UniProt Accession

 ITBP1_HUMAN; O14713; D6W4Y9; O14714; Q53RS0 

Genbank Protein ID

 AF012023; AF012024; CH471053; CH471053; CH471053; CH471053; AC080162; CH471053; CH471053; BC012264 

Genbank Nucleotide ID

 AAB88671.1; AAB88672.1; EAX00992.1; EAX00995.1; EAX01000.1; EAX01001.1; AAY14857.1; EAX00993.1; EAX00997.1; AAH12264.1 

Protein Name

 Integrin beta-1-binding protein 1 

Protein Synonyms/Alias

 Integrin cytoplasmic domain-associated protein 1; ICAP-1 

Gene Name

 ITGB1BP1 

Gene Synonyms/Alias

 ICAP1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
158	GKSLLALKTTDASNE	ubiquitination	[1]
199	DSVLTSEKP******	ubiquitination	[2]

Reference

 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 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 EKR1/2 phosphorylation through activation of the Notch signaling pathway. Promotes transcriptional activity of the MYC promoter. 

Sequence Annotation

 DOMAIN 58 200 PID.
 REGION 136 139 Interaction with KRIT1.
 REGION 139 141 Interaction with ITGB1.
 MOTIF 6 7 Nuclear localization signal.
 MOD_RES 38 38 Phosphothreonine; by CaMK2.  

Keyword

 3D-structure; Alternative splicing; Angiogenesis; Biomineralization; Cell adhesion; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Cytoskeleton; Differentiation; Membrane; Mitogen; Notch signaling pathway; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 200 AA 

Protein Sequence

Gene Ontology

 GO:0005856; C:cytoskeleton; ISS:UniProtKB.
 GO:0005829; C:cytosol; IDA:HGNC.
 GO:0030027; C:lamellipodium; IDA:HGNC.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; ISS:UniProtKB.
 GO:0001726; C:ruffle; IDA:HGNC.
 GO:0005092; F:GDP-dissociation inhibitor activity; IDA:UniProtKB.
 GO:0005178; F:integrin binding; IDA:UniProtKB.
 GO:0019901; F:protein kinase binding; ISS:UniProtKB.
 GO:0008565; F:protein transporter activity; IDA:UniProtKB.
 GO:0032148; P:activation of protein kinase B activity; IDA:UniProtKB.
 GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
 GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:UniProtKB.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0007160; P:cell-matrix adhesion; IDA:UniProtKB.
 GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
 GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
 GO:0033622; P:integrin activation; ISS:UniProtKB.
 GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
 GO:0007243; P:intracellular protein kinase cascade; TAS:ProtInc.
 GO:0051451; P:myoblast migration; ISS:UniProtKB.
 GO:0006933; P:negative regulation of cell adhesion involved in substrate-bound cell migration; ISS:UniProtKB.
 GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
 GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
 GO:0010764; P:negative regulation of fibroblast migration; ISS:UniProtKB.
 GO:0051895; P:negative regulation of focal adhesion assembly; IDA:UniProtKB.
 GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
 GO:0006469; P:negative regulation of protein kinase activity; IDA:UniProtKB.
 GO:0090315; P:negative regulation of protein targeting to membrane; IDA:UniProtKB.
 GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB.
 GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
 GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
 GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
 GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB.
 GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB.
 GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IDA:UniProtKB.
 GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
 GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0043113; P:receptor clustering; ISS:UniProtKB.
 GO:0050880; P:regulation of blood vessel size; IDA:UniProtKB.
 GO:0043088; P:regulation of Cdc42 GTPase activity; IDA:UniProtKB.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
 GO:2001044; P:regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0035148; P:tube formation; IDA:UniProtKB. 

Interpro

 IPR019517; Integrin-bd_ICAP-1.
 IPR011993; PH_like_dom.
 IPR006020; PTyr_interaction_dom. 

Pfam

 PF10480; ICAP-1_inte_bdg 

SMART

 SM00462; PTB 

PROSITE

 PS01179; PID 

PRINTS