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Protein

Integrin beta-1-binding protein 1

Gene

ITGB1BP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.9 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMitogen
Biological processAngiogenesis, Biomineralization, Cell adhesion, Differentiation, Notch signaling pathway, Transcription, Transcription regulation

Enzyme and pathway databases

SIGNORiO14713

Names & Taxonomyi

Protein namesi
Recommended name:
Integrin beta-1-binding protein 1
Alternative name(s):
Integrin cytoplasmic domain-associated protein 1
Short name:
ICAP-1
Gene namesi
Name:ITGB1BP1
Synonyms:ICAP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000119185.12
HGNCiHGNC:23927 ITGB1BP1
MIMi607153 gene
neXtProtiNX_O14713

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi6 – 7KK → AA: Abolishes nuclear import and transcriptional activity. 1 Publication2
Mutagenesisi38T → A: Stimulates cell spreading on fibronectin to a similar extent as inhibition of CaMKII. 2 Publications1
Mutagenesisi38T → D: Changes in cell spreading. 2 Publications1
Mutagenesisi38T → D: Strong defect in cell spreading. 2 Publications1
Mutagenesisi82L → A: Reduces ITGB1 binding. 1 Publication1
Mutagenesisi82L → Q: No effect on ITGB1 binding. 1 Publication1
Mutagenesisi86L → Q: No effect on ITGB1 binding. 1 Publication1
Mutagenesisi89I → R: Reduces KRIT1 binding. No effect on ITGB1 binding. 1 Publication1
Mutagenesisi93D → A: Abolishes KRIT1 binding; when associated with A-96. 1 Publication1
Mutagenesisi96Q → A: Abolishes KRIT1 binding; when associated with A-93. 1 Publication1
Mutagenesisi135 – 139LYLII → AYAA: Reduces KRIT1 and ITGB1 binding. 1 Publication5
Mutagenesisi135L → A: Abolishes ITGB1 binding. 1 Publication1
Mutagenesisi138I → A: Abolishes ITGB1 binding. 2 Publications1
Mutagenesisi139I → A: Abolishes ITGB1 binding. 1 Publication1
Mutagenesisi144Y → T: Abolishes ITGB1 binding. 1 Publication1
Mutagenesisi184C → D: Reduces KRIT1 and ITGB1 binding. 1 Publication1

Organism-specific databases

DisGeNETi9270
OpenTargetsiENSG00000119185
PharmGKBiPA134913590

Polymorphism and mutation databases

BioMutaiITGB1BP1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842641 – 200Integrin beta-1-binding protein 1Add BLAST200

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38Phosphothreonine; by CaMK21 Publication1
Modified residuei41PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-38 seems to enhance integrin alpha5beta1-mediated cell adhesion. The degree of phosphorylation is regulated by integrin-dependent cell-matrix interaction.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO14713
MaxQBiO14713
PaxDbiO14713
PeptideAtlasiO14713
PRIDEiO14713
ProteomicsDBi48172
48173 [O14713-2]

PTM databases

iPTMnetiO14713
PhosphoSitePlusiO14713

Expressioni

Tissue specificityi

Expressed in endothelial cells and fibroblasts (at protein level). Ubiquitously expressed. Expressed in intestine, colon, testis, ovary, thymus, spleen and prostate.2 Publications

Gene expression databases

BgeeiENSG00000119185 Expressed in 237 organ(s), highest expression level in caudate nucleus
CleanExiHS_ITGB1BP1
ExpressionAtlasiO14713 baseline and differential
GenevisibleiO14713 HS

Organism-specific databases

HPAiHPA067348
HPA071538

Interactioni

Subunit structurei

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.By similarity11 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114689, 16 interactors
CORUMiO14713
IntActiO14713, 12 interactors
MINTiO14713
STRINGi9606.ENSP00000347504

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14713
SMRiO14713
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini58 – 200PIDAdd BLAST143

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni136 – 139Interaction with KRIT14
Regioni139 – 141Interaction with ITGB13

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi6 – 7Nuclear localization signal2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 57Ser/Thr-richAdd BLAST48

Phylogenomic databases

eggNOGiENOG410IFN6 Eukaryota
ENOG4111GWT LUCA
GeneTreeiENSGT00390000003990
HOGENOMiHOG000015089
HOVERGENiHBG052155
InParanoidiO14713
KOiK20058
OMAiRMLCYDD
OrthoDBiEOG091G16AY
PhylomeDBiO14713
TreeFamiTF105393

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR019517 Integrin-bd_ICAP-1
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
PANTHERiPTHR32055 PTHR32055, 1 hit
PfamiView protein in Pfam
PF10480 ICAP-1_inte_bdg, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O14713-1) [UniParc]FASTAAdd to basket
Also known as: ICAP1-alpha

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.

« Hide
        10         20         30         40         50
MFRKGKKRHS SSSSQSSEIS TKSKSVDSSL GGLSRSSTVA SLDTDSTKSS
60 70 80 90 100
GQSNNNSDTC AEFRIKYVGA IEKLKLSEGK GLEGPLDLIN YIDVAQQDGK
110 120 130 140 150
LPFVPPEEEF IMGVSKYGIK VSTSDQYDVL HRHALYLIIR MVCYDDGLGA
160 170 180 190 200
GKSLLALKTT DASNEEYSLW VYQCNSLEQA QAICKVLSTA FDSVLTSEKP
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Length:200
Mass (Da):21,782
Last modified:January 1, 1998 - v1
Checksum:i0F041238E68FBE23
GO
Isoform 2 (identifier: O14713-2) [UniParc]FASTAAdd to basket
Also known as: ICAP1-beta

The sequence of this isoform differs from the canonical sequence as follows:
     128-177: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:150
Mass (Da):16,140
Checksum:iFC6E3D387878DB81
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A8MPU2A8MPU2_HUMAN
Integrin beta 1 binding protein 1, ...
ITGB1BP1 hCG_1686416
184Annotation score:
C9JBU8C9JBU8_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
136Annotation score:
C9J5T5C9J5T5_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
114Annotation score:
C9JZ07C9JZ07_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
96Annotation score:
C9J0J6C9J0J6_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
86Annotation score:
C9J6Y2C9J6Y2_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
84Annotation score:
C9IZZ8C9IZZ8_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
65Annotation score:
G3V1A3G3V1A3_HUMAN
Integrin beta 1 binding protein 1, ...
ITGB1BP1 hCG_1686416
107Annotation score:
F8WF20F8WF20_HUMAN
Integrin beta-1-binding protein 1
ITGB1BP1
38Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti150A → V in AAH12264 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003898128 – 177Missing in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF012023 mRNA Translation: AAB88671.1
AF012024 mRNA Translation: AAB88672.1
CH471053 Genomic DNA Translation: EAX00992.1
CH471053 Genomic DNA Translation: EAX00995.1
CH471053 Genomic DNA Translation: EAX01000.1
CH471053 Genomic DNA Translation: EAX01001.1
AC080162 Genomic DNA Translation: AAY14857.1
CH471053 Genomic DNA Translation: EAX00993.1
CH471053 Genomic DNA Translation: EAX00997.1
BC012264 mRNA Translation: AAH12264.1
CCDSiCCDS1662.1 [O14713-1]
CCDS1663.1 [O14713-2]
RefSeqiNP_001305995.1, NM_001319066.1 [O14713-1]
NP_001305996.1, NM_001319067.1 [O14713-1]
NP_001305997.1, NM_001319068.1 [O14713-1]
NP_004754.1, NM_004763.4 [O14713-1]
NP_071729.1, NM_022334.4 [O14713-2]
XP_005246240.1, XM_005246183.4 [O14713-1]
XP_005246241.1, XM_005246184.4 [O14713-1]
XP_005246242.1, XM_005246185.4 [O14713-1]
XP_005246246.1, XM_005246189.4 [O14713-2]
XP_006711966.1, XM_006711903.3 [O14713-1]
XP_011508718.1, XM_011510416.2 [O14713-1]
XP_016860756.1, XM_017005267.1 [O14713-1]
XP_016860757.1, XM_017005268.1 [O14713-1]
XP_016860758.1, XM_017005269.1 [O14713-2]
XP_016860759.1, XM_017005270.1 [O14713-2]
UniGeneiHs.467662

Genome annotation databases

EnsembliENST00000238091; ENSP00000238091; ENSG00000119185 [O14713-2]
ENST00000355346; ENSP00000347504; ENSG00000119185 [O14713-1]
ENST00000360635; ENSP00000353850; ENSG00000119185 [O14713-1]
ENST00000488451; ENSP00000419524; ENSG00000119185 [O14713-2]
GeneIDi9270
KEGGihsa:9270
UCSCiuc002qzj.4 human [O14713-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF012023 mRNA Translation: AAB88671.1
AF012024 mRNA Translation: AAB88672.1
CH471053 Genomic DNA Translation: EAX00992.1
CH471053 Genomic DNA Translation: EAX00995.1
CH471053 Genomic DNA Translation: EAX01000.1
CH471053 Genomic DNA Translation: EAX01001.1
AC080162 Genomic DNA Translation: AAY14857.1
CH471053 Genomic DNA Translation: EAX00993.1
CH471053 Genomic DNA Translation: EAX00997.1
BC012264 mRNA Translation: AAH12264.1
CCDSiCCDS1662.1 [O14713-1]
CCDS1663.1 [O14713-2]
RefSeqiNP_001305995.1, NM_001319066.1 [O14713-1]
NP_001305996.1, NM_001319067.1 [O14713-1]
NP_001305997.1, NM_001319068.1 [O14713-1]
NP_004754.1, NM_004763.4 [O14713-1]
NP_071729.1, NM_022334.4 [O14713-2]
XP_005246240.1, XM_005246183.4 [O14713-1]
XP_005246241.1, XM_005246184.4 [O14713-1]
XP_005246242.1, XM_005246185.4 [O14713-1]
XP_005246246.1, XM_005246189.4 [O14713-2]
XP_006711966.1, XM_006711903.3 [O14713-1]
XP_011508718.1, XM_011510416.2 [O14713-1]
XP_016860756.1, XM_017005267.1 [O14713-1]
XP_016860757.1, XM_017005268.1 [O14713-1]
XP_016860758.1, XM_017005269.1 [O14713-2]
XP_016860759.1, XM_017005270.1 [O14713-2]
UniGeneiHs.467662

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K11model-A58-196[»]
4DX8X-ray2.54A/B/D/E49-200[»]
4DX9X-ray2.990/1/2/3/4/5/A/C/E/G/I/K/M/O/Q/S/U/W/Y/a/c/e/g/i/k/m/o/q/s/u49-200[»]
4JIFX-ray1.70A49-200[»]
ProteinModelPortaliO14713
SMRiO14713
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114689, 16 interactors
CORUMiO14713
IntActiO14713, 12 interactors
MINTiO14713
STRINGi9606.ENSP00000347504

PTM databases

iPTMnetiO14713
PhosphoSitePlusiO14713

Polymorphism and mutation databases

BioMutaiITGB1BP1

Proteomic databases

EPDiO14713
MaxQBiO14713
PaxDbiO14713
PeptideAtlasiO14713
PRIDEiO14713
ProteomicsDBi48172
48173 [O14713-2]

Protocols and materials databases

DNASUi9270
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000238091; ENSP00000238091; ENSG00000119185 [O14713-2]
ENST00000355346; ENSP00000347504; ENSG00000119185 [O14713-1]
ENST00000360635; ENSP00000353850; ENSG00000119185 [O14713-1]
ENST00000488451; ENSP00000419524; ENSG00000119185 [O14713-2]
GeneIDi9270
KEGGihsa:9270
UCSCiuc002qzj.4 human [O14713-1]

Organism-specific databases

CTDi9270
DisGeNETi9270
EuPathDBiHostDB:ENSG00000119185.12
GeneCardsiITGB1BP1
HGNCiHGNC:23927 ITGB1BP1
HPAiHPA067348
HPA071538
MIMi607153 gene
neXtProtiNX_O14713
OpenTargetsiENSG00000119185
PharmGKBiPA134913590
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFN6 Eukaryota
ENOG4111GWT LUCA
GeneTreeiENSGT00390000003990
HOGENOMiHOG000015089
HOVERGENiHBG052155
InParanoidiO14713
KOiK20058
OMAiRMLCYDD
OrthoDBiEOG091G16AY
PhylomeDBiO14713
TreeFamiTF105393

Enzyme and pathway databases

SIGNORiO14713

Miscellaneous databases

ChiTaRSiITGB1BP1 human
GeneWikiiITGB1BP1
GenomeRNAii9270
PROiPR:O14713
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119185 Expressed in 237 organ(s), highest expression level in caudate nucleus
CleanExiHS_ITGB1BP1
ExpressionAtlasiO14713 baseline and differential
GenevisibleiO14713 HS

Family and domain databases

Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR019517 Integrin-bd_ICAP-1
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
PANTHERiPTHR32055 PTHR32055, 1 hit
PfamiView protein in Pfam
PF10480 ICAP-1_inte_bdg, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiITBP1_HUMAN
AccessioniPrimary (citable) accession number: O14713
Secondary accession number(s): D6W4Y9, O14714, Q53RS0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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