P08648 (ITA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Cleaved into the following 2 chains:

1. Integrin alpha-5 heavy chain
2. Integrin alpha-5 light chain

Gene names

Name:	ITGA5
Synonyms:	FNRA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1049 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 an 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. Ref.7 Ref.8 Ref.10 Ref.11
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the integrin alpha chain family. Contains 7 FG-GAP repeats.

Ontologies

Keywords
Biological process	Cell adhesion Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Integrin Receptor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Traceable author statement. Source: BHF-UCL axon guidance Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome integrin-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW leukocyte migration Traceable author statement. Source: Reactome positive regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of vascular endothelial growth factor receptor signaling pathway Traceable author statement. Source: BHF-UCL wound healing, spreading of epidermal cells Inferred from expression pattern. Source: BHF-UCL
Cellular component	alphav-beta3 integrin-vitronectin complex Traceable author statement. Source: BHF-UCL integrin complex Traceable author statement. Source: ProtInc ruffle Traceable author statement. Source: HGNC
Molecular function	platelet-derived growth factor receptor binding Traceable author statement. Source: BHF-UCL receptor activity Inferred from electronic annotation. Source: UniProtKB-KW vascular endothelial growth factor receptor 2 binding Traceable author statement. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 41	41	Ref.6
	Chain	42 – 1049	1008	Integrin alpha-5		PRO_0000016249
	Chain	42 – 894	853	Integrin alpha-5 heavy chain		PRO_0000016250
	Chain	895 – 1049	155	Integrin alpha-5 light chain		PRO_0000016251
Regions
	Topological domain	42 – 995	954	Extracellular Potential
	Transmembrane	996 – 1021	26	Helical; Potential
	Topological domain	1022 – 1049	28	Cytoplasmic Potential
	Repeat	43 – 108	66	FG-GAP 1
	Repeat	128 – 188	61	FG-GAP 2
	Repeat	192 – 245	54	FG-GAP 3
	Repeat	259 – 315	57	FG-GAP 4
	Repeat	316 – 377	62	FG-GAP 5
	Repeat	378 – 437	60	FG-GAP 6
	Repeat	441 – 504	64	FG-GAP 7
	Calcium binding	334 – 342	9	Potential
	Calcium binding	401 – 409	9	Potential
	Calcium binding	465 – 473	9	Potential
	Region	1021 – 1028	8	Interaction with HPS5
	Motif	1024 – 1028	5	GFFKR motif
Amino acid modifications
	Glycosylation	84	1	N-linked (GlcNAc...) Potential
	Glycosylation	182	1	N-linked (GlcNAc...) Potential
	Glycosylation	297	1	N-linked (GlcNAc...) Ref.12 Ref.13
	Glycosylation	307	1	N-linked (GlcNAc...) Ref.12 Ref.13
	Glycosylation	316	1	N-linked (GlcNAc...) Potential
	Glycosylation	524	1	N-linked (GlcNAc...) Potential
	Glycosylation	530	1	N-linked (GlcNAc...) Potential
	Glycosylation	593	1	N-linked (GlcNAc...) Potential
	Glycosylation	609	1	N-linked (GlcNAc...) Potential
	Glycosylation	675	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	712	1	N-linked (GlcNAc...) Potential
	Glycosylation	724	1	N-linked (GlcNAc...) Potential
	Glycosylation	771	1	N-linked (GlcNAc...) Ref.13
	Glycosylation	773	1	N-linked (GlcNAc...) Ref.12 Ref.13
	Glycosylation	868	1	N-linked (GlcNAc...) Potential
	Disulfide bond	99 ↔ 108		Ref.9
	Disulfide bond	156 ↔ 176		Ref.9
	Disulfide bond	192 ↔ 205		Ref.9
	Disulfide bond	513 ↔ 522		By similarity
	Disulfide bond	528 ↔ 584		By similarity
	Disulfide bond	645 ↔ 651		Ref.9
	Disulfide bond	718 ↔ 731		Ref.9
	Disulfide bond	869 ↔ 921		Interchain (between heavy and light chains) Ref.9
	Disulfide bond	911 ↔ 916		Ref.9
Natural variations
	Natural variant	585	1	R → I. Corresponds to variant rs12318746 [ dbSNP | Ensembl ].		VAR_049631
Experimental info
	Sequence conflict	26	1	L → V Ref.1
	Sequence conflict	26	1	L → V Ref.3
	Sequence conflict	33	1	L → V Ref.1
	Sequence conflict	33	1	L → V Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P08648 [UniParc]. Last modified October 10, 2002. Version 2. Checksum: 6B4D558D4F739CBA	FASTA	1,049	114,536
	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

References

	« Hide 'large scale' referencesShow '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: 2958481] [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: 15489334] [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: 1834647] [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: 2450560] [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: 2944883] [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: 3033641] [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: 10397733] [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: 11912194] [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: 14596610] [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: 16051604] [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: 16754960] [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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-675 AND ASN-773, MASS SPECTROMETRY. 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: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-297; ASN-307; ASN-771 AND ASN-773, MASS SPECTROMETRY. 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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.
IPI	IPI00306604.
PIR	A27079.
RefSeq	NP_002196.2. NM_002205.2.
UniGene	Hs.505654.
3D structure databases
ProteinModelPortal	P08648.
SMR	P08648. Positions 205-491, 992-1031.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40037N.
IntAct	P08648. 6 interactions.
MINT	MINT-5005934.
STRING	P08648.
PTM databases
GlycoSuiteDB	P08648.
PhosphoSite	P08648.
Polymorphism databases
DMDM	23831237.
Proteomic databases
PeptideAtlas	P08648.
PRIDE	P08648.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000293379; ENSP00000293379; ENSG00000161638.
GeneID	3678.
KEGG	hsa:3678.
UCSC	uc001sga.1. human.
Organism-specific databases
CTD	3678.
GeneCards	GC12M054789.
H-InvDB	HIX0010697.
HGNC	HGNC:6141. ITGA5.
HPA	CAB009008. HPA002642.
MIM	135620. gene.
neXtProt	NX_P08648.
PharmGKB	PA29941.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19732.
GeneTree	ENSGT00560000076661.
HOGENOM	HBG402992.
HOVERGEN	HBG006186.
InParanoid	P08648.
OMA	MKIYLRN.
OrthoDB	EOG43JC3X.
PhylomeDB	P08648.
Enzyme and pathway databases
Pathway_Interaction_DB	angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling. syndecan_2_pathway. Syndecan-2-mediated signaling events. syndecan_4_pathway. Syndecan-4-mediated signaling events. lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P08648.
Bgee	P08648.
CleanEx	HS_ITGA5.
Genevestigator	P08648.
GermOnline	ENSG00000161638. Homo sapiens.
Family and domain databases
InterPro	IPR013517. FG-GAP. IPR013519. Int_alpha_beta-p. IPR000413. Integrin_alpha. IPR013649. Integrin_alpha-2. IPR018184. Integrin_alpha_C_CS. [Graphical view]
KO	K06484.
Pfam	PF01839. FG-GAP. 3 hits. PF08441. Integrin_alpha2. 1 hit. [Graphical view]
PRINTS	PR01185. INTEGRINA.
SMART	SM00191. Int_alpha. 5 hits. [Graphical view]
PROSITE	PS51470. FG_GAP. 7 hits. PS00242. INTEGRIN_ALPHA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	14395.
SOURCE	Search...

Entry information

Entry name

ITA5_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 138 of the entry and version 2 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.