MHC class I polypeptide-related sequence A (MIC-A, MICA, PERB111)

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Function

seems to have no role in antigen presentation
acts as a stress-induced self-antigen recognized by gamma delta T-cells
ligand for the KLRK1/NKG2D receptor
binding to KLRK1 leads to cell lysis
unlike classical MHC class 1 molecules, does not form a heterodimer with beta-2-microglobulin
binds as a monomer to a KLRK1/NKG2D homodimer
KLRK1 forms a complex with HCST/DAP10 in which KLRK1 binds MICA while HCST acts as an adapter molecule which enables signal transduction
interacts with PDIA6 on the surface of tumor cells, leading to disulfide bond reduction required for release of MICA from tumor cells

cell membrane, cytoplasm
expressed on the cell surface in gastric epithelium, endothelial cells & fibroblasts
expressed in cytoplasm in keratinocytes & monocytes
infection with human adenovirus 5 suppresses cell surface expression due to the adenoviral E3-19K protein which causes retention in the endoplasmic reticulum

widely expressed, except in the central nervous system
not expressed in the central nervous system
expressed predominantly in gastric epithelium & in monocytes, keratinocytes, endothelial cells, fibroblasts & in the outer layer of Hassal's corpuscles within the medulla of normal thymus
in skin, expressed mainly in the keratin layers, basal cells, ducts & follicles
also expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate & colon
in thyomas, overexpressed in cortical & medullar epithelial cells
tumors expressing MICA display increased levels of gamma delta T cells
induced by heat shock, infection with human cytomegalovirus (HCMV), human adenovirus 5, M tuberculosis & diarrheagenic E.coli, & by exposure to DNA damaging conditions such as high doses of ionizing radiation, chromatin-modifying treatments & inhibitors of DNA replication
the HCMV UL142 protein causes down-regulation of the full-length protein but not of the truncated MICA*008 allele

role in progression of MGUS (monoclonal gammopathy of undetermined significance)
genetic variation in MICA is associated with:
- susceptibility to psoriasis 1 (PSORS1)
- susceptibility to psoriatic arthritis
recognized by autoantibodies in some organ transplant recipients & may play role in allograft rejection

many alleles of MICA are known: MICA*001, MICA*002, MICA*004, MICA*005, MICA*006, MICA*007, MICA*008, MICA*009, MICA*010, MICA*011, MICA*012, MICA*013, MICA*014, MICA*015, MICA*016, MICA*017, MICA*018, MICA*019, MICA*020, MICA*022, MICA*023, MICA*024, MICA*025, MICA*026, MICA*027, MICA*028, MICA*029, MICA*030, MICA*031, MICA*032, MICA*033, MICA*034, MICA*035, MICA*036, MICA*037, MICA*038, MICA*039, MICA*040, MICA*041, MICA*042, MICA*043, MICA*044, MICA*045, MICA*046, MICA*047, MICA*048, MICA*049, MICA*050, MICA*051, MICA*052, MICA*053, MICA*054 & MICA*055