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Protein

Integrin alpha-5

Gene

ITGA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430).5 Publications
(Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human metapneumovirus.1 Publication
(Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human parvovirus B19.1 Publication
(Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei262Arg of R-G-D substrate1
Binding sitei269Arg of R-G-D substrate1
Metal bindingi280Calcium 11
Metal bindingi282Calcium 11
Metal bindingi284Calcium 11
Metal bindingi286Calcium 1; via carbonyl oxygen1
Metal bindingi288Calcium 11
Metal bindingi334Calcium 21
Metal bindingi336Calcium 21
Metal bindingi338Calcium 21
Metal bindingi340Calcium 2; via carbonyl oxygen1
Metal bindingi342Calcium 21
Metal bindingi401Calcium 31
Metal bindingi403Calcium 31
Metal bindingi405Calcium 31
Metal bindingi407Calcium 3; via carbonyl oxygen1
Metal bindingi409Calcium 31
Metal bindingi465Calcium 41
Metal bindingi467Calcium 41
Metal bindingi469Calcium 41
Metal bindingi471Calcium 4; via carbonyl oxygen1
Metal bindingi473Calcium 41

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi280 – 2889
Calcium bindingi334 – 3429
Calcium bindingi401 – 4099
Calcium bindingi465 – 4739

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Integrin, Receptor
Biological processCell adhesion, Host-virus interaction
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1566948 Elastic fibre formation
R-HSA-1566977 Fibronectin matrix formation
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-216083 Integrin cell surface interactions
R-HSA-445144 Signal transduction by L1
R-HSA-8941332 RUNX2 regulates genes involved in cell migration
SignaLinkiP08648
SIGNORiP08648

Names & Taxonomyi

Protein namesi
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:
Gene namesi
Name:ITGA5
Synonyms:FNRA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000161638.10
HGNCiHGNC:6141 ITGA5
MIMi135620 gene
neXtProtiNX_P08648

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini42 – 995ExtracellularSequence analysisAdd BLAST954
Transmembranei996 – 1021HelicalSequence analysisAdd BLAST26
Topological domaini1022 – 1049CytoplasmicSequence analysisAdd BLAST28

Keywords - Cellular componenti

Cell junction, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3678
OpenTargetsiENSG00000161638
PharmGKBiPA29941

Chemistry databases

ChEMBLiCHEMBL3955

Polymorphism and mutation databases

BioMutaiITGA5
DMDMi23831237

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 411 PublicationAdd BLAST41
ChainiPRO_000001624942 – 1049Integrin alpha-5Add BLAST1008
ChainiPRO_000001625042 – 894Integrin alpha-5 heavy chainAdd BLAST853
ChainiPRO_0000016251895 – 1049Integrin alpha-5 light chainAdd BLAST155

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi84N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi99 ↔ 108
Modified residuei127PhosphoserineCombined sources1
Disulfide bondi156 ↔ 176
Glycosylationi182N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi192 ↔ 205
Glycosylationi297N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi307N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi316N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi513 ↔ 522
Glycosylationi524N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi528 ↔ 584
Glycosylationi530N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi593N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi609N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi645 ↔ 651
Glycosylationi675N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi712N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi718 ↔ 731
Glycosylationi724N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi773N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi868N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi869 ↔ 921Interchain (between heavy and light chains)
Disulfide bondi911 ↔ 916

Post-translational modificationi

Proteolytic cleavage by PCSK5 mediates activation of the precursor.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP08648
MaxQBiP08648
PaxDbiP08648
PeptideAtlasiP08648
PRIDEiP08648
ProteomicsDBi52147
TopDownProteomicsiP08648

PTM databases

GlyConnecti1407
283
iPTMnetiP08648
PhosphoSitePlusiP08648
SwissPalmiP08648
UniCarbKBiP08648

Expressioni

Gene expression databases

BgeeiENSG00000161638 Expressed in 222 organ(s), highest expression level in tibial artery
CleanExiHS_ITGA5
ExpressionAtlasiP08648 baseline and differential
GenevisibleiP08648 HS

Organism-specific databases

HPAiCAB009008
HPA002642

Interactioni

Subunit structurei

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 CIB1. ITGA5:ITGB1 interacts with NOV. ITGA5:ITGB1 interacts with FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 interacts with IL1B (PubMed:29030430).9 Publications
(Microbial infection) Integrin ITGA5:ITGB1 interacts with human metapneumovirus fusion protein.1 Publication
(Microbial infection) Integrin ITGA2:ITGB1 interacts with human parvovirus B19 capsid proteins.1 Publication
(Microbial infection) Interacts with HIV-1 Tat.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109884, 37 interactors
ComplexPortaliCPX-1794 Integrin alpha5-beta1 complex
CORUMiP08648
DIPiDIP-40037N
ELMiP08648
IntActiP08648, 25 interactors
MINTiP08648
STRINGi9606.ENSP00000293379

Chemistry databases

BindingDBiP08648

Structurei

Secondary structure

11049
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP08648
SMRiP08648
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati43 – 108FG-GAP 1PROSITE-ProRule annotationAdd BLAST66
Repeati128 – 188FG-GAP 2PROSITE-ProRule annotationAdd BLAST61
Repeati192 – 245FG-GAP 3PROSITE-ProRule annotationAdd BLAST54
Repeati259 – 311FG-GAP 4PROSITE-ProRule annotationAdd BLAST53
Repeati312 – 377FG-GAP 5PROSITE-ProRule annotationAdd BLAST66
Repeati378 – 437FG-GAP 6PROSITE-ProRule annotationAdd BLAST60
Repeati441 – 504FG-GAP 7PROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1021 – 1028Interaction with HPS58

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1024 – 1028GFFKR motif5

Sequence similaritiesi

Belongs to the integrin alpha chain family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3637 Eukaryota
ENOG410XPVZ LUCA
GeneTreeiENSGT00930000150849
HOGENOMiHOG000231603
HOVERGENiHBG006186
InParanoidiP08648
KOiK06484
OMAiDMNGYPD
OrthoDBiEOG091G05Z4
PhylomeDBiP08648
TreeFamiTF105391

Family and domain databases

Gene3Di2.130.10.130, 1 hit
InterProiView protein in InterPro
IPR013517 FG-GAP
IPR013519 Int_alpha_beta-p
IPR000413 Integrin_alpha
IPR013649 Integrin_alpha-2
IPR018184 Integrin_alpha_C_CS
IPR028994 Integrin_alpha_N
IPR032695 Integrin_dom_sf
PfamiView protein in Pfam
PF01839 FG-GAP, 2 hits
PF08441 Integrin_alpha2, 1 hit
PRINTSiPR01185 INTEGRINA
SMARTiView protein in SMART
SM00191 Int_alpha, 5 hits
SUPFAMiSSF69179 SSF69179, 3 hits
PROSITEiView protein in PROSITE
PS51470 FG_GAP, 7 hits
PS00242 INTEGRIN_ALPHA, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P08648-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGSRTPESPL HAVQLRWGPR RRPPLLPLLL LLLPPPPRVG GFNLDAEAPA
60 70 80 90 100
VLSGPPGSFF GFSVEFYRPG TDGVSVLVGA PKANTSQPGV LQGGAVYLCP
110 120 130 140 150
WGASPTQCTP IEFDSKGSRL LESSLSSSEG EEPVEYKSLQ WFGATVRAHG
160 170 180 190 200
SSILACAPLY SWRTEKEPLS DPVGTCYLST DNFTRILEYA PCRSDFSWAA
210 220 230 240 250
GQGYCQGGFS AEFTKTGRVV LGGPGSYFWQ GQILSATQEQ IAESYYPEYL
260 270 280 290 300
INLVQGQLQT RQASSIYDDS YLGYSVAVGE FSGDDTEDFV AGVPKGNLTY
310 320 330 340 350
GYVTILNGSD IRSLYNFSGE QMASYFGYAV AATDVNGDGL DDLLVGAPLL
360 370 380 390 400
MDRTPDGRPQ EVGRVYVYLQ HPAGIEPTPT LTLTGHDEFG RFGSSLTPLG
410 420 430 440 450
DLDQDGYNDV AIGAPFGGET QQGVVFVFPG GPGGLGSKPS QVLQPLWAAS
460 470 480 490 500
HTPDFFGSAL RGGRDLDGNG YPDLIVGSFG VDKAVVYRGR PIVSASASLT
510 520 530 540 550
IFPAMFNPEE RSCSLEGNPV ACINLSFCLN ASGKHVADSI GFTVELQLDW
560 570 580 590 600
QKQKGGVRRA LFLASRQATL TQTLLIQNGA REDCREMKIY LRNESEFRDK
610 620 630 640 650
LSPIHIALNF SLDPQAPVDS HGLRPALHYQ SKSRIEDKAQ ILLDCGEDNI
660 670 680 690 700
CVPDLQLEVF GEQNHVYLGD KNALNLTFHA QNVGEGGAYE AELRVTAPPE
710 720 730 740 750
AEYSGLVRHP GNFSSLSCDY FAVNQSRLLV CDLGNPMKAG ASLWGGLRFT
760 770 780 790 800
VPHLRDTKKT IQFDFQILSK NLNNSQSDVV SFRLSVEAQA QVTLNGVSKP
810 820 830 840 850
EAVLFPVSDW HPRDQPQKEE DLGPAVHHVY ELINQGPSSI SQGVLELSCP
860 870 880 890 900
QALEGQQLLY VTRVTGLNCT TNHPINPKGL ELDPEGSLHH QQKREAPSRS
910 920 930 940 950
SASSGPQILK CPEAECFRLR CELGPLHQQE SQSLQLHFRV WAKTFLQREH
960 970 980 990 1000
QPFSLQCEAV YKALKMPYRI LPRQLPQKER QVATAVQWTK AEGSYGVPLW
1010 1020 1030 1040
IIILAILFGL LLLGLLIYIL YKLGFFKRSL PYGTAMEKAQ LKPPATSDA
Length:1,049
Mass (Da):114,536
Last modified:October 10, 2002 - v2
Checksum:i6B4D558D4F739CBA
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YHL9H0YHL9_HUMAN
Integrin alpha-5
ITGA5
120Annotation score:
H0YIV7H0YIV7_HUMAN
Integrin alpha-5
ITGA5
119Annotation score:
B4E3F4B4E3F4_HUMAN
cDNA FLJ50382, moderately similar t...
ITGA5
137Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26L → V (PubMed:2958481).Curated1
Sequence conflicti26L → V (PubMed:1834647).Curated1
Sequence conflicti33L → V (PubMed:2958481).Curated1
Sequence conflicti33L → V (PubMed:1834647).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049631585R → I. Corresponds to variant dbSNP:rs12318746Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06256 mRNA Translation: CAA29601.1
BC008786 mRNA Translation: AAH08786.1
M13918 mRNA Translation: AAA52467.1 Sequence problems.
CCDSiCCDS8880.1
PIRiA27079
RefSeqiNP_002196.4, NM_002205.4
UniGeneiHs.505654

Genome annotation databases

EnsembliENST00000293379; ENSP00000293379; ENSG00000161638
GeneIDi3678
KEGGihsa:3678
UCSCiuc001sga.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06256 mRNA Translation: CAA29601.1
BC008786 mRNA Translation: AAH08786.1
M13918 mRNA Translation: AAA52467.1 Sequence problems.
CCDSiCCDS8880.1
PIRiA27079
RefSeqiNP_002196.4, NM_002205.4
UniGeneiHs.505654

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3VI3X-ray2.90A/C42-664[»]
3VI4X-ray2.90A/C42-664[»]
4WJKX-ray1.85A42-491[»]
4WK0X-ray1.78A42-491[»]
4WK2X-ray2.50A42-491[»]
4WK4X-ray2.50A42-491[»]
ProteinModelPortaliP08648
SMRiP08648
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109884, 37 interactors
ComplexPortaliCPX-1794 Integrin alpha5-beta1 complex
CORUMiP08648
DIPiDIP-40037N
ELMiP08648
IntActiP08648, 25 interactors
MINTiP08648
STRINGi9606.ENSP00000293379

Chemistry databases

BindingDBiP08648
ChEMBLiCHEMBL3955

PTM databases

GlyConnecti1407
283
iPTMnetiP08648
PhosphoSitePlusiP08648
SwissPalmiP08648
UniCarbKBiP08648

Polymorphism and mutation databases

BioMutaiITGA5
DMDMi23831237

Proteomic databases

EPDiP08648
MaxQBiP08648
PaxDbiP08648
PeptideAtlasiP08648
PRIDEiP08648
ProteomicsDBi52147
TopDownProteomicsiP08648

Protocols and materials databases

DNASUi3678
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293379; ENSP00000293379; ENSG00000161638
GeneIDi3678
KEGGihsa:3678
UCSCiuc001sga.4 human

Organism-specific databases

CTDi3678
DisGeNETi3678
EuPathDBiHostDB:ENSG00000161638.10
GeneCardsiITGA5
HGNCiHGNC:6141 ITGA5
HPAiCAB009008
HPA002642
MIMi135620 gene
neXtProtiNX_P08648
OpenTargetsiENSG00000161638
PharmGKBiPA29941
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3637 Eukaryota
ENOG410XPVZ LUCA
GeneTreeiENSGT00930000150849
HOGENOMiHOG000231603
HOVERGENiHBG006186
InParanoidiP08648
KOiK06484
OMAiDMNGYPD
OrthoDBiEOG091G05Z4
PhylomeDBiP08648
TreeFamiTF105391

Enzyme and pathway databases

ReactomeiR-HSA-1566948 Elastic fibre formation
R-HSA-1566977 Fibronectin matrix formation
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-216083 Integrin cell surface interactions
R-HSA-445144 Signal transduction by L1
R-HSA-8941332 RUNX2 regulates genes involved in cell migration
SignaLinkiP08648
SIGNORiP08648

Miscellaneous databases

ChiTaRSiITGA5 human
GeneWikiiITGA5
GenomeRNAii3678
PROiPR:P08648
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000161638 Expressed in 222 organ(s), highest expression level in tibial artery
CleanExiHS_ITGA5
ExpressionAtlasiP08648 baseline and differential
GenevisibleiP08648 HS

Family and domain databases

Gene3Di2.130.10.130, 1 hit
InterProiView protein in InterPro
IPR013517 FG-GAP
IPR013519 Int_alpha_beta-p
IPR000413 Integrin_alpha
IPR013649 Integrin_alpha-2
IPR018184 Integrin_alpha_C_CS
IPR028994 Integrin_alpha_N
IPR032695 Integrin_dom_sf
PfamiView protein in Pfam
PF01839 FG-GAP, 2 hits
PF08441 Integrin_alpha2, 1 hit
PRINTSiPR01185 INTEGRINA
SMARTiView protein in SMART
SM00191 Int_alpha, 5 hits
SUPFAMiSSF69179 SSF69179, 3 hits
PROSITEiView protein in PROSITE
PS51470 FG_GAP, 7 hits
PS00242 INTEGRIN_ALPHA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiITA5_HUMAN
AccessioniPrimary (citable) accession number: P08648
Secondary accession number(s): Q96HA5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: October 10, 2002
Last modified: November 7, 2018
This is version 210 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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