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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       11 TNVLKGAAADIALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHAEK-KNFEVMLISWDESAEDFKDYYAKMPWLAL 89
Cdd:cd03009   1 DFLLRNDGGKVPVSSLEGKTVGLYFSASWCPPCRAFTPKLVEFYEKLKESgKNFEIVFISWDRDEESFNDYFSKMPWLAV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
1I5G_A       90 PFEDRKGMEFLTTGFDVKSIPTLVGVEADsGNIITTQARTMVVKdPEAKDFPW 142
Cdd:cd03009  81 PFSDRERRSRLNRTFKIEGIPTLIILDAD-GEVVTTDARELVLE-YGADAFPF 131

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       11 TNVLKGAAADIALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHAEK-KNFEVMLISWDESAEDFKDYYAKMPWLAL 89
Cdd:cd03009   1 DFLLRNDGGKVPVSSLEGKTVGLYFSASWCPPCRAFTPKLVEFYEKLKESgKNFEIVFISWDRDEESFNDYFSKMPWLAV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
1I5G_A       90 PFEDRKGMEFLTTGFDVKSIPTLVGVEADsGNIITTQARTMVVKdPEAKDFPW 142
Cdd:cd03009  81 PFSDRERRSRLNRTFKIEGIPTLIILDAD-GEVVTTDARELVLE-YGADAFPF 131

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       21 IALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHaekKNFEVMLISWDESAEDFKDYYAKMPWLALPFEDRKGMefL 100
Cdd:COG0526  21 LSLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEY---GGVVFVGVDVDENPEAVKAFLKELGLPYPVLLDPDGE--L 95

                        90       100
                ....*....|....*....|...
1I5G_A      101 TTGFDVKSIPTLVGVEADsGNII 123
Cdd:COG0526  96 AKAYGVRGIPTTVLIDKD-GKIV 117

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       11 TNVLKGAAADIALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHAEK-KNFEVMLISWDESAEDFKDYYAKMPWLAL 89
Cdd:cd03009   1 DFLLRNDGGKVPVSSLEGKTVGLYFSASWCPPCRAFTPKLVEFYEKLKESgKNFEIVFISWDRDEESFNDYFSKMPWLAV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
1I5G_A       90 PFEDRKGMEFLTTGFDVKSIPTLVGVEADsGNIITTQARTMVVKdPEAKDFPW 142
Cdd:cd03009  81 PFSDRERRSRLNRTFKIEGIPTLIILDAD-GEVVTTDARELVLE-YGADAFPF 131

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A         28 GKTVFFYFSASWCPPSRAFTPQLIDFYKAHAEKKNFEVMLISWDESAEDFKDYYAKMP--WLALPFEDRKGMEFLTTgFD 105
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKKKKNVEIVFVSLDRDLEEFKDYLKKMPkdWLSVPFDDDERNELKRK-YG 79

                  ....*...
1I5G_A        106 VKSIPTLV 113
Cdd:pfam13905  80 VNAIPTLV 87

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       21 IALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHAeKKNFEVMLISWDES-AEDFKDYYAKMPWLALPFEDRKGMef 99
Cdd:cd02966  12 VSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYK-DDGVEVVGVNVDDDdPAAVKAFLKKYGITFPVLLDPDGE-- 88

                        90       100
                ....*....|....*....|....*...
1I5G_A      100 LTTGFDVKSIPTLVGVEADsGNIITTQA 127
Cdd:cd02966  89 LAKAYGVRGLPTTFLIDRD-GRIRARHV 115

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       20 DIALPSLAGKTVFFYFSASWCPPSRAFTPQLIDFYKAHAeKKNFEVMLISWD--ESAEDFKDyyakmpWLALPFE---DR 94
Cdd:COG1225  13 TVSLSDLRGKPVVLYFYATWCPGCTAELPELRDLYEEFK-DKGVEVLGVSSDsdEAHKKFAE------KYGLPFPllsDP 85

                        90       100
                ....*....|....*....|....*....
1I5G_A       95 KGMefLTTGFDVKSIPTLVGVEADsGNII 123
Cdd:COG1225  86 DGE--VAKAYGVRGTPTTFLIDPD-GKIR 111

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1I5G_A       26 LAGKTVFFYFSASWCPPSRAFTPQLIdfyKAHAEKKNFEVMLISWDESAEdfkdyyakmpwlalpfedrkgmefLTTGFD 105
Cdd:cd02947   8 KSAKPVVVDFWAPWCGPCKAIAPVLE---ELAEEYPKVKFVKVDVDENPE------------------------LAEEYG 60

                ....*...
1I5G_A      106 VKSIPTLV 113
Cdd:cd02947  61 VRSIPTFL 68

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                        10        20        30
                ....*....|....*....|....*....|
1I5G_A       19 ADIALPSLAGKTVFFYFSASWCPPSRAFTP 48
Cdd:cd03011  11 EQFDLESLSGKPVLVYFWATWCPVCRFTSP 40