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Q00651 (ITA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Integrin alpha-4
Alternative name(s):
CD49 antigen-like family member D
Integrin alpha-IV
Lymphocyte Peyer patch adhesion molecules subunit alpha
Short name=LPAM subunit alpha
VLA-4 subunit alpha
CD_antigen=CD49d
Gene names
Name:Itga4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1039 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Integrins alpha-4/beta-1 (VLA-4 or LPAM-2) and alpha-4/beta-7 (LPAM-1) 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. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. Mice homozygous for a null mutation of the alpha-4 subunit gene die by day E11-E14 from detachment and rupture of the epicardium and coronary arteries.

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. Interacts with AMICA1; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling AMICA1 homodimerization By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Peyer patch homing cells.

Domain

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

Post-translational modification

Phosphorylation on Ser-1028 inhibits PXN binding By similarity.

Sequence similarities

Belongs to the integrin alpha chain family.

Contains 7 FG-GAP repeats.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentMembrane
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   Molecular functionIntegrin
Receptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell migration

Inferred from mutant phenotype PubMed 23661644. Source: MGI

blood vessel remodeling

Inferred from mutant phenotype PubMed 16529735. Source: MGI

cell adhesion

Inferred from mutant phenotype PubMed 12021259. Source: MGI

cell migration

Inferred from mutant phenotype PubMed 12021259PubMed 16529735. Source: MGI

cell-matrix adhesion

Traceable author statement PubMed 20299672. Source: DFLAT

chorio-allantoic fusion

Inferred from mutant phenotype PubMed 7539359. Source: MGI

face development

Inferred from mutant phenotype PubMed 7539359. Source: MGI

heart development

Inferred from mutant phenotype PubMed 12021259PubMed 7539359. Source: MGI

heterophilic cell-cell adhesion

Inferred from mutant phenotype PubMed 8145052. Source: MGI

integrin-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte cell-cell adhesion

Inferred from mutant phenotype PubMed 8562500. Source: MGI

mesenchyme development

Traceable author statement PubMed 20299672. Source: DFLAT

negative regulation of protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

single organismal cell-cell adhesion

Traceable author statement PubMed 20299672. Source: DFLAT

visceral serous pericardium development

Traceable author statement PubMed 20299672. Source: DFLAT

   Cellular_componentcell surface

Traceable author statement PubMed 20299672. Source: DFLAT

cell-cell junction

Inferred from direct assay PubMed 23610556. Source: MGI

external side of plasma membrane

Inferred from direct assay PubMed 7539359PubMed 8557754. Source: MGI

integrin complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionfibronectin binding

Inferred from mutant phenotype PubMed 8145052. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4040 Potential
Chain41 – 1039999Integrin alpha-4
PRO_0000016245

Regions

Topological domain41 – 983943Extracellular Potential
Transmembrane984 – 100724Helical; Potential
Topological domain1008 – 103932Cytoplasmic Potential
Repeat42 – 10766FG-GAP 1
Repeat117 – 18468FG-GAP 2
Repeat193 – 24452FG-GAP 3
Repeat245 – 30056FG-GAP 4
Repeat301 – 35858FG-GAP 5
Repeat362 – 41958FG-GAP 6
Repeat423 – 48563FG-GAP 7
Calcium binding321 – 3299 Potential
Calcium binding384 – 3929 Potential
Calcium binding446 – 4549 Potential
Motif613 – 62311SG1
Motif1010 – 10145GFFKR motif

Sites

Site598 – 5992Cleavage

Amino acid modifications

Modified residue10281Phosphoserine Ref.2
Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation2361N-linked (GlcNAc...) Potential
Glycosylation4871N-linked (GlcNAc...) Potential
Glycosylation5251N-linked (GlcNAc...) Potential
Glycosylation5451N-linked (GlcNAc...) Potential
Glycosylation6331N-linked (GlcNAc...) Potential
Glycosylation6521N-linked (GlcNAc...) Potential
Glycosylation6671N-linked (GlcNAc...) Potential
Glycosylation8131N-linked (GlcNAc...) Potential
Glycosylation8281N-linked (GlcNAc...) Potential
Disulfide bond98 ↔ 108 By similarity
Disulfide bond151 ↔ 172 By similarity
Disulfide bond190 ↔ 205 By similarity
Disulfide bond493 ↔ 502 By similarity
Disulfide bond508 ↔ 564 By similarity
Disulfide bond629 ↔ 634 By similarity
Disulfide bond705 ↔ 718 By similarity
Disulfide bond859 ↔ 897 By similarity
Disulfide bond904 ↔ 909 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q00651 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: C8C0BC611F7E9847

FASTA1,039115,696
        10         20         30         40         50         60 
MFSTKSAWLR NGGADQGPRG IALREAVMLL LYFGVPTGPS YNLDPENALL YQGPSGTLFG 

        70         80         90        100        110        120 
YSVVLHSHGS KRWLIVGAPT ASWLSNASVV NPGAIYRCGI RKNPNQTCEQ LQSGSPSGEP 

       130        140        150        160        170        180 
CGKTCLEERD NQWLGVTLSR QPGENGSIVT CGHRWKNIFY MKSDNKLPTG ICYVMPSDLR 

       190        200        210        220        230        240 
TELSKRMAPC YKDYTRKFGE NFASCQAGIS SFYTQDLIVM GAPGSSYWTG TVFVYNITTN 

       250        260        270        280        290        300 
QYKAFVDRQN QVKFGSYLGY SVGAGHFRSP HTTEVVGGAP QHEQIGKAYI FSIDENELNI 

       310        320        330        340        350        360 
VYEMKGKKLG SYFGASVCAV DLNADGFSDL LVGAPMQSTI REEGRVFVYI NSGMGAVMVE 

       370        380        390        400        410        420 
MERVLVGSDK YAARFGESIA NLGDIDNDGF EDIAIGAPQE DDLRGAVYIY NGRVDGISST 

       430        440        450        460        470        480 
YSQRIEGQQI SKSLRMFGQS ISGQIDADNN GYVDVAVGAF QSDSAVLLRT RPVVIVEASL 

       490        500        510        520        530        540 
SHPESVNRTK FDCTENGLPS VCMHLTLCFS YKGKEVPGYI VLFYNVSLDV HRKAESPSRF 

       550        560        570        580        590        600 
YFFSNGTSDV ITGSIRVSSS GEKCRTHQAF MRKDVRDILT PIHVEATYHL GHHVITKRNT 

       610        620        630        640        650        660 
EEFPPLQPIL QQKKEKDVIR KMINFARFCA YENCSADLQV SAKVGFLKPY ENKTYLAVGS 

       670        680        690        700        710        720 
MKTIMLNVSL FNAGDDAYET TLNVQLPTGL YFIKILDLEE KQINCEVTES SGIVKLACSL 

       730        740        750        760        770        780 
GYIYVDRLSR IDISFLLDVS SLSRAHEDLS ISVHASCENE GELDQVRDNR VTLTIPLRYE 

       790        800        810        820        830        840 
VMLTVHGLVN PTSFVYGSSE ENEPETCMAE KLNLTFHVIN TGISMAPNVS VKIMVPNSFL 

       850        860        870        880        890        900 
PQDDKLFNVL DVQTTTGQCH FKHYGRECTF AQQKGIAGTL TDIVKFLSKT DKRLLYCMKA 

       910        920        930        940        950        960 
DQHCLDFLCN FGKMESGKEA SVHIQLEGRP SILEMDETSS LKFEIKATAF PEPHPKVIEL 

       970        980        990       1000       1010       1020 
NKDENVAHVF LEGLHHQRPK RHFTIIIITI SLLLGLIVLL LISCVMWKAG FFKRQYKSIL 

      1030 
QEENRRDSWS YVNSKSNDD 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of cDNAs for the alpha subunit of the murine lymphocyte-Peyer's patch adhesion molecule."
Neuhaus H., Hu M.C.-T., Hemler M.E., Takada Y., Holzmann B., Weissman I.L.
J. Cell Biol. 115:1149-1158(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1028, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X53176 mRNA. Translation: CAA37316.1.
PIRA41131.
RefSeqNP_034706.3. NM_010576.3.
UniGeneMm.31903.

3D structure databases

ProteinModelPortalQ00651.
SMRQ00651. Positions 41-836, 983-1022.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL2111481.

PTM databases

PhosphoSiteQ00651.

Proteomic databases

MaxQBQ00651.
PaxDbQ00651.
PRIDEQ00651.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID16401.
KEGGmmu:16401.

Organism-specific databases

CTD3676.
MGIMGI:96603. Itga4.

Phylogenomic databases

eggNOGNOG324320.
HOGENOMHOG000088626.
HOVERGENHBG004538.
InParanoidQ00651.
KOK06483.
PhylomeDBQ00651.

Gene expression databases

CleanExMM_ITGA4.
GenevestigatorQ00651.

Family and domain databases

InterProIPR013519. Int_alpha_beta-p.
IPR000413. Integrin_alpha.
IPR013649. Integrin_alpha-2.
IPR018184. Integrin_alpha_C_CS.
[Graphical view]
PfamPF08441. Integrin_alpha2. 1 hit.
[Graphical view]
PRINTSPR01185. INTEGRINA.
SMARTSM00191. Int_alpha. 6 hits.
[Graphical view]
PROSITEPS51470. FG_GAP. 7 hits.
PS00242. INTEGRIN_ALPHA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSITGA4. mouse.
NextBio289557.
PROQ00651.
SOURCESearch...

Entry information

Entry nameITA4_MOUSE
AccessionPrimary (citable) accession number: Q00651
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot