InnateDB Protein
|
IDBP-27500.6
|
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
|
ENSP00000353850
|
InnateDB Gene
|
IDBG-27498 (ITGB1BP1)
|
Protein Structure
|
|
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 |
|
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
|
|
|
|
Molecular Function |
|
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:0051894
|
positive regulation of focal adhesion assembly
|
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 |
|
PDB ID |
|
InterPro |
IPR006020
PTB/PI domain
IPR019517
Integrin binding protein, ICAP-1
|
PFAM |
PF00640
PF14719
PF10480
|
PRINTS |
|
PIRSF |
|
SMART |
SM00462
|
TIGRFAMs |
|
Modification |
|
SwissProt |
O14713
|
PhosphoSite |
PhosphoSite-O14713
|
TrEMBL |
C9JZ07
|
UniProt Splice Variant |
|
Entrez Gene |
9270
|
UniGene |
Hs.695627
|
RefSeq |
XP_005246240
|
HUGO |
HGNC:23927
|
OMIM |
607153
|
CCDS |
CCDS1662
|
HPRD |
06194
|
IMGT |
|
EMBL |
AC080162
AF012023
AF012024
BC012264
CH471053
|
GenPept |
AAB88671
AAB88672
AAH12264
AAY14857
EAX00992
EAX00993
EAX00995
EAX00997
EAX01000
EAX01001
|
|
|