ID ITA5_HUMAN Reviewed; 1049 AA. AC P08648; Q96HA5; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2002, sequence version 2. DT 01-MAY-2013, entry version 153. DE RecName: Full=Integrin alpha-5; DE AltName: Full=CD49 antigen-like family member E; DE AltName: Full=Fibronectin receptor subunit alpha; DE AltName: Full=Integrin alpha-F; DE AltName: Full=VLA-5; DE AltName: CD_antigen=CD49e; DE Contains: DE RecName: Full=Integrin alpha-5 heavy chain; DE Contains: DE RecName: Full=Integrin alpha-5 light chain; DE Flags: Precursor; GN Name=ITGA5; Synonyms=FNRA; 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]. RX PubMed=2958481; DOI=10.1083/jcb.105.3.1183; RA Argraves W.S., Suzuki S., Arai H., Thompson K., Pierschbacher M.D., RA Ruoslahti E.; RT "Amino acid sequence of the human fibronectin receptor."; RL J. Cell Biol. 105:1183-1190(1987). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-73. RX PubMed=1834647; RA Birkenmeier T.M., McQuillan J.J., Boedeker E.D., Argraves W.S., RA Ruoslahti E., Dean D.C.; RT "The alpha 5 beta 1 fibronectin receptor. Characterization of the RT alpha 5 gene promoter."; RL J. Biol. Chem. 266:20544-20549(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-1049. RX PubMed=2450560; DOI=10.1021/bi00399a021; RA Fitzgerald L.A., Poncz M., Steiner B., Rall S.C., Bennett J.S., RA Phillips D.R.; RT "Comparison of cDNA-derived protein sequences of the human fibronectin RT and vitronectin receptor alpha-subunits and platelet glycoprotein RT IIb."; RL Biochemistry 26:8158-8165(1987). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 821-1049. RX PubMed=2944883; RA Argraves W.S., Pytela R., Suzuki S., Millan J.L., Pierschbacher M.D., RA Ruoslahti E.; RT "cDNA sequences from the alpha subunit of the fibronectin receptor RT predict a transmembrane domain and a short cytoplasmic peptide."; RL J. Biol. Chem. 261:12922-12924(1986). RN [6] RP PROTEIN SEQUENCE OF 42-55. RX PubMed=3033641; DOI=10.1073/pnas.84.10.3239; RA Takada Y., Strominger J.L., Hemler M.E.; RT "The very late antigen family of heterodimers is part of a superfamily RT of molecules involved in adhesion and embryogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 84:3239-3243(1987). RN [7] RP INTERACTION WITH HIV-1 TAT. RX PubMed=10397733; RA Barillari G., Sgadari C., Fiorelli V., Samaniego F., Colombini S., RA Manzari V., Modesti A., Nair B.C., Cafaro A., Stuerzl M., Ensoli B.; RT "The Tat protein of human immunodeficiency virus type-1 promotes RT vascular cell growth and locomotion by engaging the alpha5beta1 and RT alphavbeta3 integrins and by mobilizing sequestered basic fibroblast RT growth factor."; RL Blood 94:663-672(1999). RN [8] RP INTERACTION WITH NISCH. RX PubMed=11912194; DOI=10.1074/jbc.M111838200; RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.; RT "Insulin receptor substrate 4 associates with the protein IRAS."; RL J. Biol. Chem. 277:19439-19447(2002). RN [9] RP DISULFIDE BONDS. RX PubMed=14596610; DOI=10.1021/bi034726u; RA Krokhin O.V., Cheng K., Sousa S.L., Ens W., Standing K.G., RA Wilkins J.A.; RT "Mass spectrometric based mapping of the disulfide bonding patterns of RT integrin alpha chains."; RL Biochemistry 42:12950-12959(2003). RN [10] RP INTERACTION WITH COMP. RX PubMed=16051604; DOI=10.1074/jbc.M504778200; RA Chen F.-H., Thomas A.O., Hecht J.T., Goldring M.B., Lawler J.; RT "Cartilage oligomeric matrix protein/thrombospondin 5 supports RT chondrocyte attachment through interaction with integrins."; RL J. Biol. Chem. 280:32655-32661(2005). RN [11] RP INTERACTION WITH RAB21. RX PubMed=16754960; DOI=10.1083/jcb.200509019; RA Pellinen T., Arjonen A., Vuoriluoto K., Kallio K., Fransen J.A.M., RA Ivaska J.; RT "Small GTPase Rab21 regulates cell adhesion and controls endosomal RT traffic of beta1-integrins."; RL J. Cell Biol. 173:767-780(2006). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-675 AND RP ASN-773, AND MASS SPECTROMETRY. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-771 AND RP ASN-773, AND MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N- RT linked cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP PROTEOLYTIC CLEAVAGE BY PCSK5. RX PubMed=22740495; DOI=10.1093/humrep/des203; RA Paule S., Aljofan M., Simon C., Rombauts L.J., Nie G.; RT "Cleavage of endometrial alpha-integrins into their functional forms RT is mediated by proprotein convertase 5/6."; RL Hum. Reprod. 27:2766-2774(2012). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 42-664 IN COMPLEX WITH RP ANTIBODY; ITGB1 AND RGD PEPTIDE, DISULFIDE BONDS, GLYCOSYLATION AT RP ASN-84; ASN-182; ASN-297; ASN-307; ASN-316 AND ASN-609, RP SUBSTRATE-BINDING SITES, CALCIUM-BINDING SITES, AND SUBUNIT. RX PubMed=22451694; DOI=10.1083/jcb.201111077; RA Nagae M., Re S., Mihara E., Nogi T., Sugita Y., Takagi J.; RT "Crystal structure of alpha5beta1 integrin ectodomain: atomic details RT of the fibronectin receptor."; RL J. Cell Biol. 197:131-140(2012). CC -!- FUNCTION: Integrin alpha-5/beta-1 is a receptor for fibronectin CC and fibrinogen. It recognizes the sequence R-G-D in its ligands. CC In case of HIV-1 infection, the interaction with extracellular CC viral Tat protein seems to enhance angiogenesis in Kaposi's CC sarcoma lesions. CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha CC subunit is composed of a heavy and a light chain linked by a CC disulfide bond. Alpha-5 associates with beta-1. Interacts with CC HPS5 and NISCH. Interacts with RAB21 and COMP. Interacts with HIV- CC 1 Tat. CC -!- INTERACTION: CC Q9H0F6:SHARPIN; NbExp=4; IntAct=EBI-1382311, EBI-3942966; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- PTM: Proteolytic cleavage by PCSK5 mediates activation of the CC precursor. CC -!- SIMILARITY: Belongs to the integrin alpha chain family. CC -!- SIMILARITY: Contains 7 FG-GAP repeats. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X06256; CAA29601.1; -; mRNA. DR EMBL; BC008786; AAH08786.1; -; mRNA. DR EMBL; M13918; AAA52467.1; ALT_SEQ; mRNA. DR IPI; IPI00306604; -. DR PIR; A27079; A27079. DR RefSeq; NP_002196.2; NM_002205.2. DR UniGene; Hs.505654; -. DR PDB; 3VI3; X-ray; 2.90 A; A/C=42-664. DR PDB; 3VI4; X-ray; 2.90 A; A/C=42-664. DR PDBsum; 3VI3; -. DR PDBsum; 3VI4; -. DR ProteinModelPortal; P08648; -. DR DIP; DIP-40037N; -. DR IntAct; P08648; 10. DR MINT; MINT-5005934; -. DR STRING; 9606.ENSP00000293379; -. DR GlycoSuiteDB; P08648; -. DR PhosphoSite; P08648; -. DR DMDM; 23831237; -. DR PaxDb; P08648; -. DR PeptideAtlas; P08648; -. DR PRIDE; P08648; -. DR DNASU; 3678; -. DR Ensembl; ENST00000293379; ENSP00000293379; ENSG00000161638. DR GeneID; 3678; -. DR KEGG; hsa:3678; -. DR UCSC; uc001sga.3; human. DR CTD; 3678; -. DR GeneCards; GC12M054789; -. DR HGNC; HGNC:6141; ITGA5. DR HPA; CAB009008; -. DR HPA; HPA002642; -. DR MIM; 135620; gene. DR neXtProt; NX_P08648; -. DR PharmGKB; PA29941; -. DR eggNOG; NOG26407; -. DR HOGENOM; HOG000231603; -. DR HOVERGEN; HBG006186; -. DR InParanoid; P08648; -. DR KO; K06484; -. DR OMA; ERSCSLE; -. DR OrthoDB; EOG43JC3X; -. DR PhylomeDB; P08648; -. DR Pathway_Interaction_DB; angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling. DR Pathway_Interaction_DB; syndecan_2_pathway; Syndecan-2-mediated signaling events. DR Pathway_Interaction_DB; syndecan_4_pathway; Syndecan-4-mediated signaling events. DR Pathway_Interaction_DB; lymphangiogenesis_pathway; VEGFR3 signaling in lymphatic endothelium. DR Reactome; REACT_111045; Developmental Biology. DR Reactome; REACT_111102; Signal Transduction. DR Reactome; REACT_118779; Extracellular matrix organization. DR Reactome; REACT_604; Hemostasis. DR BindingDB; P08648; -. DR ChEMBL; CHEMBL3955; -. DR GenomeRNAi; 3678; -. DR NextBio; 14395; -. DR ArrayExpress; P08648; -. DR Bgee; P08648; -. DR CleanEx; HS_ITGA5; -. DR Genevestigator; P08648; -. DR GermOnline; ENSG00000161638; Homo sapiens. DR GO; GO:0071062; C:alphav-beta3 integrin-vitronectin complex; TAS:BHF-UCL. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Compara. DR GO; GO:0008305; C:integrin complex; TAS:ProtInc. DR GO; GO:0001726; C:ruffle; TAS:HGNC. DR GO; GO:0045202; C:synapse; IEA:Compara. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; TAS:BHF-UCL. DR GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; TAS:BHF-UCL. DR GO; GO:0001525; P:angiogenesis; TAS:BHF-UCL. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0033631; P:cell-cell adhesion mediated by integrin; IEA:Compara. DR GO; GO:0007044; P:cell-substrate junction assembly; IEA:Compara. DR GO; GO:0007157; P:heterophilic cell-cell adhesion; IEA:Compara. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IEA:Compara. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0007613; P:memory; IEA:Compara. DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:BHF-UCL. DR GO; GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; IEP:BHF-UCL. DR InterPro; IPR013517; FG-GAP. DR InterPro; IPR013519; Int_alpha_beta-p. DR InterPro; IPR000413; Integrin_alpha. DR InterPro; IPR013649; Integrin_alpha-2. DR InterPro; IPR018184; Integrin_alpha_C_CS. DR Pfam; PF01839; FG-GAP; 3. DR Pfam; PF08441; Integrin_alpha2; 1. DR PRINTS; PR01185; INTEGRINA. DR SMART; SM00191; Int_alpha; 5. DR PROSITE; PS51470; FG_GAP; 7. DR PROSITE; PS00242; INTEGRIN_ALPHA; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell adhesion; KW Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Host-virus interaction; Integrin; Membrane; Metal-binding; KW Polymorphism; Receptor; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 41 FT CHAIN 42 1049 Integrin alpha-5. FT /FTId=PRO_0000016249. FT CHAIN 42 894 Integrin alpha-5 heavy chain. FT /FTId=PRO_0000016250. FT CHAIN 895 1049 Integrin alpha-5 light chain. FT /FTId=PRO_0000016251. FT TOPO_DOM 42 995 Extracellular (Potential). FT TRANSMEM 996 1021 Helical; (Potential). FT TOPO_DOM 1022 1049 Cytoplasmic (Potential). FT REPEAT 43 108 FG-GAP 1. FT REPEAT 128 188 FG-GAP 2. FT REPEAT 192 245 FG-GAP 3. FT REPEAT 259 315 FG-GAP 4. FT REPEAT 316 377 FG-GAP 5. FT REPEAT 378 437 FG-GAP 6. FT REPEAT 441 504 FG-GAP 7. FT CA_BIND 280 288 FT CA_BIND 334 342 FT CA_BIND 401 409 FT CA_BIND 465 473 FT REGION 1021 1028 Interaction with HPS5. FT MOTIF 1024 1028 GFFKR motif. FT METAL 280 280 Calcium 1. FT METAL 282 282 Calcium 1. FT METAL 284 284 Calcium 1. FT METAL 286 286 Calcium 1; via carbonyl oxygen. FT METAL 288 288 Calcium 1. FT METAL 334 334 Calcium 2. FT METAL 336 336 Calcium 2. FT METAL 338 338 Calcium 2. FT METAL 340 340 Calcium 2; via carbonyl oxygen. FT METAL 342 342 Calcium 2. FT METAL 401 401 Calcium 3. FT METAL 403 403 Calcium 3. FT METAL 405 405 Calcium 3. FT METAL 407 407 Calcium 3; via carbonyl oxygen. FT METAL 409 409 Calcium 3. FT METAL 465 465 Calcium 4. FT METAL 467 467 Calcium 4. FT METAL 469 469 Calcium 4. FT METAL 471 471 Calcium 4; via carbonyl oxygen. FT METAL 473 473 Calcium 4. FT BINDING 262 262 Arg of R-G-D substrate. FT BINDING 269 269 Arg of R-G-D substrate. FT CARBOHYD 84 84 N-linked (GlcNAc...). FT CARBOHYD 182 182 N-linked (GlcNAc...). FT CARBOHYD 297 297 N-linked (GlcNAc...). FT CARBOHYD 307 307 N-linked (GlcNAc...). FT CARBOHYD 316 316 N-linked (GlcNAc...). FT CARBOHYD 524 524 N-linked (GlcNAc...) (Potential). FT CARBOHYD 530 530 N-linked (GlcNAc...) (Potential). FT CARBOHYD 593 593 N-linked (GlcNAc...) (Potential). FT CARBOHYD 609 609 N-linked (GlcNAc...). FT CARBOHYD 675 675 N-linked (GlcNAc...). FT CARBOHYD 712 712 N-linked (GlcNAc...) (Potential). FT CARBOHYD 724 724 N-linked (GlcNAc...) (Potential). FT CARBOHYD 771 771 N-linked (GlcNAc...). FT CARBOHYD 773 773 N-linked (GlcNAc...). FT CARBOHYD 868 868 N-linked (GlcNAc...) (Potential). FT DISULFID 99 108 FT DISULFID 156 176 FT DISULFID 192 205 FT DISULFID 513 522 FT DISULFID 528 584 FT DISULFID 645 651 FT DISULFID 718 731 FT DISULFID 869 921 Interchain (between heavy and light FT chains). FT DISULFID 911 916 FT VARIANT 585 585 R -> I (in dbSNP:rs12318746). FT /FTId=VAR_049631. FT CONFLICT 26 26 L -> V (in Ref. 1 and 3). FT CONFLICT 33 33 L -> V (in Ref. 1 and 3). FT STRAND 50 53 FT STRAND 62 67 FT STRAND 69 72 FT STRAND 75 80 FT STRAND 95 102 FT STRAND 109 111 FT STRAND 125 129 FT STRAND 133 136 FT STRAND 144 149 FT STRAND 152 157 FT STRAND 165 167 FT STRAND 175 180 FT TURN 181 184 FT STRAND 185 189 FT STRAND 193 195 FT TURN 199 204 FT STRAND 209 213 FT STRAND 219 223 FT HELIX 226 229 FT STRAND 231 236 FT HELIX 238 244 FT HELIX 265 267 FT STRAND 274 279 FT STRAND 282 286 FT STRAND 288 297 FT STRAND 300 306 FT STRAND 308 310 FT STRAND 313 318 FT STRAND 328 333 FT STRAND 336 340 FT STRAND 342 347 FT STRAND 351 353 FT STRAND 359 361 FT STRAND 364 368 FT STRAND 380 384 FT HELIX 392 394 FT STRAND 395 407 FT STRAND 409 414 FT STRAND 424 428 FT STRAND 440 443 FT STRAND 458 464 FT STRAND 467 470 FT STRAND 474 478 FT HELIX 479 481 FT STRAND 483 487 FT STRAND 492 503 FT STRAND 513 520 FT STRAND 522 532 FT STRAND 534 536 FT STRAND 538 548 FT TURN 549 555 FT STRAND 560 562 FT TURN 563 565 FT STRAND 566 577 FT STRAND 583 591 FT STRAND 604 612 FT STRAND 614 616 FT STRAND 620 622 FT STRAND 634 641 SQ SEQUENCE 1049 AA; 114536 MW; 6B4D558D4F739CBA CRC64; MGSRTPESPL HAVQLRWGPR RRPPLLPLLL LLLPPPPRVG GFNLDAEAPA VLSGPPGSFF GFSVEFYRPG TDGVSVLVGA PKANTSQPGV LQGGAVYLCP WGASPTQCTP IEFDSKGSRL LESSLSSSEG EEPVEYKSLQ WFGATVRAHG SSILACAPLY SWRTEKEPLS DPVGTCYLST DNFTRILEYA PCRSDFSWAA GQGYCQGGFS AEFTKTGRVV LGGPGSYFWQ GQILSATQEQ IAESYYPEYL INLVQGQLQT RQASSIYDDS YLGYSVAVGE FSGDDTEDFV AGVPKGNLTY GYVTILNGSD IRSLYNFSGE QMASYFGYAV AATDVNGDGL DDLLVGAPLL MDRTPDGRPQ EVGRVYVYLQ HPAGIEPTPT LTLTGHDEFG RFGSSLTPLG DLDQDGYNDV AIGAPFGGET QQGVVFVFPG GPGGLGSKPS QVLQPLWAAS HTPDFFGSAL RGGRDLDGNG YPDLIVGSFG VDKAVVYRGR PIVSASASLT IFPAMFNPEE RSCSLEGNPV ACINLSFCLN ASGKHVADSI GFTVELQLDW QKQKGGVRRA LFLASRQATL TQTLLIQNGA REDCREMKIY LRNESEFRDK LSPIHIALNF SLDPQAPVDS HGLRPALHYQ SKSRIEDKAQ ILLDCGEDNI CVPDLQLEVF GEQNHVYLGD KNALNLTFHA QNVGEGGAYE AELRVTAPPE AEYSGLVRHP GNFSSLSCDY FAVNQSRLLV CDLGNPMKAG ASLWGGLRFT VPHLRDTKKT IQFDFQILSK NLNNSQSDVV SFRLSVEAQA QVTLNGVSKP EAVLFPVSDW HPRDQPQKEE DLGPAVHHVY ELINQGPSSI SQGVLELSCP QALEGQQLLY VTRVTGLNCT TNHPINPKGL ELDPEGSLHH QQKREAPSRS SASSGPQILK CPEAECFRLR CELGPLHQQE SQSLQLHFRV WAKTFLQREH QPFSLQCEAV YKALKMPYRI LPRQLPQKER QVATAVQWTK AEGSYGVPLW IIILAILFGL LLLGLLIYIL YKLGFFKRSL PYGTAMEKAQ LKPPATSDA //