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 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGEDRLF-AMNPAGRTPVIRetDKGLVLSDSRAICEYFE 73
Cdd:cd00570    3 LYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFlALNPLGKVPVLE--DGGLVLTESLAILEYLA 71

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 496104824  11 PFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIrETDKGLVLSDSRAICEYFE 73
Cdd:PRK10357  10 PFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPLGKVPAL-VTEEGECWFDSPIIAEYIE 71

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 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGEDRLF-AMNPAGRTPVIRetDKGLVLSDSRAICEYFE 73
Cdd:cd00570    3 LYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFlALNPLGKVPVLE--DGGLVLTESLAILEYLA 71

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGE---DRLFAMNPAGRTPVIrETDKGLVLSDSRAICEYFE 73
Cdd:cd03051    3 LYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEqrsPEFLAKNPAGTVPVL-ELDDGTVITESVAICRYLE 74

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 496104824    5 YQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIRetDKGLVLSDSRAICEYFEETVD 77
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLE--DDGGILCESLAIIDYLEELYP 72

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 496104824  11 PFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIrETDKGLVLSDSRAICEYFE 73
Cdd:PRK10357  10 PFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPLGKVPAL-VTEEGECWFDSPIIAEYIE 71

GST_N 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 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIrETDKGLVLSDSRAICEY 71
Cdd:cd03055   21 LYSMRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPAL-EIDEGKVVYESLIICEY 87

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 496104824    3 HIYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGEDR---LFAMNPAGRTPVIreTDKGLVLSDSRAICEYFEE 74
Cdd:pfam02798   4 TLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKspeLLKLNPLGKVPAL--EDGGKKLTESRAILEYIAR 76

GST_N family, Class Tau 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 496104824  11 PFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPA-GRTPVIRETDKglVLSDSRAICEYFEET 75
Cdd:cd03058   10 PFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPVhKKIPVLLHNGK--PICESLIIVEYIDEA 73

GST_N family, Class Delta and Epsilon 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. 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. The class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYELQTARPWEGE---DRLFAMNPAGRTPVIRetDKGLVLSDSRAICEY 71
Cdd:cd03045    3 LYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEhlkPEFLKLNPQHTVPTLV--DNGFVLWESHAILIY 71

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing 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 N-terminal TRX-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 496104824  11 PFSRKVRLLMAEKGIAYELQTARPWEGEDR---LFAMNPAGRTPVIRETD-KGLVLSDSRAICEYFEETVDR 78
Cdd:cd03048   10 PNGFKVSIMLEELGLPYEIHPVDISKGEQKkpeFLKINPNGRIPAIVDHNgTPLTVFESGAILLYLAEKYDK 81

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496104824  10 CPFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIRETDKGlvLSDSRAICEYFEETVDRYPLisGTAQQR 89
Cdd:PLN02817  73 CPFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDEKW--VADSDVITQALEEKYPDPPL--ATPPEK 148

                 ...
gi 496104824  90 AEI 92
Cdd:PLN02817 149 ASV 151

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 496104824  10 CPFSRKVRLLMAEKGIAYELQTARPWEGEDRLFAMNPAGRTPVIRETDKGlvLSDSRAICEYFEEtvdRYP 80
Cdd:PLN02378  20 CPFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKW--VTDSDVIVGILEE---KYP 85

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496104824   8 PLCPFSRKVRLLMAEKGIAYELQTARPWEGEDR---LFAMNPAGRTPVIRETDkgLVLSDSRAICEYFEEtvdRYP---- 80
Cdd:PLN02395   8 PAFASPKRALVTLIEKGVEFETVPVDLMKGEHKqpeYLALQPFGVVPVIVDGD--YKIFESRAIMRYYAE---KYRsqgp 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496104824  81 -LISGTAQQRAEIRRLIAMFDENFYNDVSGPLLLERMKKRLVFrqAPDAKALRESMKLAHDYLDYIDYLIDNRPWLAGAT 159
Cdd:PLN02395  83 dLLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFASKMGF--PADEKVIKESEEKLAKVLDVYEARLSKSKYLAGDF 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 496104824 160 MTladLAAAAQLSVADYLGGLDWSSH-----EQARGWYLVMKSRPSFRPLLS 206
Cdd:PLN02395 161 VS---LADLAHLPFTEYLVGPIGKAYlikdrKHVSAWWDDISSRPAWKEVLA 209

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20
                 ....*....|....*....|....*
gi 496104824   4 IYQFPLCPFSRKVRLLMAEKGIAYE 28
Cdd:COG0695    4 LYTTPGCPYCARAKRLLDEKGIPYE 28

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496104824  20 MAEKGIAYELQTARPWEGEDR---LFAMNPAGRTPVIRETDkgLVLSDSRAICEYFEEtvdRYP------LISGTAQQRA 90
Cdd:PRK15113  26 LQEKGLPFELKTVDLDAGEHLqptYQGYSLTRRVPTLQHDD--FELSESSAIAEYLEE---RFAppawerIYPADLQARA 100

                 ....*..
gi 496104824  91 EIRRLIA 97
Cdd:PRK15113 101 RARQIQA 107