MHC class I polypeptide-related sequence B (MIC-B, MICB, PERB112)

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 - 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 & also leads to their intercellular transfer; this is associated with a reduction in the cytotoxicity of KLRK1-expressing cells Structure: - belongs to the MHC class I family, MIC subfamily - contains 1 Ig-like C1-type (immunoglobulin-like) Compartment: - cell membrane - binding to human cytomegalovirus glycoprotein UL16 causes sequestration in the endoplasmic reticulum Alternative splicing: named isoforms=3 Note: - GC to AG nucleotide substitution in intron 1 generates a splice junction which gives rise to an additional exon between exons 1 & 2 - may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay Expression: - widely expressed with the exception of the central nervous system where it is absent - induced by heat shock, oxidative stress, retinoic acid, IFN-alpha & the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Polymorphism: - the following alleles of MICB are known: MICB*001, MICB*002, MICB*003, MICB*004, MICB*005, MICB*006, MICB*007, MICB*008, MICB*009N, MICB*010, MICB*011, MICB*012, MICB*013, MICB*014, MICB*015, MICB*016, MICB*018, MICB*019, MICB*020, MICB*021N & MICB*022 - MICB*009N & MICB*021N are null alleles which are not expressed - the sequence shown is that of MICB*001 Pathology: - expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate & colon - in hepatocellular carcinomas, expressed in tumor cells but not in surrounding non-cancerous tissue - proteolytically cleaved & released from the cell surface of tumor cells - the MICA*004 allele is associated with susceptibility to rheumatoid arthritis - binds to human cytomegalovirus glycoprotein UL16 which causes sequestration of MICB in the endoplasmic reticulum & increases resistance to KLRK1-mediated cytotoxicity - genetic variation in MICB is associated with cytomegalovirus & herpes simplex virus I seropositivity & this may be associated with schizophrenia risk - 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 & reduced killing by natural killer cells

General

glycoprotein membrane protein

Properties

SIZE: entity length = 383 aa MW = 43 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-22} cysteine residue {C119} MODIFICATION: cysteine residue {C187} N-glycosylation site {N164} cysteine residue {C187} MODIFICATION: cysteine residue {C119} immunoglobulin superfamily domain {207-298} MOTIF: N-glycosylation site {N210} N-glycosylation site {N220} cysteine residue {C225} MODIFICATION: cysteine residue {C282} N-glycosylation site {N261} cysteine residue {C282} MODIFICATION: cysteine residue {C225} transmembrane domain {310-330}

Database Correlations

OMIM correlations UniProt Q29980 PFAM correlations Kegg hsa:4277

References

UniProt :accession Q29980