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Reviewed, UniProtKB/Swiss-Prot P13612 (ITA4_HUMAN)

Last modified July 22, 2008. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Integrin alpha-4
Alternative name(s):
    Integrin alpha-IV
    VLA-4
    CD49 antigen-like family member D
    CD_antigen=CD49d
Gene names
Name: ITGA4
Synonyms: CD49D
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1038 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.

Subunit structure

Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan.

Subcellular location

Membrane; Single-pass type I membrane protein.

Domain

The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion.

Post-translational modification

Phosphorylation on Ser-1027 inhibits PXN binding.

Sequence similarities

Belongs to the integrin alpha chain family.

Contains 7 FG-GAP repeats.

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Ontologies

Keywords

   Biological processCell adhesion
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
   LigandCalcium
   Molecular functionIntegrin
Receptor
   PTMGlycoprotein
Phosphoprotein
   Technical termDirect protein sequencing

Gene Ontology (GO)

   Biological processB cell differentiation

Inferred by curator. Source: UniProtKB

leukocyte adhesion

Inferred from direct assay. Source: UniProtKB

   Cellular componentcell surface

Inferred from direct assay. Source: UniProtKB

   Molecular functionidentical protein binding

Inferred from physical interaction. Source: IntAct

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-703044,EBI-703044

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 3939
Chain40 – 1038999Integrin alpha-4

Regions

Topological domain41 – 983943Extracellular Potential
Transmembrane984 – 100724 Potential
Topological domain1008 – 103831Cytoplasmic Potential
Repeat55 – 11763FG-GAP 1
Repeat118 – 19376FG-GAP 2
Repeat194 – 25360FG-GAP 3
Repeat254 – 30653FG-GAP 4
Repeat309 – 36860FG-GAP 5
Repeat371 – 43060FG-GAP 6
Repeat433 – 48553FG-GAP 7
Calcium binding320 – 3289 Potential
Calcium binding383 – 3919 Potential
Calcium binding445 – 4539 Potential
Motif1009 – 10135GFFKR motif

Sites

Site597 – 5982Cleavage

Amino acid modifications

Modified residue10271Phosphoserine
Glycosylation851N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation2351N-linked (GlcNAc...) Potential
Glycosylation4861N-linked (GlcNAc...) Potential
Glycosylation5241N-linked (GlcNAc...) Potential
Glycosylation5441N-linked (GlcNAc...) Potential
Glycosylation6321N-linked (GlcNAc...) Potential
Glycosylation6511N-linked (GlcNAc...) Potential
Glycosylation6661N-linked (GlcNAc...) Potential
Glycosylation8121N-linked (GlcNAc...) Potential
Glycosylation8271N-linked (GlcNAc...) Potential
Disulfide bond97 ↔ 107 By similarity
Disulfide bond150 ↔ 171 By similarity
Disulfide bond189 ↔ 204 By similarity
Disulfide bond492 ↔ 501 By similarity
Disulfide bond507 ↔ 563 By similarity
Disulfide bond628 ↔ 633 By similarity
Disulfide bond704 ↔ 717 By similarity
Disulfide bond858 ↔ 896 By similarity
Disulfide bond903 ↔ 908 By similarity

Natural variations

Natural variant8841R → Q

Experimental info

Mutagenesis5961K → Q: Abolishes almost completely cleavage
Mutagenesis5971R → L: Abolishes completely cleavage
Mutagenesis10271S → A: Abolishes phosphorylation
Mutagenesis10271S → D: Reduces PXN binding
Mutagenesis10301Y → A: Disrupts PXN binding

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Sequences

Sequence LengthMass (Da)Tools
P13612-1 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: ED7D9075FAEB8996

FASTA1,038115,333
        10         20         30         40         50         60 
MFPTESAWLG KRGANPGPEA AVRETVMLLL CLGVPTGRPY NVDTESALLY QGPHNTLFGY 

        70         80         90        100        110        120 
SVVLHSHGAN RWLLVGAPTA NWLANASVIN PGAIYRCRIG KNPGQTCEQL QLGSPNGEPC 

       130        140        150        160        170        180 
GKTCLEERDN QWLGVTLSRQ PGENGSIVTC GHRWKNIFYI KNENKLPTGG CYGVPPDLRT 

       190        200        210        220        230        240 
ELSKRIAPCY QDYVKKFGEN FASCQAGISS FYTKDLIVMG APGSSYWTGS LFVYNITTNK 

       250        260        270        280        290        300 
YKAFLDKQNQ VKFGSYLGYS VGAGHFRSQH TTEVVGGAPQ HEQIGKAYIF SIDEKELNIL 

       310        320        330        340        350        360 
HEMKGKKLGS YFGASVCAVD LNADGFSDLL VGAPMQSTIR EEGRVFVYIN SGSGAVMNAM 

       370        380        390        400        410        420 
ETNLVGSDKY AARFGESIVN LGDIDNDGFE DVAIGAPQED DLQGAIYIYN GRADGISSTF 

       430        440        450        460        470        480 
SQRIEGLQIS KSLSMFGQSI SGQIDADNNG YVDVAVGAFR SDSAVLLRTR PVVIVDASLS 

       490        500        510        520        530        540 
HPESVNRTKF DCVENGWPSV CIDLTLCFSY KGKEVPGYIV LFYNMSLDVN RKAESPPRFY 

       550        560        570        580        590        600 
FSSNGTSDVI TGSIQVSSRE ANCRTHQAFM RKDVRDILTP IQIEAAYHLG PHVISKRSTE 

       610        620        630        640        650        660 
EFPPLQPILQ QKKEKDIMKK TINFARFCAH ENCSADLQVS AKIGFLKPHE NKTYLAVGSM 

       670        680        690        700        710        720 
KTLMLNVSLF NAGDDAYETT LHVKLPVGLY FIKILELEEK QINCEVTDNS GVVQLDCSIG 

       730        740        750        760        770        780 
YIYVDHLSRI DISFLLDVSS LSRAEEDLSI TVHATCENEE EMDNLKHSRV TVAIPLKYEV 

       790        800        810        820        830        840 
KLTVHGFVNP TSFVYGSNDE NEPETCMVEK MNLTFHVINT GNSMAPNVSV EIMVPNSFSP 

       850        860        870        880        890        900 
QTDKLFNILD VQTTTGECHF ENYQRVCALE QQKSAMQTLK GIVRFLSKTD KRLLYCIKAD 

       910        920        930        940        950        960 
PHCLNFLCNF GKMESGKEAS VHIQLEGRPS ILEMDETSAL KFEIRATGFP EPNPRVIELN 

       970        980        990       1000       1010       1020 
KDENVAHVLL EGLHHQRPKR YFTIVIISSS LLLGLIVLLL ISYVMWKAGF FKRQYKSILQ 

      1030 
EENRRDSWSY INSKSNDD

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References

[1]"The primary structure of the alpha 4 subunit of VLA-4: homology to other integrins and a possible cell-cell adhesion function."
Takada Y., Elices M.J., Crouse C., Hemler M.E.
EMBO J. 8:1361-1368(1989) [PubMed: 2788572] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A single mRNA encodes the alpha 150 and alpha 80/70 forms of the alpha subunit of VLA4."
Rubio M., Nueda A., Vara A., Corbi-Lopez A.L.
Eur. J. Immunol. 22:1099-1102(1992) [PubMed: 1551405] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Identification of two variants of the human integrin alpha 4 subunit."
Szabo M.C., McIntyre B.W.
Mol. Immunol. 32:1453-1454(1995) [PubMed: 8643114] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-884.
[4]"Characterization of the alpha 4 integrin gene promoter."
Rosen G.D., Birkenmeier T.M., Dean D.C.
Proc. Natl. Acad. Sci. U.S.A. 88:4094-4098(1991) [PubMed: 2034655] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-93.
[5]"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 40-53.
[6]"Functional and structural analysis of VLA-4 integrin alpha 4 subunit cleavage."
Teixido J., Parker C.M., Kassner P.D., Hemler M.E.
J. Biol. Chem. 267:1786-1791(1992) [PubMed: 1730718] [Abstract]
Cited for: PROTEIN SEQUENCE OF 598-607, PROTEOLYTIC PROCESSING, MUTAGENESIS OF LYS-596 AND ARG-597.
[7]"A role of chondroitin sulfate glycosaminoglycan binding site in alpha4beta1 integrin-mediated melanoma cell adhesion."
Iida J., Meijne A.M.L., Oegema T.R. Jr., Yednock T.A., Kovach N.L., Furcht L.T., McCarthy J.B.
J. Biol. Chem. 273:5955-5962(1998) [PubMed: 9488735] [Abstract]
Cited for: DOMAIN, INTERACTION WITH CSPG4.
[8]"Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses."
Liu S., Thomas S.M., Woodside D.G., Rose D.M., Kiosses W.B., Pfaff M., Ginsberg M.H.
Nature 402:676-681(1999) [PubMed: 10604475] [Abstract]
Cited for: INTERACTION WITH PXN; LPXN AND TGFB1I1, MUTAGENESIS OF TYR-1030.
[9]"Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin binding."
Han J., Liu S., Rose D.M., Schlaepfer D.D., McDonald H., Ginsberg M.H.
J. Biol. Chem. 276:40903-40909(2001) [PubMed: 11533025] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1027, MUTAGENESIS OF SER-1027.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X16983 mRNA. Translation: CAA34852.1.
L12002 mRNA. Translation: AAB59613.1.
PIRS06046.
RefSeqNP_000876.3.
UniGeneHs.694732

3D structure databases

HSSPHSSP built from PDB template 1A8X based on UniProtKB P11215.
ModBaseSearch...

Protein-protein interaction databases

IntActP13612.

PTM databases

PhosphoSiteP13612.

Genome annotation databases

EnsemblENSG00000115232. Homo sapiens. [Contig view]
GeneID3676.
KEGGhsa:3676.

Organism-specific databases

H-InvDBHIX0023984.
HGNCHGNC:6140. ITGA4.
MIM192975. gene.
PharmGKBPA29940.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMP13612.
HOVERGENP13612.

Enzyme and pathway databases

ReactomeREACT_6900. Signaling in Immune System.

Gene expression databases

ArrayExpressP13612.
CleanExHS_ITGA4.
GermOnlineENSG00000115232. Homo sapiens.

Family and domain databases

InterProIPR013517. FG-GAP.
IPR013519. Int_alpha_beta-p.
IPR000413. Integrin_alpha.
IPR013649. Integrin_alpha-2.
IPR013513. Integrin_alpha_C.
[Graphical view]
PfamPF01839. FG-GAP. 2 hits.
PF00357. Integrin_alpha. 1 hit.
PF08441. Integrin_alpha2. 1 hit.
[Graphical view]
PRINTSPR01185. INTEGRINA.
SMARTSM00191. Int_alpha. 5 hits.
[Graphical view]
PROSITEPS00242. INTEGRIN_ALPHA. 1 hit.
[Graphical view]
ProDomP13612.
[Graphical view] [Entries sharing at least one domain]
BLOCKSSearch...

Other Resources

DrugBankDB00108. Natalizumab.
SOURCESearch...
ProtoNetSearch...

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Entry information

Entry nameITA4_HUMAN
AccessionPrimary (citable) accession number: P13612
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 22, 2008
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human cell differentiation molecules

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

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents