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MICA
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1B3J, 1HYR
Identifiers
Aliases	MICA, MIC-A, PERB11.1, MHC class I polypeptide-related sequence A, MHC class I chain–related protein A, MHC class I polypeptide–related protein A
External IDs	OMIM: 600169; MGI: 2179989; GeneCards: MICA; OMA:MICA - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	31,415,315 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	18,599,327 bp
RNA expression pattern
	Top expressed in
	Descending thoracic aorta; ; left ovary; ; popliteal artery; ; tibial arteries; ; body of uterus; ; ascending aorta; ; right uterine tube; ; stromal cell of endometrium; ; left coronary artery; ; right ovary;
	Top expressed in
	urinary bladder; ; uterus; ; lung; ; ovary; ; white adipose tissue; ; adrenal gland; ; zone of skin; ; esophagus; ; muscle tissue; ; skeletal muscle tissue;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	beta-2-microglobulin binding; protein binding; natural killer cell lectin-like receptor binding;
Cellular component	cytoplasm; integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; cell surface; extracellular space; external side of plasma membrane;
Biological process	cytolysis; adaptive immune response; negative regulation of natural killer cell activation; immune system process; gamma-delta T cell activation; response to heat; immune response to tumor cell; cellular response to DNA damage stimulus; defense response to bacterium; defense response to virus; regulation of immune response; negative regulation of natural killer cell mediated cytotoxicity; viral process; T cell mediated cytotoxicity; natural killer cell mediated cytotoxicity; immune response; natural killer cell activation; susceptibility to natural killer cell mediated cytotoxicity;
	Sources:Amigo / QuickGO
Orthologs
	100507436
	243864
ENSG00000231225; ENSG00000235233; ENSG00000204520; ENSG00000183214; ENSG00000233051;
	n/a
	ENSMUSG00000040987
	Q29983
	Q8HWE5
	NM_001289154; NM_000247; NM_001177519; NM_001289152; NM_001289153
	NM_153760; NM_153761
	NP_000238; NP_001170990; NP_001276081; NP_001276082; NP_001276083
	NP_715641; NP_715642
	Wikidata
View/Edit Human	View/Edit Mouse

MHC class I polypeptide–related sequence A (MICA) is a highly polymorphic cell surface glycoprotein encoded by the MICA gene located within MHC locus.^[5] 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.^[6] 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.^[7]

Structure

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.^[8] MICA contains external α1α2α3 domain, transmembrane segment and C-terminal cytoplasmic tail. It binds in a form of monomer to a KLRK1/NKG2D homodimer.^[9]

There are no orthologs of the MICA in mice species.^[10]

Expression

Expression of MICA can be upregulated by heat shock^[6] 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, diarrheagenic E.coli,^[9] or human papillomavirus (HPV).^[11]

microRNA-183 downregulates MICA expression after exposure to transforming growth factor beta (TGFβ).^[12]

In normal tissue, MICA is expressed mainly intracellularly with just a small fraction appearing on the surface of some epithelial cells.^[13] There is no expression of MICA in the cells of the central nervous system (CNS).^[9]

Function

MICA plays the role of stress-induced self-antigen and serves as a ligand for the KLRK1/NKG2D killer activation receptor.^[14] Engagement of NKG2D-MICA results in activation of effector cytolytic responses of T cells and NK cells against epithelial tumor cells (or other stressed cells) expressing MICA on their surface.^[7]

As a defense mechanism, tumor cells are able to avoid recognition of MICA by the 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.^[15] High levels of MICA in the serum of tumor patients are positively related to tumor size and poor prognosis.^[16]

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.^[9]