Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin (TRX)-like superfamily is a large, diverse group of proteins containing a TRX fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include the families of TRX, protein disulfide isomerase (PDI), tlpA, glutaredoxin, NrdH redoxin, and bacterial Dsb proteins (DsbA, DsbC, DsbG, DsbE, DsbDgamma). Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins, glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274108175  56 EKVPIEWLLDSanILVLYFSMRDSDRSDNIMSQFYEFYENARFKNLPIEVINIPMDETREDMCISYAEQANWFTLLFGDP 135
Cdd:cd02964     8 GVVPVSALEGK--TVGLYFSASWCPPCRAFTPKLVEFYEKLKEEGKNFEIVFVSRDRSEESFNEYFSEMPPWLAVPFEDE 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1274108175 136 IIITLQYKH-GVTSVPHLVVTRPDGSMVSSHGILDLDEFGRNALIAW 181
Cdd:cd02964    86 ELRELLEKQfKVEGIPTLVVLKPDGDVVTTNARDEVEEDPGACAFPW 132

Tryparedoxin (TryX)-like family; composed of TryX and related proteins including nucleoredoxin (NRX), rod-derived cone viability factor (RdCVF) and the nematode homolog described as a 16-kD class of TRX. Most members of this family, except RdCVF, are protein disulfide oxidoreductases containing an active site CXXC motif, similar to TRX.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274108175  56 EKVPIEWLLDSanILVLYFSMRDSDRSDNIMSQFYEFYENARFKNLPIEVINIPMDETREDMCISYAEQANWFTLLFGDP 135
Cdd:cd02964     8 GVVPVSALEGK--TVGLYFSASWCPPCRAFTPKLVEFYEKLKEEGKNFEIVFVSRDRSEESFNEYFSEMPPWLAVPFEDE 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1274108175 136 IIITLQYKH-GVTSVPHLVVTRPDGSMVSSHGILDLDEFGRNALIAW 181
Cdd:cd02964    86 ELRELLEKQfKVEGIPTLVVLKPDGDVVTTNARDEVEEDPGACAFPW 132

Tryparedoxin (TryX)-like family; composed of TryX and related proteins including nucleoredoxin (NRX), rod-derived cone viability factor (RdCVF) and the nematode homolog described as a 16-kD class of TRX. Most members of this family, except RdCVF, are protein disulfide oxidoreductases containing an active site CXXC motif, similar to TRX.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274108175  56 EKVPIEWLLDSanILVLYFSMRDSDRSDNIMSQFYEFYENARFKNLPIEVINIPMDETREDMCISYAEQANWFTLLFGDP 135
Cdd:cd02964     8 GVVPVSALEGK--TVGLYFSASWCPPCRAFTPKLVEFYEKLKEEGKNFEIVFVSRDRSEESFNEYFSEMPPWLAVPFEDE 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1274108175 136 IIITLQYKH-GVTSVPHLVVTRPDGSMVSSHGILDLDEFGRNALIAW 181
Cdd:cd02964    86 ELRELLEKQfKVEGIPTLVVLKPDGDVVTTNARDEVEEDPGACAFPW 132

Tryparedoxin (TryX)-like family, TryX and nucleoredoxin (NRX) subfamily; TryX and NRX are thioredoxin (TRX)-like protein disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active center CXXC motif. TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyzes the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase. Vertebrate NRX is a 400-amino acid nuclear protein with one redox active TRX domain containing a CPPC active site motif followed by one redox inactive TRX-like domain. Mouse NRX transcripts are expressed in all adult tissues but is restricted to the nervous system and limb buds in embryos. Plant NRX, longer than the vertebrate NRX by about 100-200 amino acids, is a nuclear protein containing a redox inactive TRX-like domain between two redox active TRX domains. Both vertebrate and plant NRXs show thiol oxidoreductase activity in vitro. Their localization in the nucleus suggests a role in the redox regulation of nuclear proteins such as transcription factors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1274108175  53 HNYEKVPIEWLLDSaNILvLYFSMRDSDRSDNIMSQFYEFYENARFKNLPIEVINIPMDETREDMCISYAEQAnWFTLLF 132
Cdd:cd03009     6 NDGGKVPVSSLEGK-TVG-LYFSASWCPPCRAFTPKLVEFYEKLKESGKNFEIVFISWDRDEESFNDYFSKMP-WLAVPF 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1274108175 133 GD-PIIITLQYKHGVTSVPHLVVTRPDGSMVSSHGI 167
Cdd:cd03009    83 SDrERRSRLNRTFKIEGIPTLIILDADGEVVTTDAR 118