MICB_HUMAN » MHC class I polypeptide-related sequence B

MICB_HUMAN » MHC class I polypeptide-related sequence B
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
MICB_HUMAN » MHC class I polypeptide-related sequence B » MIC-B;
Hydrophobic Thickness 33.0 ± 2.1 Å
Tilt Angle 0 ± 9°
ΔGtransfer -18.1 kcal/mol
ΔGfold -9.3 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 312-334 (311-338)
Pathways

Immune System (Reactome)

Natural killer cell mediated cytotoxicity (KEGG)

PDB 2wy3 (A/C=24-341), 1je6 (A=24-297)
OPM none
Complexes none
Interactions

HCST, Complex: MICB:HCST:NKG2D, PubMed

NKG2D, Complex: NKG2D:MICB, PubMed

NKG2F, Complex: NKG2F:MICB, PubMed

Domains

AA: 24-201, PDBID: 1JE6, Subunit A, Seq Identity:100%, Class I Histocompatibility antigen, domains alpha 1 and 2

AA: 205-289, PDBID: 1JE6, Subunit A, Seq Identity:100%, Immunoglobulin C1-set domain

UniProt annotation for MICB_HUMAN » MHC class I polypeptide-related sequence B
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 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.

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.

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.

DISEASE: Rheumatoid arthritis (RA) OMIM: 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. susceptibility is associated with variations affecting the gene represented in this entry. The MICB*004 allele is associated with rheumatoid arthritis.

DISEASE: Note=Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.

UniProt features for MICB_HUMAN » MHC class I polypeptide-related sequence B
SIGNAL 1 22 Potential.
CHAIN 23 383 MHC class I polypeptide-related sequence B.
DOMAIN 207 298 Ig-like C1-type.
DISULFID 119 187
DISULFID 225 282
Amino Acid Sequence for MICB_HUMAN » MHC class I polypeptide-related sequence B
MGLGRVLLFL AVAFPFAPPA AAAEPHSLRY NLMVLSQDES VQSGFLAEGH LDGQPFLRYD RQKRRAKPQG QWAEDVLGAK TWDTETEDLT ENGQDLRRTL THIKDQKGGL HSLQEIRVCE IHEDSSTRGS RHFYYDGELF LSQNLETQES TVPQSSRAQT LAMNVTNFWK EDAMKTKTHY RAMQADCLQK LQRYLKSGVA IRRTVPPMVN VTCSEVSEGN ITVTCRASSF YPRNITLTWR QDGVSLSHNT QQWGDVLPDG NGTYQTWVAT RIRQGEEQRF TCYMEHSGNH GTHPVPSGKV LVLQSQRTDF PYVSAAMPCF VIIIILCVPC CKKKTSAAEG PELVSLQVLD QHPVGTGDHR DAAQLGFQPL MSATGSTGST EGA