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

    Gene ID: 3676, updated on 17-Jun-2024

    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; AllianceGenome:HGNC:6140
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ITGA4 in Genome Data Viewer
    Location:
    2q31.3
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (181457205..181538940)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (181947690..182029083)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (182321932..182403667)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1934 Neighboring gene MPRA-validated peak3959 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16825 Neighboring gene microRNA 4437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16826 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16827 Neighboring gene uncharacterized LOC124907913 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16828 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12156 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16830 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16831 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16832 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16833 Neighboring gene ceramide kinase like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12158 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:182545894-182546470 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:182548197-182548772 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

    EBI GWAS Catalog

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

    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 
    enables cell adhesion molecule binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables cell adhesion molecule binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables coreceptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables fibronectin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables integrin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables integrin binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein antigen binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in B cell differentiation IC
    Inferred by Curator
    more info
    PubMed 
    involved_in axonogenesis involved in innervation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell adhesion mediated by integrin IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell-cell adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell-cell adhesion mediated by integrin IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in cell-matrix adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell-matrix adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell-matrix adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cell-matrix adhesion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cell-matrix adhesion involved in ameboidal cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to amyloid-beta IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in cellular response to cytokine stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in clathrin-dependent extracellular exosome endocytosis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in diapedesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endodermal cell differentiation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in heterotypic cell-cell adhesion IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in heterotypic cell-cell adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in immune response in gut-associated lymphoid tissue NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in integrin-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in integrin-mediated signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in leukocyte cell-cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in leukocyte cell-cell adhesion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in leukocyte tethering or rolling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of vasoconstriction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in neuron projection extension IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of T cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of endothelial cell apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of leukocyte tethering or rolling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of vascular endothelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in receptor clustering IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in substrate adhesion-dependent cell spreading IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in focal adhesion HDA PubMed 
    located_in growth cone IEA
    Inferred from Electronic Annotation
    more info
     
    part_of integrin alpha4-beta1 complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of integrin alpha4-beta1 complex TAS
    Traceable Author Statement
    more info
    PubMed 
    part_of integrin alpha4-beta7 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of integrin alpha4-beta7 complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of integrin complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in membrane HDA PubMed 
    located_in neuronal cell body IEA
    Inferred from Electronic Annotation
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     

    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)

    NEW Try the new Transcript table

    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_050623.2 RefSeqGene

      Range
      5183..86737
      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
      D3DPG4, P13612, Q7Z4L6
      UniProtKB/TrEMBL
      Q59H74
      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_001316312.2NP_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)
      AC020595, 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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      181457205..181538940
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      181947690..182029083
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)