Identification and characterization of TRP14, a thioredoxin-related protein of 14 kDa. New insights into the specificity of thioredoxin function.
We have identified and characterized a 14-kDa human thioredoxin (Trx)-related protein designated TRP14. This cytosolic protein was expressed in all tissues and cell types examined, generally in smaller amounts than Trx1. Although TRP14 contains five cysteines, only the two Cys residues in its WCPDC motif were exposed and redox sensitive. Unlike Trx1, which was an equally good substrate for both Trx reductase 1 (TrxR1) and TrxR2, oxidized TRP14 was reduced by TrxR1 but not by TrxR2. Biochemical characterization of TRP14 suggested that, like Trx1, TRP14 is a disulfide reductase; its active site cysteine is sufficiently nucleophilic with the pK(a) value of 6.1; and its redox potential (-257 mV) is similar to those of other cellular thiol reductants. However, although TRP14 reduced small disulfide-containing peptides, it did not reduce the disulfides of known Trx1 substrates, ribonucleotide reductase, peroxiredoxin, and methionine sulfoxide reductase. These results suggest that TRP14 and Trx1 might act on distinct substrate proteins.
Jeong
Woojin
W
Laboratory of Cell Signaling, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yoon
Hae Won
HW
Lee
Seung-Rock
SR
Rhee
Sue Goo
SG
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D004220:Disulfides; D004926:Escherichia coli / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000502:physiology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010121:Oxytocin / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014667:Vasopressins / Q000737:chemistry
D004220:Disulfides; D007328:Insulin; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; C482341:TXNDC17 protein, human; D014667:Vasopressins; D010121:Oxytocin; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D003545:Cysteine; D010100:Oxygen