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MGP001924

UniProt Annotations

Entry Information

Gene Name	MHC class I polypeptide-related sequence B
Protein Entry	MICB_HUMAN
UniProt ID	Q29980
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1 {ECO:0000269\|PubMed:12466900}; Synonyms=MICB1 {ECO:0000269\|PubMed:12466900}; IsoId=Q29980-1; Sequence=Displayed; Name=2 {ECO:0000269\|PubMed:12466900}; Synonyms=MICB2 {ECO:0000269\|PubMed:12466900}, ex3-del; IsoId=Q29980-2; Sequence=VSP_055246; Name=3 {ECO:0000269\|PubMed:17678727}; IsoId=Q29980-3; Sequence=VSP_052801, VSP_052802; Note=A GC to AG nucleotide substitution in intron 1 generates a splice junction which gives rise to an additional exon between exons 1 and 2. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000269\|PubMed:17678727};
Disease	Note=Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.
Disease	Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269\|PubMed:17003176}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The MICB*004 allele is associated with rheumatoid arthritis.
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. {ECO:0000269\|PubMed:11491531, ECO:0000269\|PubMed:11777960, ECO:0000269\|PubMed:9497295}.
Induction	By heat shock, oxidative stress, retinoic acid, IFN- alpha and the DNA methyltransferase inhibitor 5-aza-2'- deoxycytidine. Induction by IFN-alpha is impaired in patients with chronic hepatitis C virus infection. Down-regulated by human cytomegalovirus UL112 microRNA during viral infection which leads to decreased binding of KLRK1/NKG2D and reduced killing by natural killer cells. {ECO:0000269\|PubMed:11287116, ECO:0000269\|PubMed:12538683, ECO:0000269\|PubMed:12569559, ECO:0000269\|PubMed:17641203, ECO:0000269\|PubMed:18395517, ECO:0000269\|PubMed:9497295}.
Polymorphism	The following alleles of MICB are known: MICB001, MICB002, MICB003, MICB004, MICB005, MICB006, MICB007, MICB008, MICB009N, MICB010, MICB011, MICB012, MICB013, MICB014, MICB015, MICB016, MICB018, MICB019, MICB020, MICB021N and MICB022. MICB009N and MICB021N are null alleles which are not expressed. The sequence shown is that of MICB001. {ECO:0000305}.
Ptm	Proteolytically cleaved and released from the cell surface of tumor cells. {ECO:0000269\|PubMed:16698441}.
Similarity	Belongs to the MHC class I family. MIC subfamily. {ECO:0000255}.
Similarity	Contains 1 Ig-like C1-type (immunoglobulin-like) domain. {ECO:0000255}.
Subcellular Location	Cell membrane {ECO:0000250\|UniProtKB:Q29983}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:Q29983}. Note=Binding to human cytomegalovirus glycoprotein UL16 causes sequestration in the endoplasmic reticulum. {ECO:0000250\|UniProtKB:Q29983, ECO:0000269\|PubMed:12782710}.
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 MICB while HCST acts as an adapter molecule which enables signal transduction. Receptor-ligand interaction induces clustering of both proteins in ordered structures called immune synapses and also leads to their intercellular transfer. This is associated with a reduction in the cytotoxicity of KLRK1- expressing cells. Binds to human cytomegalovirus glycoprotein UL16 which causes sequestration of MICB in the endoplasmic reticulum and increases resistance to KLRK1-mediated cytotoxicity. {ECO:0000250\|UniProtKB:Q29983, ECO:0000269\|PubMed:11239445, ECO:0000269\|PubMed:11491531, ECO:0000269\|PubMed:12782710, ECO:0000269\|PubMed:16849432}.
Tissue Specificity	Widely expressed with the exception of the central nervous system where it is absent. Expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In hepatocellular carcinomas, expressed in tumor cells but not in surrounding non-cancerous tissue. {ECO:0000269\|PubMed:10359807, ECO:0000269\|PubMed:12569559, ECO:0000269\|PubMed:17565371}.