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

Gene ID: 100507436, updated on 30-Nov-2020

Summary

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 IMGT/GENE-DB:MICA; MIM:600169
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]
Expression
Ubiquitous expression in lung (RPKM 8.7), endometrium (RPKM 7.4) and 25 other tissues See more
Orthologs

Genomic context

See MICA in Genome Data Viewer
Location:
6p21.33
Exon count:
7
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (31400711..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 MICA antisense RNA 1 Neighboring gene long intergenic non-protein coding RNA 1149 Neighboring gene major histocompatibility complex, class I, X (pseudogene)

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

Associated conditions

Description Tests
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.
GeneReviews: Not available
A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.
GeneReviews: Not available
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
GeneReviews: Not available
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
GeneReviews: Not available
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
GeneReviews: Not available
Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
GeneReviews: Not available
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma.
GeneReviews: Not available
Genome-wide association study of susceptibility loci for cervical cancer.
GeneReviews: Not available
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
GeneReviews: Not available
Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome-wide association study.
GeneReviews: Not available
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.
GeneReviews: Not available
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
GeneReviews: Not available
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 (SF2) Nef moderately downregulates MICA A3.01 T cells and HeLa TZM-bl cells PubMed
nef HIV-1 Nef downregulates cell surface expression of MICA, ULBP1 and ULBP2 in natural killer (NK) cells PubMed
Vpu vpu HIV-1 (NL4-3) Vpu moderately downregulates MICA as shown in A3.01 T cells and HeLa TZM-bl 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

  • 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 
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 IBA
Inferred from Biological aspect of Ancestor
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 
regulation of immune response TAS
Traceable Author Statement
more info
 
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
 
external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
MHC class I polypeptide-related sequence A
Names
HLA class I antigen
MHC class I chain-related protein A
MHC class I related chain A
MHC class I related sequence A
major histocompatibility complex class I chain-related protein A
stress inducible class I homolog
truncated MHC class I polypeptide-related sequence A
truncated MICA

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_034139.1 RefSeqGene

    Range
    8812..20630
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000247.3NP_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, 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_001177519.3NP_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
    ENSP00000413079.1, ENST00000449934.7
    Conserved Domains (2) summary
    cd07698
    Location:205296
    IgC_MHC_I_alpha3; Class I major histocompatibility complex (MHC) alpha chain immunoglobulin domain
    cl08246
    Location:25198
    MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
  3. NM_001289152.2NP_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, Q96QC4
    Related
    ENSP00000482382.1, ENST00000616296.4
    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_001289153.2NP_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, BM991681, DT219772
    Consensus CDS
    CCDS75421.1
    UniProtKB/TrEMBL
    A0A024RCL3, 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_001289154.2NP_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, BM991681, DT219772
    UniProtKB/TrEMBL
    A0A0G2JJ55, Q96QC4
    Related
    ENSP00000501157.1, ENST00000674069.1
    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 Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    31400711..31415315
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p13 ALT_REF_LOCI_2

    Range
    2881078..2895686
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p13 ALT_REF_LOCI_4

    Range
    2709304..2723902
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p13 ALT_REF_LOCI_6

    Range
    2659222..2671040
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p13 ALT_REF_LOCI_7

    Range
    2702988..2717592
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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