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

    Gene ID: 3676, updated on 12-Mar-2017
    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; Vega:OTTHUMG00000154212
    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]
    Orthologs
    Location:
    2q31.3
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (181456892..181538928)
    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

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

    Replication interactions

    Interaction Pubs
    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 gp120/41 (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

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystem (from WikiPathways)
      Arrhythmogenic Right Ventricular Cardiomyopathy, organism-specific biosystemAdapted from KEGG: http://www.genome.jp/kegg/pathway/hsa/hsa05412.html
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
      Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
    • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
      Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
      Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
    • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
      Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
    • Dilated cardiomyopathy, organism-specific biosystem (from KEGG)
      Dilated cardiomyopathy, organism-specific biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • Dilated cardiomyopathy, conserved biosystem (from KEGG)
      Dilated cardiomyopathy, conserved biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
    • ECM-receptor interaction, organism-specific biosystem (from KEGG)
      ECM-receptor interaction, organism-specific biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
    • ECM-receptor interaction, conserved biosystem (from KEGG)
      ECM-receptor interaction, conserved biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
    • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
      Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
    • Focal Adhesion, organism-specific biosystem (from WikiPathways)
      Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, organism-specific biosystem (from KEGG)
      Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Focal adhesion, conserved biosystem (from KEGG)
      Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
    • Hematopoietic cell lineage, organism-specific biosystem (from KEGG)
      Hematopoietic cell lineage, organism-specific biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
    • Hematopoietic cell lineage, conserved biosystem (from KEGG)
      Hematopoietic cell lineage, conserved biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
      Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
      Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
    • Integrin cell surface interactions, organism-specific biosystem (from REACTOME)
      Integrin cell surface interactions, organism-specific biosystemThe extracellular matrix (ECM) is a network of macro-molecules that underlies all epithelia and endothelia and that surrounds all connective tissue cells. This matrix provides the mechanical strength...
    • Integrin-mediated Cell Adhesion, organism-specific biosystem (from WikiPathways)
      Integrin-mediated Cell Adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
    • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
      Intestinal immune network for IgA production, organism-specific biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Intestinal immune network for IgA production, conserved biosystem (from KEGG)
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    • Leishmaniasis, organism-specific biosystem (from KEGG)
      Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
    • Leishmaniasis, conserved biosystem (from KEGG)
      Leishmaniasis, conserved biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
    • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
      Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
      Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
      PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
      PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • Paxillin-dependent events mediated by a4b1, organism-specific biosystem (from Pathway Interaction Database)
      Paxillin-dependent events mediated by a4b1, organism-specific biosystem
      Paxillin-dependent events mediated by a4b1
    • Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem (from Pathway Interaction Database)
      Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem
      Paxillin-independent events mediated by a4b1 and a4b7
    • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
      Regulation of actin cytoskeleton, organism-specific biosystem
      Regulation of actin cytoskeleton
    • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
      Regulation of actin cytoskeleton, conserved biosystem
      Regulation of actin cytoskeleton
    • a4b1 and a4b7 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
      a4b1 and a4b7 Integrin signaling, organism-specific biosystem
      a4b1 and a4b7 Integrin signaling
    Products Interactant Other Gene Complex Source Pubs Description

    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 
    Process Evidence Code Pubs
    B cell differentiation IC
    Inferred by Curator
    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 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 IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    import into cell IEA
    Inferred from Electronic Annotation
    more info
     
    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 
    positive regulation of T cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of leukocyte tethering or rolling IEA
    Inferred from Electronic Annotation
    more info
     
    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 surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    focal adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integrin alpha4-beta7 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    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

    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_000885.5NP_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, BC055419, BU689519, DB114726, L12002, X16983
      Consensus CDS
      CCDS42788.1
      UniProtKB/Swiss-Prot
      P13612
      Related
      ENSP00000380227, OTTHUMP00000205320, ENST00000397033, OTTHUMT00000334427
      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, OTTHUMP00000205321, ENST00000339307, OTTHUMT00000334429
      Conserved Domains (1) summary
      smart00191
      Location:48105
      Int_alpha; Integrin alpha (beta-propellor repeats)

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

      Range
      181456892..181538928
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      182327169..182408848
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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