O14713 · ITBP1_HUMAN
- ProteinIntegrin beta-1-binding protein 1
- GeneITGB1BP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids200 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameIntegrin beta-1-binding protein 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO14713
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 6-7 | Abolishes nuclear import and transcriptional activity. | ||||
Sequence: KK → AA | ||||||
Mutagenesis | 38 | Stimulates cell spreading on fibronectin to a similar extent as inhibition of CaMKII. | ||||
Sequence: T → A | ||||||
Mutagenesis | 38 | Changes in cell spreading. | ||||
Sequence: T → D | ||||||
Mutagenesis | 38 | Strong defect in cell spreading. | ||||
Sequence: T → D | ||||||
Mutagenesis | 82 | Reduces ITGB1 binding. | ||||
Sequence: L → A | ||||||
Mutagenesis | 82 | No effect on ITGB1 binding. | ||||
Sequence: L → Q | ||||||
Mutagenesis | 86 | No effect on ITGB1 binding. | ||||
Sequence: L → Q | ||||||
Mutagenesis | 89 | Reduces KRIT1 binding. No effect on ITGB1 binding. | ||||
Sequence: I → R | ||||||
Mutagenesis | 93 | Abolishes KRIT1 binding; when associated with A-96. | ||||
Sequence: D → A | ||||||
Mutagenesis | 96 | Abolishes KRIT1 binding; when associated with A-93. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 135 | Abolishes ITGB1 binding. | ||||
Sequence: L → A | ||||||
Mutagenesis | 135-139 | Reduces KRIT1 and ITGB1 binding. | ||||
Sequence: LYLII → AYAA | ||||||
Mutagenesis | 138 | Abolishes ITGB1 binding. | ||||
Sequence: I → A | ||||||
Mutagenesis | 139 | Abolishes ITGB1 binding. | ||||
Sequence: I → A | ||||||
Mutagenesis | 144 | Abolishes ITGB1 binding. | ||||
Sequence: Y → T | ||||||
Mutagenesis | 184 | Reduces KRIT1 and ITGB1 binding. | ||||
Sequence: C → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 232 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000084264 | 1-200 | UniProt | Integrin beta-1-binding protein 1 | |||
Sequence: MFRKGKKRHSSSSSQSSEISTKSKSVDSSLGGLSRSSTVASLDTDSTKSSGQSNNNSDTCAEFRIKYVGAIEKLKLSEGKGLEGPLDLINYIDVAQQDGKLPFVPPEEEFIMGVSKYGIKVSTSDQYDVLHRHALYLIIRMVCYDDGLGAGKSLLALKTTDASNEEYSLWVYQCNSLEQAQAICKVLSTAFDSVLTSEKP | |||||||
Modified residue (large scale data) | 11 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 13 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 25 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 28 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 29 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 34 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 38 | UniProt | Phosphothreonine; by CaMK2 | ||||
Sequence: T | |||||||
Modified residue | 41 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 41 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 49 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation at Thr-38 seems to enhance integrin alpha5beta1-mediated cell adhesion. The degree of phosphorylation is regulated by integrin-dependent cell-matrix interaction.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in endothelial cells and fibroblasts (at protein level). Ubiquitously expressed. Expressed in intestine, colon, testis, ovary, thymus, spleen and prostate.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts (via N-terminus and PTB domain) with ROCK1 (By similarity).
Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminal region) with ITGB1 (via C-terminal cytoplasmic tail); the interaction prevents talin TLN1 binding to ITGB1 and KRIT1 and ITGB1 compete for the same binding site. Interacts with KRIT1 (via N-terminal NPXY motif); the interaction induces the opening conformation of KRIT1 and KRIT1 and ITGB1 compete for the same binding site. Isoform 2 does not interact with ITGB1. Interacts with CDC42 (GTP- or GDP-bound form); the interaction is increased with the CDC42-membrane bound forms and prevents both CDC42 activation and cell spreading. Interacts (via C-terminal domain region) with NME2. Interacts with FERMT2 and RAC1.
Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminal region) with ITGB1 (via C-terminal cytoplasmic tail); the interaction prevents talin TLN1 binding to ITGB1 and KRIT1 and ITGB1 compete for the same binding site. Interacts with KRIT1 (via N-terminal NPXY motif); the interaction induces the opening conformation of KRIT1 and KRIT1 and ITGB1 compete for the same binding site. Isoform 2 does not interact with ITGB1. Interacts with CDC42 (GTP- or GDP-bound form); the interaction is increased with the CDC42-membrane bound forms and prevents both CDC42 activation and cell spreading. Interacts (via C-terminal domain region) with NME2. Interacts with FERMT2 and RAC1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O14713 | ATXN1 P54253 | 3 | EBI-2127319, EBI-930964 | |
BINARY | O14713 | DLD P09622 | 3 | EBI-2127319, EBI-353366 | |
BINARY | O14713 | FIGNL1 Q6PIW4 | 3 | EBI-2127319, EBI-8468390 | |
BINARY | O14713 | KRIT1 O00522 | 5 | EBI-2127319, EBI-1573121 | |
BINARY | O14713 | RHOH Q15669 | 3 | EBI-2127319, EBI-1244971 | |
BINARY | O14713 | SNCA P37840 | 3 | EBI-2127319, EBI-985879 | |
BINARY | O14713 | SOD1 P00441 | 3 | EBI-2127319, EBI-990792 | |
BINARY | O14713-1 | NME2 P22392 | 7 | EBI-2127367, EBI-713693 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-56 | Disordered | ||||
Sequence: MFRKGKKRHSSSSSQSSEISTKSKSVDSSLGGLSRSSTVASLDTDSTKSSGQSNNN | ||||||
Motif | 6-7 | Nuclear localization signal | ||||
Sequence: KK | ||||||
Compositional bias | 12-56 | Polar residues | ||||
Sequence: SSSQSSEISTKSKSVDSSLGGLSRSSTVASLDTDSTKSSGQSNNN | ||||||
Domain | 58-200 | PID | ||||
Sequence: DTCAEFRIKYVGAIEKLKLSEGKGLEGPLDLINYIDVAQQDGKLPFVPPEEEFIMGVSKYGIKVSTSDQYDVLHRHALYLIIRMVCYDDGLGAGKSLLALKTTDASNEEYSLWVYQCNSLEQAQAICKVLSTAFDSVLTSEKP | ||||||
Region | 136-139 | Interaction with KRIT1 | ||||
Sequence: YLII | ||||||
Region | 139-141 | Interaction with ITGB1 | ||||
Sequence: IRM |
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O14713-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsICAP1-alpha
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
- Length200
- Mass (Da)21,782
- Last updated1998-01-01 v1
- Checksum0F041238E68FBE23
O14713-2
- Name2
- SynonymsICAP1-beta
- NoteMay be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
- Differences from canonical
- 128-177: Missing
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 12-56 | Polar residues | ||||
Sequence: SSSQSSEISTKSKSVDSSLGGLSRSSTVASLDTDSTKSSGQSNNN | ||||||
Alternative sequence | VSP_003898 | 128-177 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 150 | in Ref. 4; AAH12264 | ||||
Sequence: A → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF012023 EMBL· GenBank· DDBJ | AAB88671.1 EMBL· GenBank· DDBJ | mRNA | ||
AF012024 EMBL· GenBank· DDBJ | AAB88672.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00992.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00995.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX01000.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX01001.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC080162 EMBL· GenBank· DDBJ | AAY14857.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00993.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00997.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC012264 EMBL· GenBank· DDBJ | AAH12264.1 EMBL· GenBank· DDBJ | mRNA |