MHC class I polypeptide-related sequence A

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MICA
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesMICA, MIC-A, PERB11.1, MHC class I polypeptide-related sequence A
External IDsGeneCards: MICA
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for MICA
Genomic location for MICA
Band6p21.33Start31,399,784 bp[1]
End31,415,315 bp[1]
RNA expression pattern
PBB GE MICA 205904 at fs.png

PBB GE MICA 205905 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001289154
NM_000247
NM_001177519
NM_001289152
NM_001289153

n/a

RefSeq (protein)

NP_000238
NP_001170990
NP_001276081
NP_001276082
NP_001276083

n/a

Location (UCSC)Chr 6: 31.4 – 31.42 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

MHC class I polypeptide-related sequence A (MICA) is a highly polymorphic cell surface glycoprotein encoded by the MICA gene located within MHC locus.[3] MICA is related to MHC class I and it has similar domain structure, however, it is not associated with β2-microglobulin nor binds peptides as conventional MHC class I molecules do.[4] MICA rather functions as a stress-induced ligand (as a danger signal) for integral membrane protein receptor NKG2D ("natural-killer group 2, member D"). MICA is broadly recognized by NK cells, γδ T cells, and CD8+ αβ T cells which carry NKG2D receptor on their cell surface and which are activated via this interaction.[5]

Structure[edit]

The MICA gene is highly polymorphic in humans with more than 50 defined alleles. It is located on chromosome 6 and the protein is expressed in two isoforms formed by alternative splicing: MICA1 and MICA2 which is lacking exon 3.[6] MICA contains external α1α2α3 domain, transmembrane segment and C-terminal cytoplasmic tail. It binds in a form of monomer to a KLRK1/NKG2D homodimer.[7]

There are no orthologs of the MICA in mice species.[8]

Expression[edit]

Expression of MICA can be upregulated by heat shock[4] or by exposure of the cells to DNA damaging conditions (for example ionizing radiation, chromatin-modifying interventions and inhibitors of DNA replication). The expression can be as well affected by some infectious agents such as human cytomegalovirus (HCMV), human adenovirus 5, M. tuberculosis or diarrheagenic E.coli.[7]

In the negative regulation of MICA expression, microRNA-183 plays an important. It downregulates its expression after exposure to transforming growth factor beta (TGFβ).[9]

In normal tissue, MICA is expressed mainly intracellularly with just a small fraction appearing on the surface of some epithelial cells.[10] There is no expression of MICA in the cells of the central nervous system (CNS). [7]

Function[edit]

MICA plays the role of stress-induced self-antigen and serves as a ligand for the KLRK1/NKG2D receptor. Engagement of NKG2D-MICA results in activation of effector cytolytic responses of T cells and NK cells against epithelial tumour cells (or other stressed cells) expressing MICA on their surface.[5]

As a defence mechanism, tumour cells are able to avoid the recognition of MICA by immune system through proteolytic shedding of the surface expressed protein by the cooperation of disulfide isomerase (ERp5) and ADAM (a disintegrin and metalloproteinase) and MMP (matrix metalloproteinase) proteases targeting membrane-proximal α3 domain.[11] High levels of MICA in the serum of tumour patients are possitively related to tumour size and poor prognosis.[12]

Variations in the MICA gene are also associated with susceptibility to psoriasis 1 and psoriatic arthritis and MICA-specific antibodies or its shedding are involved in the monoclonal gammopathy of undetermined significance´s (MGUS) progression to multiple myeloma.[7]

See also[edit]

References[edit]

  1. ^ a b c ENSG00000235233, ENSG00000204520, ENSG00000183214, ENSG00000233051 GRCh38: Ensembl release 89: ENSG00000231225, ENSG00000235233, ENSG00000204520, ENSG00000183214, ENSG00000233051 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:".
  3. ^ Bahram S, Bresnahan M, Geraghty DE, Spies T (July 1994). "A second lineage of mammalian major histocompatibility complex class I genes". Proceedings of the National Academy of Sciences of the United States of America. 91 (14): 6259–63. doi:10.1073/pnas.91.14.6259. PMC 44180. PMID 8022771.
  4. ^ a b Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T (October 1996). "Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium". Proceedings of the National Academy of Sciences of the United States of America. 93 (22): 12445–50. doi:10.1073/pnas.93.22.12445. PMC 38011. PMID 8901601.
  5. ^ a b Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (July 1999). "Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA". Science. 285 (5428): 727–9. doi:10.1126/science.285.5428.727. PMID 10426993.
  6. ^ Zou Y, Stastny P (December 2002). "Alternatively spliced forms of MICA and MICB lacking exon 3 in a human cell line and evidence of presence of similar RNA in human peripheral blood mononuclear cells". Immunogenetics. 54 (9): 671–4. doi:10.1016/s0198-8859(02)00518-9. PMID 12466900.
  7. ^ a b c d Universal protein resource accession number Q29983 for "MICA - MHC class I polypeptide-related sequence A precursor - Homo sapiens (Human) - MICA gene & protein" at UniProt.
  8. ^ Mistry AR, O'Callaghan CA (August 2007). "Regulation of ligands for the activating receptor NKG2D". Immunology. 121 (4): 439–47. doi:10.1111/j.1365-2567.2007.02652.x. PMC 2265965. PMID 17614877.
  9. ^ Trinh, Thu Le; Kandell, Wendy M.; Donatelli, Sarah S.; Tu, Nhan; Tejera, Melba M.; Gilvary, Danielle L.; Eksioglu, Erika A.; Burnette, Alexis; Adams, William A. (2019-01-17). "Immune evasion by TGFβ-induced miR-183 repression of MICA/B expression in human lung tumor cells". OncoImmunology: 1–11. doi:10.1080/2162402x.2018.1557372. ISSN 2162-402X.
  10. ^ Ghadially H, Brown L, Lloyd C, Lewis L, Lewis A, Dillon J, Sainson R, Jovanovic J, Tigue NJ, Bannister D, Bamber L, Valge-Archer V, Wilkinson RW (April 2017). "MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue". British Journal of Cancer. 116 (9): 1208–1217. doi:10.1038/bjc.2017.79. PMC 5418453. PMID 28334733.
  11. ^ Ferrari de Andrade L, Tay RE, Pan D, Luoma AM, Ito Y, Badrinath S, Tsoucas D, Franz B, May KF, Harvey CJ, Kobold S, Pyrdol JW, Yoon C, Yuan GC, Hodi FS, Dranoff G, Wucherpfennig KW (March 2018). "Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity". Science. 359 (6383): 1537–1542. doi:10.1126/science.aao0505. PMID 29599246.
  12. ^ Li JJ, Pan K, Gu MF, Chen MS, Zhao JJ, Wang H, Liang XT, Sun JC, Xia JC (March 2013). "Prognostic value of soluble MICA levels in the serum of patients with advanced hepatocellular carcinoma". Chinese Journal of Cancer. 32 (3): 141–8. doi:10.5732/cjc.012.10025. PMC 3845598. PMID 22704489.

Further reading[edit]