Background: MHC class I polypeptide-related sequence A(MICA) is a protein that in humans is encoded by the MICA gene. The MICA gene is located near HLA-B on chromosome 6. Nalabolu et al. (1996) showed that the MICA and MICB (602436) genes occur in a 200-kb region spanning the TNFA (191160) and TNFB (153440) cluster at chromosome 6p21.3. The 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. MICA is the ligand for NK cell activating receptor NKG2D.
NCBI and Uniprot Product Information
NCBI Description
MICA encodes the higly polymorphic MHC (HLA) class I chain-related gene A. The 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 intestinal epithelial gamma delta T cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]
Uniprot Description
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.
Research Articles on MICA
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Product Notes
The Human MICA mica (Catalog #AAA355266) is an ELISA Kit and is intended for research purposes only. The product is available for immediate purchase. The AAA355266 ELISA Kit recognizes Human MICA. AAA Biotech's MICA can be used in a range of immunoassay formats including, but not limited to, Quantitative sELISA (EIA). For quantitative detection of MICA in tissue lysates or cell culture supernates, human serum and plasma should be validated by end users. Researchers should empirically determine the suitability of the MICA mica for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "MICA, ELISA Kit" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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