O14713 (ITBP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Integrin beta-1-binding protein 1

Alternative name(s):
Integrin cytoplasmic domain-associated protein 1
Short name=ICAP-1

Gene names

Name:	ITGB1BP1
Synonyms:	ICAP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	200 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates integrin 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. May play a role in the recruitment of ITGB1 to focal contacts during integrin-dependent cell adhesion. Ref.8
Subunit structure	Interacts with KRIT1 and ITGB1; KRIT1 and ITGB1 compete for the same binding site. Isoform 2 does not interact with ITGB1. Ref.1 Ref.6 Ref.8
Subcellular location	Cytoplasm.
Tissue specificity	Expressed in intestine, colon, testis, ovary, thymus, spleen and prostate. Ref.1
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.
Sequence similarities	Contains 1 PID domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell migration Traceable author statement PubMed 11919189. Source: HGNC cell-matrix adhesion Inferred from direct assay Ref.1. Source: UniProtKB intracellular protein kinase cascade Traceable author statement Ref.5. Source: ProtInc
Cellular_component	cytosol Inferred from direct assay PubMed 11919189. Source: HGNC lamellipodium Inferred from direct assay PubMed 11919189. Source: HGNC membrane Non-traceable author statement Ref.1. Source: UniProtKB ruffle Inferred from direct assay PubMed 11919189. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NME2	P22392	7	EBI-2127367,EBI-713693

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O14713-1)

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.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 2 (identifier: O14713-2)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 200

200

Integrin beta-1-binding protein 1

PRO_0000084264

Regions

Domain

58 – 200

143

PID

Region

136 – 139

4

Interaction with KRIT1

Region

139 – 141

3

Interaction with ITGB1

Compositional bias

10 – 57

48

Ser/Thr-rich

Amino acid modifications

Modified residue

38

1

Phosphothreonine; by CaMK2 Ref.5

Natural variations

Alternative sequence

128 – 177

50

Missing in isoform 2.

VSP_003898

Experimental info

Mutagenesis

38

1

T → A: Stimulates cell spreading on fibronectin to a similar extent as inhibition of CaMKII. Ref.5 Ref.6

Mutagenesis

38

1

T → D: Changes in cell spreading. Ref.5 Ref.6

Mutagenesis

38

1

T → D: Strong defect in cell spreading. Ref.5 Ref.6

Mutagenesis

82

1

L → A: Reduces ITGB1 binding. Ref.6

Mutagenesis

82

1

L → Q: No effect on ITGB1 binding. Ref.6

Mutagenesis

86

1

L → Q: No effect on ITGB1 binding. Ref.6

Mutagenesis

89

1

I → R: Reduces KRIT1 binding. No effect on ITGB1 binding. Ref.8

Mutagenesis

93

1

D → A: Abolishes KRIT1 binding; when associated with A-96. Ref.8

Mutagenesis

96

1

Q → A: Abolishes KRIT1 binding; when associated with A-93. Ref.8

Mutagenesis

135 – 139

5

LYLII → AYAA: Reduces KRIT1 and ITGB1 binding. Ref.6 Ref.8

Mutagenesis

135

1

L → A: Abolishes ITGB1 binding. Ref.6

Mutagenesis

138

1

I → A: Abolishes ITGB1 binding. Ref.6

Mutagenesis

139

1

I → A: Abolishes ITGB1 binding. Ref.6

Mutagenesis

144

1

Y → T: Abolishes ITGB1 binding. Ref.6

Mutagenesis

184

1

C → D: Reduces KRIT1 and ITGB1 binding. Ref.8

Sequence conflict

150

1

A → V in AAH12264. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

200

Helix Strand Turn

Details...

Beta strand

61 – 75

15

Helix

84 – 97

14

Beta strand

99 – 101

3

Beta strand

110 – 115

6

Beta strand

118 – 123

6

Beta strand

129 – 134

6

Helix

135 – 137

3

Beta strand

138 – 145

8

Beta strand

148 – 150

3

Beta strand

153 – 160

8

Beta strand

167 – 176

10

Helix

177 – 195

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ICAP1-alpha) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0F041238E68FBE23	FASTA	200	21,782
	10 20 30 40 50 60 MFRKGKKRHS SSSSQSSEIS TKSKSVDSSL GGLSRSSTVA SLDTDSTKSS GQSNNNSDTC 70 80 90 100 110 120 AEFRIKYVGA IEKLKLSEGK GLEGPLDLIN YIDVAQQDGK LPFVPPEEEF IMGVSKYGIK 130 140 150 160 170 180 VSTSDQYDVL HRHALYLIIR MVCYDDGLGA GKSLLALKTT DASNEEYSLW VYQCNSLEQA 190 200 QAICKVLSTA FDSVLTSEKP
	Isoform 2 (ICAP1-beta) [UniParc]. Checksum: FC6E3D387878DB81	FASTA	150	16,140
	10 20 30 40 50 60 MFRKGKKRHS SSSSQSSEIS TKSKSVDSSL GGLSRSSTVA SLDTDSTKSS GQSNNNSDTC 70 80 90 100 110 120 AEFRIKYVGA IEKLKLSEGK GLEGPLDLIN YIDVAQQDGK LPFVPPEEEF IMGVSKYGIK 130 140 150 VSTSDQYEQA QAICKVLSTA FDSVLTSEKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin." Chang D.D., Wong C., Smith H., Liu J. J. Cell Biol. 138:1149-1157(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH ITGB1, PHOSPHORYLATION, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Ovary.
[5]	"Calcium/calmodulin-dependent protein kinase II controls integrin alpha5beta1-mediated cell adhesion through the integrin cytoplasmic domain associated protein-1alpha." Bouvard D., Block M.R. Biochem. Biophys. Res. Commun. 252:46-50(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-38, MUTAGENESIS OF THR-38.
[6]	"Molecular basis for interaction between Icap1alpha PTB domain and beta 1 integrin." Chang D.D., Hoang B.Q., Liu J., Springer T.A. J. Biol. Chem. 277:8140-8145(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ITGB1, MUTAGENESIS OF THR-38; LEU-82; LEU-86; LEU-135; ILE-138; ILE-139 AND TYR-144, 3D-STRUCTURE MODELING.
[7]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]	"Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation." Liu W., Draheim K.M., Zhang R., Calderwood D.A., Boggon T.J. Mol. Cell 0:0-0(2013) Cited for: X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 49-200 IN COMPLEXES WITH KRIT1 AND ITGB1, FUNCTION, INTERACTION WITH KRIT1 AND ITGB1, MUTAGENESIS OF ILE-89; ASP-93; GLN-96; 135-LEU--ILE-139 AND CYS-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00006265.
IPI00219566.

RefSeq

NP_004754.1. NM_004763.3.
NP_071729.1. NM_022334.3.

UniGene

Hs.467662.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K11	model	-	A	58-196	[»]
4DX8	X-ray	2.54	A/B/D/E	49-200	[»]
4DX9	X-ray	3.00	0/1/2/3/4/5/A/C/E/G/I/K/M/O/Q/S/U/W/Y/a/c/e/g/i/k/m/o/q/s/u/w/y	49-200	[»]

ProteinModelPortal

O14713.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14713. 5 interactions.

STRING

9606.ENSP00000347504.

PTM databases

PhosphoSite

O14713.

Proteomic databases

PaxDb

O14713.

PRIDE

O14713.

Protocols and materials databases

DNASU

9270.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000238091; ENSP00000238091; ENSG00000119185.
ENST00000355346; ENSP00000347504; ENSG00000119185.
ENST00000360635; ENSP00000353850; ENSG00000119185.
ENST00000488451; ENSP00000419524; ENSG00000119185.

GeneID

9270.

KEGG

hsa:9270.

UCSC

uc002qzj.3. human.
uc002qzk.3. human.

Organism-specific databases

CTD

9270.

GeneCards

GC02M009496.

HGNC

HGNC:23927. ITGB1BP1.

MIM

607153. gene.

neXtProt

NX_O14713.

PharmGKB

PA134913590.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45114.

HOGENOM

HOG000015089.

HOVERGEN

HBG052155.

InParanoid

O14713.

OMA

VLHRHPL.

OrthoDB

EOG483D5W.

PhylomeDB

O14713.

Gene expression databases

ArrayExpress

O14713.

Bgee

O14713.

CleanEx

HS_ITGB1BP1.

Genevestigator

O14713.

GermOnline

ENSG00000119185. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR019517. Integrin-bd_ICAP-1.
IPR011993. PH_like_dom.
IPR006020. PTyr_interaction_dom.
[Graphical view]

Pfam

PF10480. ICAP-1_inte_bdg. 1 hit.
[Graphical view]

SMART

SM00462. PTB. 1 hit.
[Graphical view]

PROSITE

PS01179. PID. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ITGB1BP1. human.

GenomeRNAi

9270.

NextBio

34745.

SOURCE

Search...

Entry information

Entry name

ITBP1_HUMAN

Accession

Primary (citable) accession number: O14713
Secondary accession number(s): D6W4Y9, O14714, Q53RS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.