MHC class I polypeptide-related sequence A (MICA)

MHC class I chain-related molecules A (MICA) is one of the genes in the HLA class I region, which belongs to MHC class I family. It is the member of the non-classical class I family that displays the greatest degree of polymorphism. The MICA protein product is expressed on the cell surface, although unlike canonical class I molecules does not seem to associate with beta-2-microglobulin. It is thought that MICA functions as a stress-induced antigen that is broadly recognized by NK cells, NKT cells, and most of the subtypes of T cells. The Natural killer group 2D (NKG2D), a C-type lectin-like activating immunoreceptor, is a receptor of MICA, which was detected on most gammadelta T cells, CD8+ alphabeta T cells, and natural killer (NK) cells. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gammadelta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. The MICA system is a novel, avidin-free immunohistochemical detection system that provides a significant increase in sensitivity compared to traditional immunodetection systems.

MHC class I polypeptide-related sequence A (MICA) Related Areas

Immunology>>Adaptive Immunity>>Major Histocompatibility Complex>>MICA

MHC class I polypeptide-related sequence A (MICA) Alternative Names

MICA, DAMA-345G11.2, FLJ36918, FLJ60820, MGC111087, MGC21250, MIC-A, PERB11.1 [Homo sapiens]

Summaries for MHC class I polypeptide-related sequence A (MICA)

Entrez Gene summary for MICA:

MICA encodes the higly polymorphic MHC (HLA) class I chain-related gene A. MICA is expressed on the cell surface, although unlike canonical class I molecules does not seem to associate with beta-2-microglobulin. It is thought that MICA functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

Wikipedia summary for MHC class I polypeptide-related sequence A (MICA):

MHC class I polypeptide-related sequence A is a protein that in humans is encoded by the MICA gene. MICA is the ligand for NK cell activating receptor NKG2D

Human MHC class I polypeptide-related sequence A (MICA) Protein General Information

 

• Protein names: MHC class I polypeptide-related sequence A, Short name=MIC-A
• Sequence length: 383 AA.
• Sequence similarities: N-glycosylated. Glycosylation is not essential for interaction with KLRK1/NKG2D but enhances complex formation.
• Post-translational modification: MICA belongs to the MHC class I family. MIC subfamily. MICA contains 1 Ig-like C1-type (immunoglobulin-like) domain.
• Polymorphism: The following 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 and MICA*056. The sequence shown is that of MICA*001.
• Miscellaneous: Recognized by antibodies in the sera of some organ transplant recipients and may be a target molecule in allograft rejection.
• Subunit structure: Unlike classical MHC class I molecules, does not form a heterodimer with beta-2-microglobulin. MICA 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. MICA interacts with PDIA6 on the surface of tumor cells, leading to disulfide bond reduction which is required for release of MICA from tumor cells.
• Subcellular location: Cell membrane; Single-pass type I membrane protein. Cytoplasm. Note: Expressed on the cell surface in gastric epithelium, endothelial cells and fibroblasts and in the cytoplasm in keratinocytes and monocytes. Infection with human adenovirus 5 suppresses cell surface expression due to the adenoviral E3-19K protein which causes retention in the endoplasmic reticulum.
• Tissue specificity: MICA is widely expressed with the exception of the central nervous system where it is absent. MICA is expressed predominantly in gastric epithelium and also in monocytes, keratinocytes, endothelial cells, fibroblasts and 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 and follicles. Also expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In thyomas, overexpressed in cortical and medullar epithelial cells. Tumors expressing MICA display increased levels of gamma delta T-cells.
• Induction: By heat shock, by infection with human cytomegalovirus (HCMV), human adenovirus 5, M.tuberculosis and diarrheagenic E.coli, and by exposure to DNA damaging conditions such as high doses of ionizing radiation, chromatin-modifying treatments and inhibitors of DNA replication. The HCMV UL142 protein causes down-regulation of the full-length protein but not of the truncated MICA*008 allele.
• Involvement in disease: Note=Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma. Genetic variations in MICA may be a cause of susceptibility to psoriasis type 1 (PSORS1) [MIM:177900]. Psoriasis is a common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Genetic variation in MICA is a cause of susceptibility to psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).

General information above from UniProt

Function for MHC class I polypeptide-related sequence A (MICA) Protein

UniProtKB:

MHC class I polypeptide-related sequence A (MICA) seems to have no role in antigen presentation. MICA acts as a stress-induced self-antigen that is recognized by gamma delta T-cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.

Genatlas:

• MICA functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells
• MICA, and MICB, ligands of the KLRK1, which activates NK cells and costimulates effector T cells, are inducibly expressed under harmful conditions, such as malignancies and microbial infections (Pubmed 17202358)
• non-peptide-presenting, tightly regulated, stress-induced MHC-like molecule (Pubmed 20460636)

Homology for human MHC class I polypeptide-related sequence A (MICA)

• homolog to micb