C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735 108 YERARQKMLLELFCKVPPLSKECLialRCGRDCTDLKVALRQELCNMEEILEYQNTTFFGGDCISMIDYLVWPWFERLDV 187
Cdd:cd03184     1 YEKAQQKMLIERFSKVPSAFYKFL---RSGEDRKGLKEELRSALENLEEELAKRGTPFFGGNSPGMVDYMIWPWFERLEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1720395735 188 YGLA----DCVNHTPMLRLWIASMKQDPAVCALHTDKSVFLGFLNLY 230
Cdd:cd03184    78 LKLLdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735 108 YERARQKMLLELFCKVPPLSKECLialRCGRDCTDLKVALRQELCNMEEILEYQNTTFFGGDCISMIDYLVWPWFERLDV 187
Cdd:cd03184     1 YEKAQQKMLIERFSKVPSAFYKFL---RSGEDRKGLKEELRSALENLEEELAKRGTPFFGGNSPGMVDYMIWPWFERLEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1720395735 188 YGLA----DCVNHTPMLRLWIASMKQDPAVCALHTDKSVFLGFLNLY 230
Cdd:cd03184    78 LKLLdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVININLKS---KPDWYYTKHPFGQIPVLENSQcQLVYESVIACEYLDDVYPGR 100
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDG-LVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735 101 KLFPYDPYERARQKMLLELF-CKVPPLSKECLIALRCGRDcTDLKVALRQELCNMEEILEYQ--NTTFFGGDCISMIDYL 177
Cdd:COG0625    81 PLLPADPAARARVRQWLAWAdGDLHPALRNLLERLAPEKD-PAAIARARAELARLLAVLEARlaGGPYLAGDRFSIADIA 159

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1720395735 178 VWPWFERLDVYGLAdcVNHTPMLRLWIASMKQDPAV 213
Cdd:COG0625   160 LAPVLRRLDRLGLD--LADYPNLAAWLARLAARPAF 193

stringent starvation protein A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735  23 VIRIYSMRFCPYSHRARLVLKAKGIRHEVININLKSKPDWYYTKHPFGQIPVLENSQCQLvYESVIACEYLDDVYPGRKL 102
Cdd:PRK09481   10 VMTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTL-YESRIIMEYLDERFPHPPL 88

                          90
                  ....*....|....*
gi 1720395735 103 FPYDPYERARQKMLL 117
Cdd:PRK09481   89 MPVYPVARGESRLMM 103

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVINI 54
Cdd:COG0695     2 VTLYTTPGCPYCARAKRLLDEKGIPYEEIDV 32

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Omega subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735 108 YERARQKMLLELFCKVPPLSKECLialRCGRDCTDLKVALRQELCNMEEILEYQNTTFFGGDCISMIDYLVWPWFERLDV 187
Cdd:cd03184     1 YEKAQQKMLIERFSKVPSAFYKFL---RSGEDRKGLKEELRSALENLEEELAKRGTPFFGGNSPGMVDYMIWPWFERLEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1720395735 188 YGLA----DCVNHTPMLRLWIASMKQDPAVCALHTDKSVFLGFLNLY 230
Cdd:cd03184    78 LKLLdgyeLCLDRFPKLKKWMAAMKQDPAVKAFYTDPETHAEFLNSY 124

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVININLKS---KPDWYYTKHPFGQIPVLENSQcQLVYESVIACEYLDDVYPGR 100
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDG-LVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735 101 KLFPYDPYERARQKMLLELF-CKVPPLSKECLIALRCGRDcTDLKVALRQELCNMEEILEYQ--NTTFFGGDCISMIDYL 177
Cdd:COG0625    81 PLLPADPAARARVRQWLAWAdGDLHPALRNLLERLAPEKD-PAAIARARAELARLLAVLEARlaGGPYLAGDRFSIADIA 159

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1720395735 178 VWPWFERLDVYGLAdcVNHTPMLRLWIASMKQDPAV 213
Cdd:COG0625   160 LAPVLRRLDRLGLD--LADYPNLAAWLARLAARPAF 193

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVININLKSKPDWYYTK-HPFGQIPVLENSQCQLvYESVIACEYLD 94
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLAlNPLGKVPVLEDGGLVL-TESLAILEYLA 71

GST_N family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720395735  23 VIRIYSMRFCPYSHRARLVLKAKGIRHEVININLKS---KPDWYYTKHPFGQIPVLENSQCQLvYESVIACEYLDD 95
Cdd:cd03053     1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKgehKSPEHLARNPFGQIPALEDGDLKL-FESRAITRYLAE 75

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720395735  23 VIRIYSMRFCPYSHRARLVLKAKGIRHEVININLKSKPD---WYYTKHPFGQIPVLE-NSQCqlVYESVIACEYLDD 95
Cdd:pfam02798   2 VLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEkspELLKLNPLGKVPALEdGGKK--LTESRAILEYIAR 76

stringent starvation protein A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735  23 VIRIYSMRFCPYSHRARLVLKAKGIRHEVININLKSKPDWYYTKHPFGQIPVLENSQCQLvYESVIACEYLDDVYPGRKL 102
Cdd:PRK09481   10 VMTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTL-YESRIIMEYLDERFPHPPL 88

                          90
                  ....*....|....*
gi 1720395735 103 FPYDPYERARQKMLL 117
Cdd:PRK09481   89 MPVYPVARGESRLMM 103

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720395735  26 IYSMRFCPYSHRARLVLKAKGIRHEVININLKSKPDWYYTKHPFGQIPVLENSQCQLVYESV 87
Cdd:cd03060     3 LYSFRRCPYAMRARMALLLAGITVELREVELKNKPAEMLAASPKGTVPVLVLGNGTVIEESL 64

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395735  23 VIRIYS--MRFCPYSHRARLVLKAKGIRHEVININLKSK----PDwYYTKHPFGQIPVLENSQCQLVYESVIaCEYLDDV 96
Cdd:PRK15113    5 AITLYSdaHFFSPYVMSAFVALQEKGLPFELKTVDLDAGehlqPT-YQGYSLTRRVPTLQHDDFELSESSAI-AEYLEER 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720395735  97 YPG---RKLFPYDPYERARQKM--------LLEL---------FC--KVPPLSKE 129
Cdd:PRK15113   83 FAPpawERIYPADLQARARARQiqawlrsdLMPLreerptdvvFAgaKKAPLSEA 137

GST_N family, unknown subfamily 3; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720395735  33 PYSHRARLVL--KAKGIRHEVININLKSKPDWYYTKHPFGQIPVLENSQCQLVYESVIACEYLD 94
Cdd:cd03049    10 PYVRKVRVAAheTGLGDDVELVLVNPWSDDESLLAVNPLGKIPALVLDDGEALFDSRVICEYLD 73

Glutaredoxin;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVINI 54
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDV 31

GST_N family, unknown subfamily 4; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720395735  24 IRIYSMRFCPYSHRARLVLKAKGIRHEVININL---KSKPDWYYTKHPFGQIPVLENSQCQLVyESVIACEYL 93
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDIlkgETRTPEFLALNPNGEVPVLELDGRVLA-ESNAILVYL 72

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1720395735  23 VIRIYSMRFCPYSHRARLVLKAKGIRHEVININ 55
Cdd:cd02066     1 KVVVFSKSTCPYCKRAKRLLESLGIEFEEIDIL 33

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720395735  35 SHRARLVLKAKGIRHEVININLK---SKPDWYYTKHPFGQIPVLENSQcQLVYESVIACEYLDDVYP 98
Cdd:cd03046    11 SFRILWLLEELGLPYELVLYDRGpgeQAPPEYLAINPLGKVPVLVDGD-LVLTESAAIILYLAEKYG 76

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1720395735  26 IYSMRFCPYSHRARLVLKAKGIRHEVININ 55
Cdd:cd03419     4 VFSKSYCPYCKRAKSLLKELGVKPAVVELD 33