Format

Send to:

Choose Destination

ITGA4 integrin subunit alpha 4 [ Homo sapiens (human) ]

Gene ID: 3676, updated on 24-Dec-2019

Summary

Official Symbol
ITGA4provided by HGNC
Official Full Name
integrin subunit alpha 4provided by HGNC
Primary source
HGNC:HGNC:6140
See related
Ensembl:ENSG00000115232 MIM:192975
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IA4; CD49D
Summary
The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
Expression
Broad expression in spleen (RPKM 22.7), appendix (RPKM 22.2) and 17 other tissues See more
Orthologs

Genomic context

See ITGA4 in Genome Data Viewer
Location:
2q31.3
Exon count:
29
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (181456892..181538940)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (182321619..182402474)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985831 Neighboring gene long intergenic non-protein coding RNA 1934 Neighboring gene microRNA 4437 Neighboring gene ceramide kinase like Neighboring gene neuronal differentiation 1 Neighboring gene SAP18 pseudogene 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genetic variation associated with circulating monocyte count in the eMERGE Network.
NHGRI GWA Catalog
Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
Multiple loci are associated with white blood cell phenotypes.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 infected patients exhibit an upregulation of ITGA4/ITGB7 positive lymphocytes in peripheral blood of immunological nonresponder clinical samples PubMed
Knockdown of integrin alpha 4 protein by shRNA inhibits HIV-1 infection in primary lymphocytes PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 Env gp120 amino acids from position 158 to 192 bind alpha-4/beta-7 integrin (ITGA4/ITGB7) PubMed
env HIV-1 Env (gp120) V2/V3 loops bind to ITGA4 and ITGB7 (a4b7), which can be inhibited by anti-V2 peptide or integrin or anti-V3 antibodies PubMed
env HIV-1 Env gp120/41 (JRFL Env in the contaxt of HIV-Gag-GFP VLP) binds to ITGA4 on the surface of basophils PubMed
env HIV-1 Env gp120 with P/SDI/V-ITGA4/ITGB7 binding motifs interact more with ITGA4/ITGB7 PubMed
env Increased integrin alpha4beta7 affinity is mediated by sequences encoded in gp120 V1/V2 and also influenced by N-linked glycosylation sites located in gp120 C3/V4 PubMed
env Integrin alpha4beta7 mediates HIV-1 gp120 binding to natural killer cells. The residues 182-184 in the V2 loop of gp120 is required for the binding between gp120 and integrin alpha4beta7 PubMed
env Little or no integrin alpha4beta7 binding is detected with multiple HIV-1 gp120s and gp140s, including gp120s from transmitted/founder strains, or when gp120 is produced in CHO, 293T, and 293S/GnT1(-/-) cells PubMed
env The peptide segment at positions 166-178 of the V2 loop of HIV-1 gp120 appears to harbor a cryptic determinant of integrin alpha4beta7 binding on primary human T cells PubMed
env Treatment of B cells with HIV-1 gp120 upregulates the expression of FCRL4 and limits the proliferative expansion of B cells in an integrin alpha 4/beta 7-dependent manner PubMed
env HIV-1 gp120 binds to human B cells through integrin alpha 4/beta 7 PubMed
env HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed
env The gp120-integrin alpha4beta7 complex mediates LFA-1 activation on T cells and increases the efficiency of infection by promoting synapse formation PubMed
env A mutant integrin alpha4beta7 carrying alpha4 K201/N/I/E reduces its binding to HIV-1 gp120 PubMed
env HIV-1 gp120 is identified to have a physical interaction with integrin, alpha 4 (ITGA4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
env HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules PubMed
Envelope surface glycoprotein gp160, precursor env Little or no integrin alpha4beta7 binding is detected with multiple HIV-1 gp140s in human cells PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC90518

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to C-X3-C chemokine binding IDA
Inferred from Direct Assay
more info
PubMed 
cell adhesion molecule binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell adhesion molecule binding IPI
Inferred from Physical Interaction
more info
PubMed 
coreceptor activity TAS
Traceable Author Statement
more info
PubMed 
fibronectin binding IEA
Inferred from Electronic Annotation
more info
 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein antigen binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
B cell differentiation IC
Inferred by Curator
more info
PubMed 
axonogenesis involved in innervation IEA
Inferred from Electronic Annotation
more info
 
cell-cell adhesion in response to extracellular stimulus IGI
Inferred from Genetic Interaction
more info
PubMed 
cell-cell adhesion mediated by integrin IGI
Inferred from Genetic Interaction
more info
PubMed 
cell-matrix adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell-matrix adhesion involved in ameboidal cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to amyloid-beta IGI
Inferred from Genetic Interaction
more info
PubMed 
cellular response to cytokine stimulus IEA
Inferred from Electronic Annotation
more info
 
clathrin-dependent extracellular exosome endocytosis IEA
Inferred from Electronic Annotation
more info
 
diapedesis IEA
Inferred from Electronic Annotation
more info
 
endodermal cell differentiation IEP
Inferred from Expression Pattern
more info
PubMed 
extracellular matrix organization TAS
Traceable Author Statement
more info
 
heterotypic cell-cell adhesion IGI
Inferred from Genetic Interaction
more info
PubMed 
heterotypic cell-cell adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
integrin-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
leukocyte cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
leukocyte migration TAS
Traceable Author Statement
more info
 
leukocyte tethering or rolling IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
neuron projection extension IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T cell migration IEA
Inferred from Electronic Annotation
more info
 
positive regulation of endothelial cell apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of leukocyte tethering or rolling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of vascular endothelial cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
receptor clustering IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
substrate adhesion-dependent cell spreading IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cell IEA
Inferred from Electronic Annotation
more info
 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
focal adhesion HDA PubMed 
growth cone IEA
Inferred from Electronic Annotation
more info
 
integrin alpha4-beta7 complex IDA
Inferred from Direct Assay
more info
PubMed 
membrane HDA PubMed 
neuronal cell body IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
protein-containing complex TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
integrin alpha-4
Names
269C wild type
CD49 antigen-like family member D
VLA-4 subunit alpha
alpha 4 subunit of VLA-4 receptor
antigen CD49D, alpha-4 subunit of VLA-4 receptor
integrin alpha-IV
very late activation protein 4 receptor, alpha 4 subunit

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_050623.1 RefSeqGene

    Range
    5001..87037
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000885.6NP_000876.3  integrin alpha-4 isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_000876.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC020595
    Consensus CDS
    CCDS42788.1
    UniProtKB/Swiss-Prot
    P13612
    Related
    ENSP00000380227.2, ENST00000397033.7
    Conserved Domains (2) summary
    smart00191
    Location:366418
    Int_alpha; Integrin alpha (beta-propellor repeats)
    pfam08441
    Location:463902
    Integrin_alpha2; Integrin alpha
  2. NM_001316312.1NP_001303241.1  integrin alpha-4 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate 3' terminal exon, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    BC055419, DB114726
    Consensus CDS
    CCDS82540.1
    UniProtKB/Swiss-Prot
    P13612
    Related
    ENSP00000340149.4, ENST00000339307.8
    Conserved Domains (1) summary
    smart00191
    Location:48105
    Int_alpha; Integrin alpha (beta-propellor repeats)

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    181456892..181538940
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Support Center