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    MICA MHC class I polypeptide-related sequence A [ Homo sapiens (human) ]

    Gene ID: 100507436, updated on 28-Aug-2015
    Official Symbol
    MICAprovided by HGNC
    Official Full Name
    MHC class I polypeptide-related sequence Aprovided by HGNC
    Primary source
    HGNC:HGNC:7090
    See related
    Ensembl:ENSG00000204520; MIM:600169; Vega:OTTHUMG00000031073
    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
    MIC-A; PERB11.1
    Summary
    This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]
    Orthologs
    See MICA in Epigenomics, MapViewer
    Location:
    6p21.33
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 6 NC_000006.12 (31399784..31415315)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31367561..31383090)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class I, S (pseudogene) Neighboring gene uncharacterized LOC101929072 Neighboring gene uncharacterized LOC105375017 Neighboring gene major histocompatibility complex, class I, X (pseudogene)

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.
    NHGRI GWA Catalog
    A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.
    NHGRI GWA Catalog
    Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
    NHGRI GWA Catalog
    Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
    NHGRI GWA Catalog
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    NHGRI GWA Catalog
    Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
    NHGRI GWA Catalog
    Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma.
    NHGRI GWA Catalog
    Genome-wide association study of susceptibility loci for cervical cancer.
    NHGRI GWA Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    NHGRI GWA Catalog
    Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome-wide association study.
    NHGRI GWA Catalog
    Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.
    NHGRI GWA Catalog
    Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
    NHGRI GWA Catalog
    The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef downregulates cell surface expression of MICA, ULBP1 and ULBP2 in natural killer (NK) cells PubMed

    Go to the HIV-1, Human Interaction Database

    • Allograft Rejection, organism-specific biosystem (from WikiPathways)
      Allograft Rejection, organism-specific biosystemThis pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from the KEGG pathway http://www...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Clone Names

    • FLJ36918, FLJ60820, MGC21250, MGC111087

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NOT beta-2-microglobulin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    natural killer cell lectin-like receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    natural killer cell lectin-like receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    T cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    antigen processing and presentation IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to DNA damage stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytolysis IEA
    Inferred from Electronic Annotation
    more info
     
    defense response to bacterium IDA
    Inferred from Direct Assay
    more info
    PubMed 
    defense response to virus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    gamma-delta T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    immune response to tumor cell IDA
    Inferred from Direct Assay
    more info
    PubMed 
    natural killer cell mediated cytotoxicity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of natural killer cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of natural killer cell mediated cytotoxicity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to heat IDA
    Inferred from Direct Assay
    more info
    PubMed 
    viral process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    MHC class I polypeptide-related sequence A
    Names
    HLA class I antigen
    MHC class I chain-related protein A
    MICA
    stress inducible class I homolog

    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_034139.1 RefSeqGene

      Range
      5001..20630
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000247.2NP_000238.1  MHC class I polypeptide-related sequence A isoform 1 (MICA*001) precursor

      See identical proteins and their annotated locations for NP_000238.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1*001, also known as 1) is derived from the MICA*001 allele. It encodes the longest isoform (1). The MICA*001 allele is found in the c6_QBL (ALT_REF_LOCI_6) alternate assembly.
      Source sequence(s)
      BM991681, CN483948, L14848
      UniProtKB/Swiss-Prot
      Q29983
      Conserved Domains (2) summary
      cd07698
      Location:205296
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:24198
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    2. NM_001177519.2NP_001170990.1  MHC class I polypeptide-related sequence A isoform 2 (MICA*00801) precursor

      See identical proteins and their annotated locations for NP_001170990.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1*00801, also known as 1) is derived from the MICA*00801 allele. It contains a 4 nt insertion (rs9279200) that results in a frameshift and truncation of the CDS, compared to variant 1 (allele MICA*001). The resulting isoform (2) has a shorter and distinct C-terminus, compared to isoform 1. The MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence.
      Source sequence(s)
      AK299135, BM991681, BX342160, CN483948
      Consensus CDS
      CCDS56412.1
      UniProtKB/TrEMBL
      Q96QC4
      Related
      ENSP00000413079, OTTHUMP00000029088, ENST00000449934, OTTHUMT00000076101
      Conserved Domains (2) summary
      cd07698
      Location:205296
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:24198
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    3. NM_001289152.1NP_001276081.1  MHC class I polypeptide-related sequence A isoform 3 (MICA*00801)

      See identical proteins and their annotated locations for NP_001276081.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' exon and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream in-frame start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (3) is shorter at the N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 3; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence. Both variants 2 and 3 encode the same isoform.
      Source sequence(s)
      AK299135, AL645933, BM552351, BM991681
      Consensus CDS
      CCDS75421.1
      UniProtKB/TrEMBL
      A0A024RCL3
      UniProtKB/TrEMBL
      Q96QC4
      Related
      ENSP00000482382, ENST00000616296
      Conserved Domains (2) summary
      cd07698
      Location:108199
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:3101
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    4. NM_001289153.1NP_001276082.1  MHC class I polypeptide-related sequence A isoform 3 (MICA*00801)

      See identical proteins and their annotated locations for NP_001276082.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate 5' exon and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream in-frame start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (3) is shorter at the N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 2; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence. Both variants 2 and 3 encode the same isoform.
      Source sequence(s)
      AK299135, AL645933, BM991681, DT219772
      Consensus CDS
      CCDS75421.1
      UniProtKB/TrEMBL
      A0A024RCL3
      UniProtKB/TrEMBL
      Q96QC4
      Conserved Domains (2) summary
      cd07698
      Location:108199
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
      cl08246
      Location:3101
      MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
    5. NM_001289154.1NP_001276083.1  MHC class I polypeptide-related sequence A isoform 4 (MICA*00801)

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate 5' exon and uses an alternate splice site in an internal exon, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from an alternate start codon, compared to variant 1 (MICA*00801 allele). The encoded isoform (4) has a distinct and shorter N-terminus, compared to isoform 2. This RefSeq represents the MICA*00801 allelic form of variant 4; the MICA*00801 allele is found in the primary, ALT_REF_LOCI_2 and ALT_REF_LOCI_7 assembly units of the GRCh38 reference genome sequence.
      Source sequence(s)
      AK094237, AK299135, AL645933, BM991681, DT219772
      UniProtKB/TrEMBL
      A0A0G2JJ55
      UniProtKB/TrEMBL
      Q96QC4
      Conserved Domains (1) summary
      cd07698
      Location:67158
      IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p2 Primary Assembly

      Range
      31399784..31415315
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p2 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p2 ALT_REF_LOCI_2

      Range
      2880151..2895686
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p2 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p2 ALT_REF_LOCI_4

      Range
      2708377..2723902
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p2 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p2 ALT_REF_LOCI_6

      Range
      2659194..2671040
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p2 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p2 ALT_REF_LOCI_7

      Range
      2702061..2717592
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018917.2 Alternate CHM1_1.1

      Range
      31373316..31385170
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)