal brain and HeLa cDNA libraries, we obtained multiple independent isolates of human integrin cytoplasmic domain-associated protein-1 (ICAP-1) as interacting clones [4].
• Nuclear translocation of integrin cytoplasmic domain-associated protein 1 stimulates cellular proliferation [5].
• In summary, ICAP-1 (i) associates specifically with beta1 integrins, (ii) is phosphorylated upon beta1 integrin-mediated adhesion, and (iii) may regulate beta1-dependent cell migration [6].

Anatomical context of ITGB1BP1

• The interaction between ICAP-1 and KRIT1, and the presence of a FERM domain in the latter, suggest that KRIT1 might be involved in the bidirectional signaling between integrin molecules and the cytoskeleton [4].
• Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1 alpha [7].
• The plasma membrane localization of ROCK did not depend on beta1 integrin ligation or ROCK kinase activity, and in truncated ROCK proteins it required the presence of the ICAP-1-binding domain [8].
• In cells transfected with both ICAP-1 and ROCK, the proteins colocalized at the cell membrane predominantly in lamellipodia and membrane ruffles, but also in retraction fibers [8].

Associations of ITGB1BP1 with chemical compounds

• The alpha isoform of ICAP-1 is a 200 amino acid serine/threonine-rich phosphoprotein which binds the cytoplasmic tail of beta1 integrins [4].
• ICAP-1 is a ubiquitously expressed protein of 27 and 31 kDa, with the smaller form being preferentially solubilized by Triton X-100 [6].
• The integrin cytoplasmic domain-associated protein-1 (ICAP-1) binds via its C-terminal PTB (phosphotyrosine-binding) domain to the cytoplasmic tails of beta1 but not other integrins [8].
• The structure change during the growth processes was observed by transmission electron microscopy (TEM) and the variation in concentrations of gold species in the aqueous solution was monitored by UV-vis spectra and Inductively Coupled Argon Plasma Emission Spectrophotometer (ICAP) [9].

Other interactions of ITGB1BP1

• The novel N-terminus of krit1 contains a NPXY motif that it is required for icap1 interaction [3].
• Among those, the integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) has been shown to interact specifically with the beta(1) integrin cytoplasmic domain [10].
• KRIT1 binds SNX17 by its N-terminal region like the known interaction partner ICAP1alpha (integrin cytoplasmic domain-associated protein-1) [11].
• ILK, CD47 and ICAP1, as components of the intracellular signalling cascade of several integrins, were activated with ongoing dedifferentiation [12].

Analytical, diagnostic and therapeutic context of ITGB1BP1

• Interestingly, ICAP-1 also is observed in the nucleus, by immunocytochemical staining, and after biochemical cell fractionation, suggesting that it has additional roles that have yet to be determined [5].
• Using the yeast two-hybrid assay, we found that ICAP-1 binds the ROCK-I kinase, an effector of the RhoA GTPase [8].

References