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P08648 (ITA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Integrin alpha-5
Alternative name(s):
CD49 antigen-like family member E
Fibronectin receptor subunit alpha
Integrin alpha-F
VLA-5
CD_antigen=CD49e
Gene names
Name:ITGA5
Synonyms:FNRA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1049 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Integrin alpha-5/beta-1 is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

Subunit structure

Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-5 associates with beta-1. Interacts with HPS5 and NISCH. Interacts with RAB21 and COMP. Interacts with HIV-1 Tat. Interacts with CIB1. Ref.7 Ref.8 Ref.10 Ref.11 Ref.16 Ref.17

Subcellular location

Membrane; Single-pass type I membrane protein.

Post-translational modification

Proteolytic cleavage by PCSK5 mediates activation of the precursor.

Sequence similarities

Belongs to the integrin alpha chain family.

Contains 7 FG-GAP repeats.

Ontologies

Keywords
   Biological processCell adhesion
Host-virus interaction
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   Molecular functionIntegrin
Receptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Traceable author statement PubMed 19267251. Source: BHF-UCL

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cell adhesion

Traceable author statement PubMed 2454952. Source: ProtInc

cell-cell adhesion mediated by integrin

Inferred from electronic annotation. Source: Ensembl

cell-substrate junction assembly

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Traceable author statement. Source: Reactome

heterophilic cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

integrin-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

leukocyte migration

Traceable author statement. Source: Reactome

memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of anoikis

Inferred from mutant phenotype PubMed 15006356. Source: UniProtKB

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell-substrate adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype PubMed 10022831. Source: BHF-UCL

positive regulation of vascular endothelial growth factor receptor signaling pathway

Traceable author statement PubMed 19267251. Source: BHF-UCL

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

wound healing, spreading of epidermal cells

Inferred from expression pattern PubMed 14970227. Source: BHF-UCL

   Cellular_componentalphav-beta3 integrin-vitronectin complex

Traceable author statement PubMed 19267251. Source: BHF-UCL

cytoplasm

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integrin complex

Traceable author statement PubMed 2454952. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

ruffle

Traceable author statement PubMed 11919189. Source: HGNC

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

platelet-derived growth factor receptor binding

Traceable author statement PubMed 19267251. Source: BHF-UCL

vascular endothelial growth factor receptor 2 binding

Traceable author statement PubMed 19267251. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4141 Ref.6
Chain42 – 10491008Integrin alpha-5
PRO_0000016249
Chain42 – 894853Integrin alpha-5 heavy chain
PRO_0000016250
Chain895 – 1049155Integrin alpha-5 light chain
PRO_0000016251

Regions

Topological domain42 – 995954Extracellular Potential
Transmembrane996 – 102126Helical; Potential
Topological domain1022 – 104928Cytoplasmic Potential
Repeat43 – 10866FG-GAP 1
Repeat128 – 18861FG-GAP 2
Repeat192 – 24554FG-GAP 3
Repeat259 – 31557FG-GAP 4
Repeat316 – 37762FG-GAP 5
Repeat378 – 43760FG-GAP 6
Repeat441 – 50464FG-GAP 7
Calcium binding280 – 2889 Ref.17
Calcium binding334 – 3429 Ref.17
Calcium binding401 – 4099 Ref.17
Calcium binding465 – 4739 Ref.17
Region1021 – 10288Interaction with HPS5
Motif1024 – 10285GFFKR motif

Sites

Metal binding2801Calcium 1
Metal binding2821Calcium 1
Metal binding2841Calcium 1
Metal binding2861Calcium 1; via carbonyl oxygen
Metal binding2881Calcium 1
Metal binding3341Calcium 2
Metal binding3361Calcium 2
Metal binding3381Calcium 2
Metal binding3401Calcium 2; via carbonyl oxygen
Metal binding3421Calcium 2
Metal binding4011Calcium 3
Metal binding4031Calcium 3
Metal binding4051Calcium 3
Metal binding4071Calcium 3; via carbonyl oxygen
Metal binding4091Calcium 3
Metal binding4651Calcium 4
Metal binding4671Calcium 4
Metal binding4691Calcium 4
Metal binding4711Calcium 4; via carbonyl oxygen
Metal binding4731Calcium 4
Binding site2621Arg of R-G-D substrate
Binding site2691Arg of R-G-D substrate

Amino acid modifications

Glycosylation841N-linked (GlcNAc...) Ref.17
Glycosylation1821N-linked (GlcNAc...) Ref.17
Glycosylation2971N-linked (GlcNAc...) Ref.12 Ref.13 Ref.17
Glycosylation3071N-linked (GlcNAc...) Ref.12 Ref.13 Ref.17
Glycosylation3161N-linked (GlcNAc...) Ref.17
Glycosylation5241N-linked (GlcNAc...) Potential
Glycosylation5301N-linked (GlcNAc...) Potential
Glycosylation5931N-linked (GlcNAc...) Potential
Glycosylation6091N-linked (GlcNAc...) Ref.17
Glycosylation6751N-linked (GlcNAc...) Ref.12
Glycosylation7121N-linked (GlcNAc...) Potential
Glycosylation7241N-linked (GlcNAc...) Potential
Glycosylation7711N-linked (GlcNAc...); atypical Ref.13
Glycosylation7731N-linked (GlcNAc...) Ref.12 Ref.13
Glycosylation8681N-linked (GlcNAc...) Potential
Disulfide bond99 ↔ 108 Ref.9 Ref.17
Disulfide bond156 ↔ 176 Ref.9 Ref.17
Disulfide bond192 ↔ 205 Ref.9 Ref.17
Disulfide bond513 ↔ 522 Ref.9 Ref.17
Disulfide bond528 ↔ 584 Ref.9 Ref.17
Disulfide bond645 ↔ 651 Ref.9 Ref.17
Disulfide bond718 ↔ 731 Ref.9 Ref.17
Disulfide bond869 ↔ 921Interchain (between heavy and light chains) Ref.9 Ref.17
Disulfide bond911 ↔ 916 Ref.9 Ref.17

Natural variations

Natural variant5851R → I.
Corresponds to variant rs12318746 [ dbSNP | Ensembl ].
VAR_049631

Experimental info

Sequence conflict261L → V Ref.1
Sequence conflict261L → V Ref.3
Sequence conflict331L → V Ref.1
Sequence conflict331L → V Ref.3

Secondary structure

................................................................................................................ 1049
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08648 [UniParc].

Last modified October 10, 2002. Version 2.
Checksum: 6B4D558D4F739CBA

FASTA1,049114,536
        10         20         30         40         50         60 
MGSRTPESPL HAVQLRWGPR RRPPLLPLLL LLLPPPPRVG GFNLDAEAPA VLSGPPGSFF 

        70         80         90        100        110        120 
GFSVEFYRPG TDGVSVLVGA PKANTSQPGV LQGGAVYLCP WGASPTQCTP IEFDSKGSRL 

       130        140        150        160        170        180 
LESSLSSSEG EEPVEYKSLQ WFGATVRAHG SSILACAPLY SWRTEKEPLS DPVGTCYLST 

       190        200        210        220        230        240 
DNFTRILEYA PCRSDFSWAA GQGYCQGGFS AEFTKTGRVV LGGPGSYFWQ GQILSATQEQ 

       250        260        270        280        290        300 
IAESYYPEYL INLVQGQLQT RQASSIYDDS YLGYSVAVGE FSGDDTEDFV AGVPKGNLTY 

       310        320        330        340        350        360 
GYVTILNGSD IRSLYNFSGE QMASYFGYAV AATDVNGDGL DDLLVGAPLL MDRTPDGRPQ 

       370        380        390        400        410        420 
EVGRVYVYLQ HPAGIEPTPT LTLTGHDEFG RFGSSLTPLG DLDQDGYNDV AIGAPFGGET 

       430        440        450        460        470        480 
QQGVVFVFPG GPGGLGSKPS QVLQPLWAAS HTPDFFGSAL RGGRDLDGNG YPDLIVGSFG 

       490        500        510        520        530        540 
VDKAVVYRGR PIVSASASLT IFPAMFNPEE RSCSLEGNPV ACINLSFCLN ASGKHVADSI 

       550        560        570        580        590        600 
GFTVELQLDW QKQKGGVRRA LFLASRQATL TQTLLIQNGA REDCREMKIY LRNESEFRDK 

       610        620        630        640        650        660 
LSPIHIALNF SLDPQAPVDS HGLRPALHYQ SKSRIEDKAQ ILLDCGEDNI CVPDLQLEVF 

       670        680        690        700        710        720 
GEQNHVYLGD KNALNLTFHA QNVGEGGAYE AELRVTAPPE AEYSGLVRHP GNFSSLSCDY 

       730        740        750        760        770        780 
FAVNQSRLLV CDLGNPMKAG ASLWGGLRFT VPHLRDTKKT IQFDFQILSK NLNNSQSDVV 

       790        800        810        820        830        840 
SFRLSVEAQA QVTLNGVSKP EAVLFPVSDW HPRDQPQKEE DLGPAVHHVY ELINQGPSSI 

       850        860        870        880        890        900 
SQGVLELSCP QALEGQQLLY VTRVTGLNCT TNHPINPKGL ELDPEGSLHH QQKREAPSRS 

       910        920        930        940        950        960 
SASSGPQILK CPEAECFRLR CELGPLHQQE SQSLQLHFRV WAKTFLQREH QPFSLQCEAV 

       970        980        990       1000       1010       1020 
YKALKMPYRI LPRQLPQKER QVATAVQWTK AEGSYGVPLW IIILAILFGL LLLGLLIYIL 

      1030       1040 
YKLGFFKRSL PYGTAMEKAQ LKPPATSDA 

« Hide

References

« Hide 'large scale' references
[1]"Amino acid sequence of the human fibronectin receptor."
Argraves W.S., Suzuki S., Arai H., Thompson K., Pierschbacher M.D., Ruoslahti E.
J. Cell Biol. 105:1183-1190(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
Tissue: Placenta.
[3]"The alpha 5 beta 1 fibronectin receptor. Characterization of the alpha 5 gene promoter."
Birkenmeier T.M., McQuillan J.J., Boedeker E.D., Argraves W.S., Ruoslahti E., Dean D.C.
J. Biol. Chem. 266:20544-20549(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-73.
[4]"Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb."
Fitzgerald L.A., Poncz M., Steiner B., Rall S.C., Bennett J.S., Phillips D.R.
Biochemistry 26:8158-8165(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-1049.
[5]"cDNA sequences from the alpha subunit of the fibronectin receptor predict a transmembrane domain and a short cytoplasmic peptide."
Argraves W.S., Pytela R., Suzuki S., Millan J.L., Pierschbacher M.D., Ruoslahti E.
J. Biol. Chem. 261:12922-12924(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 821-1049.
[6]"The very late antigen family of heterodimers is part of a superfamily of molecules involved in adhesion and embryogenesis."
Takada Y., Strominger J.L., Hemler M.E.
Proc. Natl. Acad. Sci. U.S.A. 84:3239-3243(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 42-55.
[7]"The Tat protein of human immunodeficiency virus type-1 promotes vascular cell growth and locomotion by engaging the alpha5beta1 and alphavbeta3 integrins and by mobilizing sequestered basic fibroblast growth factor."
Barillari G., Sgadari C., Fiorelli V., Samaniego F., Colombini S., Manzari V., Modesti A., Nair B.C., Cafaro A., Stuerzl M., Ensoli B.
Blood 94:663-672(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT.
[8]"Insulin receptor substrate 4 associates with the protein IRAS."
Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.
J. Biol. Chem. 277:19439-19447(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NISCH.
[9]"Mass spectrometric based mapping of the disulfide bonding patterns of integrin alpha chains."
Krokhin O.V., Cheng K., Sousa S.L., Ens W., Standing K.G., Wilkins J.A.
Biochemistry 42:12950-12959(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[10]"Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins."
Chen F.-H., Thomas A.O., Hecht J.T., Goldring M.B., Lawler J.
J. Biol. Chem. 280:32655-32661(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COMP.
[11]"Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins."
Pellinen T., Arjonen A., Vuoriluoto K., Kallio K., Fransen J.A.M., Ivaska J.
J. Cell Biol. 173:767-780(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB21.
[12]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-675 AND ASN-773.
Tissue: Liver.
[13]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-771 AND ASN-773.
Tissue: Leukemic T-cell.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Cleavage of endometrial alpha-integrins into their functional forms is mediated by proprotein convertase 5/6."
Paule S., Aljofan M., Simon C., Rombauts L.J., Nie G.
Hum. Reprod. 27:2766-2774(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC CLEAVAGE BY PCSK5.
[16]"Identification of novel integrin binding partners for calcium and integrin binding protein 1 (CIB1): structural and thermodynamic basis of CIB1 promiscuity."
Freeman T.C. Jr., Black J.L., Bray H.G., Dagliyan O., Wu Y.I., Tripathy A., Dokholyan N.V., Leisner T.M., Parise L.V.
Biochemistry 52:7082-7090(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CIB1.
[17]"Crystal structure of alpha5beta1 integrin ectodomain: atomic details of the fibronectin receptor."
Nagae M., Re S., Mihara E., Nogi T., Sugita Y., Takagi J.
J. Cell Biol. 197:131-140(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 42-664 IN COMPLEX WITH ANTIBODY; ITGB1 AND RGD PEPTIDE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-84; ASN-182; ASN-297; ASN-307; ASN-316 AND ASN-609, SUBSTRATE-BINDING SITES, CALCIUM-BINDING SITES, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06256 mRNA. Translation: CAA29601.1.
BC008786 mRNA. Translation: AAH08786.1.
M13918 mRNA. Translation: AAA52467.1. Sequence problems.
PIRA27079.
RefSeqNP_002196.2. NM_002205.2.
UniGeneHs.505654.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3VI3X-ray2.90A/C42-664[»]
3VI4X-ray2.90A/C42-664[»]
ProteinModelPortalP08648.
SMRP08648. Positions 42-1035.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109884. 21 interactions.
DIPDIP-40037N.
IntActP08648. 16 interactions.
MINTMINT-5005934.
STRING9606.ENSP00000293379.

Chemistry

BindingDBP08648.
ChEMBLCHEMBL3955.

PTM databases

PhosphoSiteP08648.
UniCarbKBP08648.

Polymorphism databases

DMDM23831237.

Proteomic databases

PaxDbP08648.
PeptideAtlasP08648.
PRIDEP08648.

Protocols and materials databases

DNASU3678.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293379; ENSP00000293379; ENSG00000161638.
GeneID3678.
KEGGhsa:3678.
UCSCuc001sga.3. human.

Organism-specific databases

CTD3678.
GeneCardsGC12M054789.
HGNCHGNC:6141. ITGA5.
HPACAB009008.
HPA002642.
MIM135620. gene.
neXtProtNX_P08648.
PharmGKBPA29941.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG26407.
HOGENOMHOG000231603.
HOVERGENHBG006186.
InParanoidP08648.
KOK06484.
OMAERSCSLE.
OrthoDBEOG7HQN77.
PhylomeDBP08648.
TreeFamTF105391.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_118779. Extracellular matrix organization.
REACT_604. Hemostasis.
SignaLinkP08648.

Gene expression databases

ArrayExpressP08648.
BgeeP08648.
CleanExHS_ITGA5.
GenevestigatorP08648.

Family and domain databases

InterProIPR013517. FG-GAP.
IPR013519. Int_alpha_beta-p.
IPR000413. Integrin_alpha.
IPR013649. Integrin_alpha-2.
IPR018184. Integrin_alpha_C_CS.
[Graphical view]
PfamPF01839. FG-GAP. 3 hits.
PF08441. Integrin_alpha2. 1 hit.
[Graphical view]
PRINTSPR01185. INTEGRINA.
SMARTSM00191. Int_alpha. 5 hits.
[Graphical view]
PROSITEPS51470. FG_GAP. 7 hits.
PS00242. INTEGRIN_ALPHA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiITGA5.
GenomeRNAi3678.
NextBio14395.
PROP08648.
SOURCESearch...

Entry information

Entry nameITA5_HUMAN
AccessionPrimary (citable) accession number: P08648
Secondary accession number(s): Q96HA5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 10, 2002
Last modified: April 16, 2014
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries