MICA Antibody – Mouse Monoclonal

This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

Function: Seems to have no role in antigen presentation. 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. Ref.28 Ref.32 Ref.39

Subunit structure: Unlike classical MHC class I 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 which is required for release of MICA from tumor cells. Interacts with human cytomegalovirus/HHV-5 protein UL142. Ref.26 Ref.27 Ref.32 Ref.33 Ref.35 Ref.36 Ref.39 Ref.48

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. Ref.26 Ref.30 Ref.39 Ref.50

Tissue specificity: Widely expressed with the exception of the central nervous system where it is absent. 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. Ref.26 Ref.27 Ref.30 Ref.31 Ref.34 Ref.39 Ref.45 Ref.49

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. Ref.26 Ref.27 Ref.28 Ref.30 Ref.32 Ref.33 Ref.38 Ref.39 Ref.40 Ref.44 Ref.46 Ref.47 Ref.50

Post-translational modification: N-glycosylated. Glycosylation is not essential for interaction with KLRK1/NKG2D but enhances complex formation. Ref.26 Ref.39Proteolytically cleaved and released from the cell surface of tumor cells which impairs KLRK1/NKG2D expression and T-cell activation. Ref.42 Ref.43

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.

Involvement in disease: Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma.Psoriasis 1 (PSORS1) [MIM:177900]: 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.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.Psoriatic arthritis (PSORAS) [MIM:607507]: 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 rheumatoid like 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).Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Miscellaneous: Recognized by antibodies in the sera of some organ transplant recipients and may be a target molecule in allograft rejection. Ref.35

Sequence similarities: Belongs to the MHC class I family. MIC subfamily.Contains 1 Ig-like C1-type (immunoglobulin-like) domain.