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marginal zone B- & B1-cell-specific protein; mesenteric estrogen-dependent adipose 7; MEDA-7; plasma cell-induced resident endoplasmic reticulum protein; plasma cell-induced resident ER protein; pERp1; proapoptotic caspase adapter protein (MZB1, MEDA7, PACAP, HSPC190)
Function:
- associates with IgM heavy chain & light chains & promotes IgM assembly & secretion
- may exert its effect by acting as a molecular chaperone or as an oxidoreductase (displays a low level of oxidoreductase activity)
- isoform 2 may be involved in regulation of apoptosis
- helps to diversify peripheral B-cell functions by regulating Ca+2 stores, antibody secretion & integrin activation
- acts as a hormone-regulated adipokine/proinflammatory cytokine implicated in causing chronic inflammation, affecting cellular expansion & blunting insulin response in adipocytes
- may have a role in the onset of insulin resistance
- forms an interchain disulfide bond with IgM monomers
- part of the ER chaperone complex, a multi-protein complex in the endoplasmic reticulum containing a large number of molecular chaperones which associates with unassembled incompletely folded immunoglobulin heavy chains (putative)
- isoform 2 interacts with CASP2 & CASP9
- interacts with HSP90B1 & PDIA3 (Ca+2-dependent)
Structure: belongs to the MZB1 family
Compartment:
- isoform 1: endoplasmic reticulum lumen, secreted
- isoform 2:
- cytoplasm
- diffuse granular localization in the cytoplasm surrounding the nucleus
Alternative splicing: named isoforms=5
Expression:
- widely expressed with highest levels in adult brain
- expression is frequently lower in intestinal-type gastric cancer
- down-regulated in primary B-cells early after ligand- stimulated activation
- up-regulated in bacterial lipopolysaccharides (LPS)- stimulated peritoneal macrophages
- in obese patients, more abundant in omental than in subcutaneous fat
General
nuclear protein
oxidoreductase
Properties
SIZE: entity length = 189 aa
MW = 21 kD
COMPARTMENT: cytoplasm
cell nucleus
endoplasmic reticulum
MOTIF: signal sequence {1-22}
cysteine residue {C50}
MODIFICATION: cysteine residue {C178}
cysteine residue {C53}
MODIFICATION: cysteine residue {C171}
active site
cysteine residue {C95}
MODIFICATION: cysteine residue {C143}
cysteine residue {C143}
MODIFICATION: cysteine residue {C95}
cysteine residue {C171}
MODIFICATION: cysteine residue {C53}
cysteine residue {C178}
MODIFICATION: cysteine residue {C50}
Prevents secretion from ER {186-189}
Database Correlations
OMIM 609447
UniProt Q8WU39
Pfam PF11938
Entrez Gene 51237
Kegg hsa:51237
References
- UniProt :accession Q8WU39
- Bonfoco E, Li E, Kolbinger F, Cooper NR.
Characterization of a novel proapoptotic caspase-2- and
caspase-9-binding protein.
J Biol Chem. 2001 Aug 3;276(31):29242-50. Epub 2001 May 11.
PMID: 11350957