MICA_HUMAN » MHC class I polypeptide-related sequence A

MICA_HUMAN » MHC class I polypeptide-related sequence A
Magnify MICA_HUMAN » MHC class I polypeptide-related sequence AEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
MICA_HUMAN » MHC class I polypeptide-related sequence A » MIC-A;
Hydrophobic Thickness 32.0 ± 2.3 Å
Tilt Angle 0 ± 2°
ΔGtransfer -22.9 kcal/mol
ΔGfold -20.9 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 307-328 (306-334)
Pathways

Natural killer cell mediated cytotoxicity (KEGG)

PDB 1b3j (24-297), 1hyr (C=24-297)
OPM none
Complexes

MICA:NKG2D_HUMAN

Interactions

1B08, Complex: 1B08.MICA:NKG2F, PubMed

HCST, Complex: MICA:HCST:NKG2D

NKG2D, Complex: MICA:NKG2D, PDBID: 1hyr, PubMed

Domains

AA: 24-200, PDBID: 1B3J, Subunit A, Seq Identity:100%, Class I Histocompatibility antigen, domains alpha 1 and 2

AA: 205-289, PDBID: 1B3J, Subunit A, Seq Identity:100%, Immunoglobulin C1-set domain

UniProt annotation for MICA_HUMAN » MHC class I polypeptide-related sequence A
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.

SUBUNIT: 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.

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.

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.

DISEASE: Note=Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma.

DISEASE: Psoriasis 1 (PSORS1) OMIM: 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.

DISEASE: Psoriatic arthritis (PSORAS) OMIM: 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). 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.

UniProt features for MICA_HUMAN » MHC class I polypeptide-related sequence A
SIGNAL 1 23
CHAIN 24 383 MHC class I polypeptide-related sequence A.
DOMAIN 207 296 Ig-like C1-type.
DISULFID 59 64
DISULFID 119 187
DISULFID 225 282
Amino Acid Sequence for MICA_HUMAN » MHC class I polypeptide-related sequence A
MGLGPVFLLL AGIFPFAPPG AAAEPHSLRY NLTVLSWDGS VQSGFLTEVH LDGQPFLRCD RQKCRAKPQG QWAEDVLGNK TWDRETRDLT GNGKDLRMTL AHIKDQKEGL HSLQEIRVCE IHEDNSTRSS QHFYYDGELF LSQNLETKEW TMPQSSRAQT LAMNVRNFLK EDAMKTKTHY HAMHADCLQE LRRYLKSGVV LRRTVPPMVN VTRSEASEGN ITVTCRASGF YPWNITLSWR QDGVSLSHDT QQWGDVLPDG NGTYQTWVAT RICQGEEQRF TCYMEHSGNH STHPVPSGKV LVLQSHWQTF HVSAVAAAAI FVIIIFYVRC CKKKTSAAEG PELVSLQVLD QHPVGTSDHR DATQLGFQPL MSDLGSTGST EGA