C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551  91 PYEKAMARFWAKFIDDQILTLGFRSLVKAEKGREVAIEETRELLMFLEKE-VTGKDFFGGKTIGFLDMIAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227551 170 LWKGiGIDMIPEEKFPELNRWIKNLEEVEAVRGCIPPREKQIERMTKI 217
Cdd:cd03185  81 EEVG-GVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551  91 PYEKAMARFWAKFIDDQILTLGFRSLVKAEKGREVAIEETRELLMFLEKE-VTGKDFFGGKTIGFLDMIAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227551 170 LWKGiGIDMIPEEKFPELNRWIKNLEEVEAVRGCIPPREKQIERMTKI 217
Cdd:cd03185  81 EEVG-GVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551   9 KLLGFWASPFSRRVEMALKLKGVPYEYLEEDL---PNKTPLLLELNPLHKkVPVLVHNDKILLESHLILEYIDQTWKNSP 85
Cdd:COG0625   3 KLYGSPPSPNSRRVRIALEEKGLPYELVPVDLakgEQKSPEFLALNPLGK-VPVLVDDGLVLTESLAILEYLAERYPEPP 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551  86 ILPQDPYEKAMARFWAKFIDDQI---LTLGFRSLV--KAEKGREVAIEETRELLMFLEKEVTGKDFFGGKTIGFLDMIAg 160
Cdd:COG0625  82 LLPADPAARARVRQWLAWADGDLhpaLRNLLERLApeKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFSIADIAL- 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15227551 161 smipFCLARLWKGIGIDMipeEKFPELNRWIKNLEEVEAVRGCIPPREKQIE 212
Cdd:COG0625 161 ----APVLRRLDRLGLDL---ADYPNLAAWLARLAARPAFQRALAAAEPDLA 205

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551    9 KLLGFWASPFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELNPLhKKVPVLVHND-KILLESHLILEYIDQTWKNSPIL 87
Cdd:PRK10357   2 KLIGSYTSPFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPL-GKVPALVTEEgECWFDSPIIAEYIELLNVAPAML 80

                 ....
gi 15227551   88 PQDP 91
Cdd:PRK10357  81 PRDP 84

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551   104 IDDQILTLGFRSLVKAEKGRE----VAIEETRELLMFLEKEVTGKDFFGGKTIGFLDMIAgsmipFCLARLWKGIGIDmI 179
Cdd:pfam00043   1 LMDLRMQIALLPYVPPEEKKEpevdEALEKVARVLSALEEVLKGQTYLVGDKLTLADIAL-----APALLWLYELDPA-C 74

                          90
                  ....*....|....*..
gi 15227551   180 PEEKFPELNRWIKNLEE 196
Cdd:pfam00043  75 LREKFPNLKAWFERVAA 91

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551  91 PYEKAMARFWAKFIDDQILTLGFRSLVKAEKGREVAIEETRELLMFLEKE-VTGKDFFGGKTIGFLDMIAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227551 170 LWKGiGIDMIPEEKFPELNRWIKNLEEVEAVRGCIPPREKQIERMTKI 217
Cdd:cd03185  81 EEVG-GVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551   9 KLLGFWASPFSRRVEMALKLKGVPYEYLEEDL---PNKTPLLLELNPLHKkVPVLVHNDKILLESHLILEYIDQTWKNSP 85
Cdd:COG0625   3 KLYGSPPSPNSRRVRIALEEKGLPYELVPVDLakgEQKSPEFLALNPLGK-VPVLVDDGLVLTESLAILEYLAERYPEPP 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551  86 ILPQDPYEKAMARFWAKFIDDQI---LTLGFRSLV--KAEKGREVAIEETRELLMFLEKEVTGKDFFGGKTIGFLDMIAg 160
Cdd:COG0625  82 LLPADPAARARVRQWLAWADGDLhpaLRNLLERLApeKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFSIADIAL- 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15227551 161 smipFCLARLWKGIGIDMipeEKFPELNRWIKNLEEVEAVRGCIPPREKQIE 212
Cdd:COG0625 161 ----APVLRRLDRLGLDL---ADYPNLAAWLARLAARPAFQRALAAAEPDLA 205

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15227551    10 LLGFWASPFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELNPlHKKVPVLVHNDKILLESHLILEYIDQT 80
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNP-LGKVPVLEDDGGILCESLAIIDYLEEL 70

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15227551    15 ASPFSRRVEMALKLKGVPYEYLEEDLP--NKTPLLLELNPLHkKVPVLV-HNDKILLESHLILEYID 78
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIELVDLDpkDKPPELLALNPLG-TVPVLVlPDGTVLTDSLVILEYLE 66

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15227551  17 PFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELNPLHkKVPVLVHNDKILLESHLILEYIDQ 79
Cdd:cd03059  10 VYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYG-TVPTLVDRDLVLYESRIIMEYLDE 71

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 15227551   9 KLLGFWASPFSRRVEMALKLKGVPYEYLEEDLPN---KTPLLLELNPlHKKVPVLVHNDKILLESHLILEY 76
Cdd:cd03056   2 KLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKgetRTPEFLALNP-NGEVPVLELDGRVLAESNAILVY 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 15227551   8 VKLLGFWASPFSRRVEMALKLKGVPYEYLEEDL---PNKTPLLLELNPLhKKVPVLVHNDKILLESHLILEYID 78
Cdd:cd03053   2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLtkgEHKSPEHLARNPF-GQIPALEDGDLKLFESRAITRYLA 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15227551  15 ASPFSRRVEMALKLKGVPYEYLEEDLPNK---TPLLLELNPLHKkVPVLVHNDKILLESHLILEY 76
Cdd:cd03045   8 GSPPCRAVLLTAKALGLELNLKEVNLMKGehlKPEFLKLNPQHT-VPTLVDNGFVLWESHAILIY 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 15227551  17 PFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELNPLhKKVPVLVHN-DKILLESHLILEYID 78
Cdd:cd03055  28 PYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQ-GKVPALEIDeGKVVYESLIICEYLD 89

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. 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. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15227551   8 VKLLGFWASPFSRRVEMALKLKGVPYEYLEEDL---PNKTPLLLELNPLhKKVPVLVHNDKILLESHLILEYI 77
Cdd:cd03050   1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLrkgEQLTPEFKKINPF-GKVPAIVDGDFTLAESVAILRYL 72

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 15227551 112 GFRSLVKAEKGREVAIEETRELLMFLEKEVT--GKDFFGGKTIGFLDMiagSMIPFClARLW--KGIGIDMIPEEKFPEL 187
Cdd:cd03184  19 AFYKFLRSGEDRKGLKEELRSALENLEEELAkrGTPFFGGNSPGMVDY---MIWPWF-ERLEalKLLDGYELCLDRFPKL 94

                        90
                ....*....|....*..
gi 15227551 188 NRWIKNLEEVEAVRGCI 204
Cdd:cd03184  95 KKWMAAMKQDPAVKAFY 111

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15227551  16 SPFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELN-PLHKKVPVLVH-NDKILLESHLILEYIDQT 80
Cdd:cd03038  16 SPNVWKTRLALNHKGLEYKTVPVEFPDIPPILGELTsGGFYTVPVIVDgSGEVIGDSFAIAEYLEEA 82

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 15227551  13 FWASPFSRRVEMALKLKGVPYEYLEEDLP---NKTPLLLELNPlHKKVPVLV---HNDKILLESHLILEY 76
Cdd:cd03048   6 THGTPNGFKVSIMLEELGLPYEIHPVDISkgeQKKPEFLKINP-NGRIPAIVdhnGTPLTVFESGAILLY 74

GST_N family, unknown subfamily 2; 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. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 15227551  41 PNKTPLLLELNPlHKKVPVLVHNDKILLESHLILEYI 77
Cdd:cd03047  37 GLDTPEFLAMNP-NGRVPVLEDGDFVLWESNAILRYL 72

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551   17 PFSRRVEMALKLKGVPYEYLEEDLPNKTPLLLELNPlHKKVPVLVHNDKILLESHLILEYIDQTWKNSPI 86
Cdd:PLN02378  21 PFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISP-QGKVPVLKIDDKWVTDSDVIVGILEEKYPDPPL 89

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal TRX-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15227551  14 WASPFS-RRVEMALKLKGVPYEYLEEDLP---NKTPLLLELNPlHKKVPVLVHNDKILLESHLILEYID 78
Cdd:cd03052   6 WTQSFSsQKVRLVIAEKGLRCEEYDVSLPlseHNEPWFMRLNP-TGEVPVLIHGDNIICDPTQIIDYLE 73

GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, predominantly uncharacterized, with similarity to metaxins and GSTs. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. One characterized member of this subgroup is a novel GST from Rhodococcus with toluene o-monooxygenase and gamma-glutamylcysteine synthetase activities. Also members are the cadmium-inducible lysosomal protein CDR-1 and its homologs from C. elegans, and the failed axon connections (fax) protein from Drosophila. CDR-1 is an integral membrane protein that functions to protect against cadmium toxicity and may also have a role in osmoregulation to maintain salt balance in C. elegans. The fax gene of Drosophila was identified as a genetic modifier of Abelson (Abl) tyrosine kinase. The fax protein is localized in cellular membranes and is expressed in embryonic mesoderm and axons of the central nervous system.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15227551  15 ASPFSRRVEMALKLKGVPYEYLEEDLPNKTPlllelnplHKKVPVLVHNDKILLESHLILEYIDQTWK 82
Cdd:cd03080  16 LSPFCLKVETFLRMAGIPYENKFGGLAKRSP--------KGKLPFIELNGEKIADSELIIDHLEEKYG 75

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227551    17 PFSRRVEMALKLKGVPYEylEEDLPNktplllELNPLHKKVPVLVHNDKILLESHLILEYIDqtwKNSPILPQD--PYEK 94
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYE--VEPSSN------PSASPKGKLPFIELNGDLIADSEFIIEFLK---EKGVDLDAGlsPEQK 69

                          90
                  ....*....|..
gi 15227551    95 AMARFWAKFIDD 106
Cdd:pfam17172  70 ADARALKALVEE 81