Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A microsomal protein having N-terminal amino acid sequence SDVLELTDEN, was initially described as a phosphatidyl inositol-specific phospholipase C alpha when its cDNA was cloned (Bennett et al., Nature, 334, 268, 1988). Later, this protein, with an estimated molecular mass of 54 to 60 kDa, was shown to lack the phospholipase activity and instead a protein disulfide oxidoreductase and a thiol protease activities were ascribed to it. Following evidences indicated that the protein in question is the carnitine medium/long chain acyltransferase (CPT) of microsomes that was recently purified as a approximately 54 kDa protein (Murthy and Bieber, Protein Exp. Purif. 3, 75, 1992). First, the N-terminal amino acids of the microsomal CPT showed 100% homology to the sequence described above. Second, during purification of this CPT, the oxidoreductase and the thiol protease activities of the microsomes became separated from the CPT and these other activities were not found in the approximately 900 fold enriched CPT preparations. Third, an antibody to this protein did not immunoprecipitate oxidoreductase of the solubilized microsomal extract but precipitated the CPT. This same protein has been studied by others as the ERp61 (endoplasmic reticulum protein), GRP58 (glucose regulated protein), and HIP-70 (hormone induced protein) but its function was not identified.
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PMID:Carnitine medium/long chain acyltransferase of microsomes seems to be the previously cloned approximately 54 kDa protein of unknown function. 823 44

The proper folding and assembly of major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER) is an intricate process involving a number of components. Nascent heavy chains of MHC class I molecules, translocated into the ER membrane, are rapidly glycosylated and bind the transmembrane chaperone calnexin. In humans, after dissociation from calnexin, fully oxidized MHC class I heavy chains associate with beta 2-microglobulin (beta 2m) and the soluble chaperone calreticulin. This complex interacts with another transmembrane protein, tapasin, which is believed to assist in MHC class I folding as well as in mediating the interaction between assembling MHC class I molecules and the transporter associated with antigen processing (TAP). The TAP heterodimer (TAP1-TAP2) introduces the final component of the MHC class I molecule by translocating peptides, predominately generated by the proteasome, from the cytosol into the ER where they can bind dimers of beta 2M and the MHC class I heavy chain. Recently, the thiol oxidoreductase ERp57--also known as GRP58, ERp61, ER60, Q2, HIP-70, and CPT and first misidentified as phospholipase C-alpha--has been shown to bind in conjunction with calnexin or calreticulin to a number of newly synthesized ER glycoproteins when their N-linked glycans are trimmed by glucosidases I and II. It was speculated that ERp57 is a generic component of the glycan-dependent ER quality control system. Here, we show that ERp57 is a component of the MHC class I peptide-loading complex. ERp57 might influence the folding of MHC class I molecules at a critical step in peptide loading.
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PMID:The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex. 963 23

Mitomycin C (MMC) is an anticancer drug that requires reductive activation to exert its toxicity. MMC is known to cross-link DNA that contributes significantly to the cytotoxicity and consequent cell death. Cytosolic NADPH:quinone oxidoreductase 1 (NQO1) and microsomal enzymes have been shown to mediate MMC-induced DNA cross-linking. However, NQO1 plays only a minor role, indicating presence of other cytosolic enzymes/proteins that contribute to this process. In this study, we have characterized a unique cytosolic activity in NQO1-null mice that catalyzed MMC-induced DNA cross-linking. This activity was cofactor independent and dicoumarol insensitive. The unique cytosolic activity was purified to homogeneity. The peptide sequencing of the purified protein identified the unique cytosolic activity as GRP58 (M(r) 58,000 glucose-regulatory protein), also known as GRp57/ER60/ERp61/HIP-70/Q2 and CPT. Immunodepletion of NQO1-null mice liver cytosol and partially purified fractions with anti-GRP58 antibody led to a complete loss of GRP58 protein and consequent significant reduction of MMC-induced DNA cross-linking. Mouse cDNA encoding GRP58 was isolated and sequenced. Chinese hamster ovary cells permanently overexpressing GRP58 showed increased MMC-induced DNA cross-linking and increased cytotoxicity on exposure to MMC. Bacterially expressed and purified GRP58 increased the MMC-induced DNA cross-linking when added to mouse cytosolic samples. A tissue array analysis indicated that GRP58 is ubiquitously expressed among mouse tissues, although at different levels. Expression analysis using matched human tumor/normal array revealed an up-regulation of GRP58 in breast, uterus, lung, and stomach tumors compared with normal tissues of similar origin.
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PMID:Role of GRP58 in mitomycin C-induced DNA cross-linking. 1452 30