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

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 Structure: - N-glycosylated (glycosylation is not essential for interaction with KLRK1/NKG2) - belongs to the MHC class I family, MIC subfamily - contains 1 Ig-like C1-type (immunoglobulin-like) domain Compartment: - 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 Alternative splicing: named isoforms=2 Expression: - 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 Pathology: - role in progression of MGUS (monoclonal gammopathy of undetermined significance) - genetic variation in MICA is associated with: a) susceptibility to psoriasis 1 (PSORS1) b) susceptibility to psoriatic arthritis - recognized by autoantibodies in some organ transplant recipients & may play role in allograft rejection Polymorphism: - 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

General

glycoprotein membrane protein

Properties

SIZE: entity length = 383 aa MW = 43 kD COMPARTMENT: cytoplasm plasma membrane endoplasmic reticulum MOTIF: signal sequence {1-23} N-glycosylation site {N31} cysteine residue {C59} MODIFICATION: cysteine residue {C64} cysteine residue {C64} MODIFICATION: cysteine residue {C59} N-glycosylation site {N79} cysteine residue {C119} MODIFICATION: cysteine residue {C187} cysteine residue {C187} MODIFICATION: cysteine residue {C119} immunoglobulin superfamily domain {207-296} MOTIF: N-glycosylation site {N210} N-glycosylation site {N220} cysteine residue {C225} MODIFICATION: cysteine residue {C282} N-glycosylation site {N261} cysteine residue {C282} MODIFICATION: cysteine residue {C225} transmembrane domain {308-328}

Database Correlations

OMIM correlations UniProt Q29983 PFAM correlations Kegg hsa:4276

References

UniProt :accession Q29983