ID ITBP1_HUMAN Reviewed; 200 AA. AC O14713; D6W4Y9; O14714; Q53RS0; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 06-MAR-2013, entry version 112. DE RecName: Full=Integrin beta-1-binding protein 1; DE AltName: Full=Integrin cytoplasmic domain-associated protein 1; DE Short=ICAP-1; GN Name=ITGB1BP1; Synonyms=ICAP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH ITGB1, RP PHOSPHORYLATION, AND TISSUE SPECIFICITY. RC TISSUE=Cervix carcinoma; RX MEDLINE=97428321; PubMed=9281591; DOI=10.1083/jcb.138.5.1149; RA Chang D.D., Wong C., Smith H., Liu J.; RT "ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, RT binds to a conserved and functionally important NPXY sequence motif of RT beta1 integrin."; RL J. Cell Biol. 138:1149-1157(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PHOSPHORYLATION AT THR-38, AND MUTAGENESIS OF THR-38. RX PubMed=9813144; DOI=10.1006/bbrc.1998.9592; RA Bouvard D., Block M.R.; RT "Calcium/calmodulin-dependent protein kinase II controls integrin RT alpha5beta1-mediated cell adhesion through the integrin cytoplasmic RT domain associated protein-1alpha."; RL Biochem. Biophys. Res. Commun. 252:46-50(1998). RN [6] RP INTERACTION WITH ITGB1, MUTAGENESIS OF THR-38; LEU-82; LEU-86; RP LEU-135; ILE-138; ILE-139 AND TYR-144, AND 3D-STRUCTURE MODELING. RX MEDLINE=21864153; PubMed=11741908; DOI=10.1074/jbc.M109031200; RA Chang D.D., Hoang B.Q., Liu J., Springer T.A.; RT "Molecular basis for interaction between Icap1alpha PTB domain and RT beta 1 integrin."; RL J. Biol. Chem. 277:8140-8145(2002). RN [7] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 49-200 IN COMPLEXES WITH RP KRIT1 AND ITGB1, FUNCTION, INTERACTION WITH KRIT1 AND ITGB1, AND RP MUTAGENESIS OF ILE-89; ASP-93; GLN-96; 135-LEU--ILE-139 AND CYS-184. RX DOI=10.1016/j.molcel.2012.12.005; RA Liu W., Draheim K.M., Zhang R., Calderwood D.A., Boggon T.J.; RT "Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin RT activation."; RL Mol. Cell 0:0-0(2013). CC -!- FUNCTION: Regulates integrin signaling by binding to the ITGB1 CC cytoplasmic tail and preventing the activation of integrin alpha- CC 5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. May CC play a role in the recruitment of ITGB1 to focal contacts during CC integrin-dependent cell adhesion. CC -!- SUBUNIT: Interacts with KRIT1 and ITGB1; KRIT1 and ITGB1 compete CC for the same binding site. Isoform 2 does not interact with ITGB1. CC -!- INTERACTION: CC P22392:NME2; NbExp=7; IntAct=EBI-2127367, EBI-713693; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=ICAP1-alpha; CC IsoId=O14713-1; Sequence=Displayed; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC Name=2; Synonyms=ICAP1-beta; CC IsoId=O14713-2; Sequence=VSP_003898; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC -!- TISSUE SPECIFICITY: Expressed in intestine, colon, testis, ovary, CC thymus, spleen and prostate. CC -!- PTM: Phosphorylation at Thr-38 seems to enhance integrin CC alpha5beta1-mediated cell adhesion. The degree of phosphorylation CC is regulated by integrin-dependent cell-matrix interaction. CC -!- SIMILARITY: Contains 1 PID domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF012023; AAB88671.1; -; mRNA. DR EMBL; AF012024; AAB88672.1; -; mRNA. DR EMBL; CH471053; EAX00992.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00995.1; -; Genomic_DNA. DR EMBL; CH471053; EAX01000.1; -; Genomic_DNA. DR EMBL; CH471053; EAX01001.1; -; Genomic_DNA. DR EMBL; AC080162; AAY14857.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00993.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00997.1; -; Genomic_DNA. DR EMBL; BC012264; AAH12264.1; -; mRNA. DR IPI; IPI00006265; -. DR IPI; IPI00219566; -. DR RefSeq; NP_004754.1; NM_004763.3. DR RefSeq; NP_071729.1; NM_022334.3. DR UniGene; Hs.467662; -. DR PDB; 1K11; Model; -; A=58-196. DR PDB; 4DX8; X-ray; 2.54 A; A/B/D/E=49-200. DR PDB; 4DX9; X-ray; 3.00 A; 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. DR PDBsum; 1K11; -. DR PDBsum; 4DX8; -. DR PDBsum; 4DX9; -. DR ProteinModelPortal; O14713; -. DR IntAct; O14713; 5. DR STRING; O14713; -. DR PhosphoSite; O14713; -. DR PaxDb; O14713; -. DR PRIDE; O14713; -. DR DNASU; 9270; -. DR Ensembl; ENST00000238091; ENSP00000238091; ENSG00000119185. DR Ensembl; ENST00000355346; ENSP00000347504; ENSG00000119185. DR Ensembl; ENST00000360635; ENSP00000353850; ENSG00000119185. DR Ensembl; ENST00000488451; ENSP00000419524; ENSG00000119185. DR GeneID; 9270; -. DR KEGG; hsa:9270; -. DR UCSC; uc002qzj.3; human. DR UCSC; uc002qzk.3; human. DR CTD; 9270; -. DR GeneCards; GC02M009496; -. DR HGNC; HGNC:23927; ITGB1BP1. DR MIM; 607153; gene. DR neXtProt; NX_O14713; -. DR PharmGKB; PA134913590; -. DR eggNOG; NOG45114; -. DR HOGENOM; HOG000015089; -. DR HOVERGEN; HBG052155; -. DR InParanoid; O14713; -. DR OMA; VLHRHPL; -. DR OrthoDB; EOG483D5W; -. DR PhylomeDB; O14713; -. DR ChiTaRS; ITGB1BP1; human. DR GenomeRNAi; 9270; -. DR NextBio; 34745; -. DR ArrayExpress; O14713; -. DR Bgee; O14713; -. DR CleanEx; HS_ITGB1BP1; -. DR Genevestigator; O14713; -. DR GermOnline; ENSG00000119185; Homo sapiens. DR GO; GO:0005829; C:cytosol; IDA:HGNC. DR GO; GO:0030027; C:lamellipodium; IDA:HGNC. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0001726; C:ruffle; IDA:HGNC. DR GO; GO:0016477; P:cell migration; TAS:HGNC. DR GO; GO:0007160; P:cell-matrix adhesion; IDA:UniProtKB. DR GO; GO:0007243; P:intracellular protein kinase cascade; TAS:ProtInc. DR Gene3D; 2.30.29.30; -; 1. DR InterPro; IPR019517; Integrin-bd_ICAP-1. DR InterPro; IPR011993; PH_like_dom. DR InterPro; IPR006020; PTyr_interaction_dom. DR Pfam; PF10480; ICAP-1_inte_bdg; 1. DR SMART; SM00462; PTB; 1. DR PROSITE; PS01179; PID; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; KW Phosphoprotein; Reference proteome. FT CHAIN 1 200 Integrin beta-1-binding protein 1. FT /FTId=PRO_0000084264. FT DOMAIN 58 200 PID. FT REGION 136 139 Interaction with KRIT1. FT REGION 139 141 Interaction with ITGB1. FT COMPBIAS 10 57 Ser/Thr-rich. FT MOD_RES 38 38 Phosphothreonine; by CaMK2. FT VAR_SEQ 128 177 Missing (in isoform 2). FT /FTId=VSP_003898. FT MUTAGEN 38 38 T->A: Stimulates cell spreading on FT fibronectin to a similar extent as FT inhibition of CaMKII. FT MUTAGEN 38 38 T->D: Changes in cell spreading. FT MUTAGEN 38 38 T->D: Strong defect in cell spreading. FT MUTAGEN 82 82 L->A: Reduces ITGB1 binding. FT MUTAGEN 82 82 L->Q: No effect on ITGB1 binding. FT MUTAGEN 86 86 L->Q: No effect on ITGB1 binding. FT MUTAGEN 89 89 I->R: Reduces KRIT1 binding. No effect on FT ITGB1 binding. FT MUTAGEN 93 93 D->A: Abolishes KRIT1 binding; when FT associated with A-96. FT MUTAGEN 96 96 Q->A: Abolishes KRIT1 binding; when FT associated with A-93. FT MUTAGEN 135 139 LYLII->AYAA: Reduces KRIT1 and ITGB1 FT binding. FT MUTAGEN 135 135 L->A: Abolishes ITGB1 binding. FT MUTAGEN 138 138 I->A: Abolishes ITGB1 binding. FT MUTAGEN 139 139 I->A: Abolishes ITGB1 binding. FT MUTAGEN 144 144 Y->T: Abolishes ITGB1 binding. FT MUTAGEN 184 184 C->D: Reduces KRIT1 and ITGB1 binding. FT CONFLICT 150 150 A -> V (in Ref. 4; AAH12264). FT STRAND 61 73 FT HELIX 80 97 FT STRAND 109 114 FT STRAND 116 123 FT TURN 124 126 FT STRAND 129 134 FT TURN 135 137 FT STRAND 138 144 FT STRAND 154 160 FT STRAND 162 165 FT STRAND 167 174 FT HELIX 176 193 SQ SEQUENCE 200 AA; 21782 MW; 0F041238E68FBE23 CRC64; MFRKGKKRHS SSSSQSSEIS TKSKSVDSSL GGLSRSSTVA SLDTDSTKSS GQSNNNSDTC AEFRIKYVGA IEKLKLSEGK GLEGPLDLIN YIDVAQQDGK LPFVPPEEEF IMGVSKYGIK VSTSDQYDVL HRHALYLIIR MVCYDDGLGA GKSLLALKTT DASNEEYSLW VYQCNSLEQA QAICKVLSTA FDSVLTSEKP //