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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFPsREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANKYDT 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAK-GEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  81 SlTWYPTHAPAiLGQANMWLAFADGLTGSISAARLHDLFFYDFNA--EQCRARAHELLRILDEHLwaaeqNGHQWLCpAA 158
Cdd:COG0625   80 P-PLLPADPAA-RARVRQWLAWADGDLHPALRNLLERLAPEKDPAaiARARAELARLLAVLEARL-----AGGPYLA-GD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 500229633 159 APTIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:COG0625  152 RFSIADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFPsREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANKYDT 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAK-GEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  81 SlTWYPTHAPAiLGQANMWLAFADGLTGSISAARLHDLFFYDFNA--EQCRARAHELLRILDEHLwaaeqNGHQWLCpAA 158
Cdd:COG0625   80 P-PLLPADPAA-RARVRQWLAWADGDLHPALRNLLERLAPEKDPAaiARARAELARLLAVLEARL-----AGGPYLA-GD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 500229633 159 APTIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:COG0625  152 RFSIADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

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 500229633    2 ITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFPSrEHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLAN 76
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAG-PEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFPsREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANKYDT 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAK-GEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  81 SlTWYPTHAPAiLGQANMWLAFADGLTGSISAARLHDLFFYDFNA--EQCRARAHELLRILDEHLwaaeqNGHQWLCpAA 158
Cdd:COG0625   80 P-PLLPADPAA-RARVRQWLAWADGDLHPALRNLLERLAPEKDPAaiARARAELARLLAVLEARL-----AGGPYLA-GD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 500229633 159 APTIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:COG0625  152 RFSIADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

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 500229633   2 ITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLA 75
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDIL-KGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYLA 73

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDYElSGNCYKVRMLLSILKLPYTIETVEFFPSrEHKSPAFLRINPLGQLPVLRD---DDFVLRDAQAILVYLANK 77
Cdd:cd03048    1 MITLYTHG-TPNGFKVSIMLEELGLPYEIHPVDISKG-EQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEK 78

                 ...
gi 500229633  78 YDT 80
Cdd:cd03048   79 YDK 81

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 500229633   2 ITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLAN 76
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLM-KGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 500229633    4 LYDYELSGNCYKVRMLLSILKLPYTIETVeffpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANKYDTS 81
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPI----PPGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGP 74

GST_N family, Class Zeta 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 Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 500229633   2 ITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYL 74
Cdd:cd03042    1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLL-KGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72

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 500229633   2 ITLYDYELSGNCYKVRMLLSILKLPYTIETVEFFpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANKY 78
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLR-KGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 500229633   4 LYDYELSGNCYKVRMLLSILKLPYTIETVEFfPSREHKSPAFLRINPLGQLPVLR-DDDFVLRDAQAILVYL 74
Cdd:cd03051    3 LYDSPTAPNPRRVRIFLAEKGIDVPLVTVDL-AAGEQRSPEFLAKNPAGTVPVLElDDGTVITESVAICRYL 73

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. 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 thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-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. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. 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. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  95 QANMWLAFADGLTGSISAARLHdlFFY------DFNAEQCRARAHELLRILDEHLwaaeqNGHQWLCpAAAPTIADLACF 168
Cdd:cd03178    4 EVLQWLFFQMSGLGPMFGQAGH--FLYfapekiPYAIERYTDEVKRLYGVLDKRL-----SDRPYLA-GEEYSIADIALY 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 500229633 169 PYIALSDEAGV-SLLDYPAVRRWLDRVKRIPGF 200
Cdd:cd03178   76 PWTHYADLGGFaDLSEYPNVKRWLERIAARPAV 108

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 500229633 132 AHELLRILDEHLwaaEQNGhqWLCpAAAPTIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:cd10291   45 TKRLYGVLDRRL---AKSK--YLA-GDEYSIADIAIWPWVARHEWQGIDLADFPNLKRWFERLAARPAV 107

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 500229633 122 DFNAEQCRARAHELLRILDEHLwaaeqNGHQWLCpAAAPTIADLACFPYI---ALSDEAGVSLLDYPAVRRWLDR 193
Cdd:cd03196   36 EDDEEEYRAQAEEFLAELEARL-----SQHAYLF-GDRPSLADYAIFPFVrqfAHVDRDWFDASPYPNLRRWLNR 104

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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
                 ....*....|....*....|....*....|....*....|
gi 500229633 161 TIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:cd03177   66 TIADLSLVATVSTLEVVGFDLSKYPNVAAWYERLKALPPG 105

C-terminal, alpha helical domain of the Glutathione S-transferase family; Glutathione S-transferase (GST) family, C-terminal alpha helical 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). 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 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. 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, metaxins, stringent starvation protein A, and aminoacyl-tRNA synthetases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  96 ANMWLAFADG----LTGSISAARLHDLFFYDFNAEQCRARAHELLRILDEHLwaaeqNGHQWLCpAAAPTIADLACFPYI 171
Cdd:cd00299    1 VRALEDWADAtlapPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLL-----AGRPYLA-GDQFSLADVALAPVL 74

                         90       100
                 ....*....|....*....|....*.
gi 500229633 172 ALSDEAGV---SLLDYPAVRRWLDRV 194
Cdd:cd00299   75 ARLEALGPyydLLDEYPRLKAWYDRL 100

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  25 LPYTIETVEFFPSREHKSPAFLRINPLGQLPVLR-DDDFVLRDAQAILVYLANKYD--------TSLTWYPTHApailgq 95
Cdd:PRK10542  23 LDFTLVSVDLAKKRLENGDDYLAINPKGQVPALLlDDGTLLTEGVAIMQYLADSVPdrqllapvGSLSRYHTIE------ 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633  96 anmWLAFAdgltgsisAARLHDLFFYDFNA---EQCRARAHELL----RILDEHLwaaeqNGHQWLCpAAAPTIADLACF 168
Cdd:PRK10542  97 ---WLNYI--------ATELHKGFTPLFRPdtpEEYKPTVRAQLekkfQYVDEAL-----ADEQWIC-GQRFTIADAYLF 159

                        170       180       190
                 ....*....|....*....|....*....|
gi 500229633 169 PYIALSDEAGVSLLDYPAVRRWLDRVKRIP 198
Cdd:PRK10542 160 TVLRWAYAVKLNLEGLEHIAAYMQRVAERP 189

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDY-------ELSGNCYKVRMLLSILKLPYTIETVEFFpsreHKSPAflrinplGQLPVLRDDDFVLRDAQAILVY 73
Cdd:cd03080    1 MITLYQFprafgvpSLSPFCLKVETFLRMAGIPYENKFGGLA----KRSPK-------GKLPFIELNGEKIADSELIIDH 69

                 ....*.
gi 500229633  74 LANKYD 79
Cdd:cd03080   70 LEEKYG 75

GST_N family, 2 repeats of the N-terminal domain of soluble GSTs (2 GST_N) subfamily; composed of uncharacterized 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. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 500229633   1 MITLYDYELSGNCYKVRMLLSILKLPYTIETVeffPSREHKSPAFLRINPLGQLPVLRDDD--FVLRDAQAILVYLANKY 78
Cdd:cd03041    1 PLELYEFEGSPFCRLVREVLTELELDVILYPC---PKGSPKRDKFLEKGGKVQVPYLVDPNtgVQMFESADIVKYLFKTY 77

GST_N family, Class Pi 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumours.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 500229633   1 MITLYDYELSGNCYKVRMLLSILKLPYTIETVeffpSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYLANK 77
Cdd:cd03076    1 PYTLTYFPVRGRAEAIRLLLADQGISWEEERV----TYEEWQESLKPKMLFGQLPCFKDGDLTLVQSNAILRHLGRK 73

glutathione transferase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 500229633  25 LPYTIETVEFfPSREHKSPAFLRINPLGQLPVLRDDDFVLRDAQAILVYL 74
Cdd:PRK15113  31 LPFELKTVDL-DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYL 79

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 500229633  126 EQCRARAHELLRILDEHLwaaeqnGHQWLCPAAAPTIADLACFPYIALSDEAGVSLL---DYPAVRRWLDR 193
Cdd:pfam13410   3 ERAREQLRAALDALEARL------ADGPGLLGDRPTLADIALAPVLARLDAAYPGLDlreGYPRLRAWLER 67

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 500229633 126 EQCRARAHELLRILDEHLwaaeqNGHQWLCpAAAPTIADLACFPYIALSDEAGVSLLDYPAVRRWLDRVKRIPGF 200
Cdd:cd03180   42 AASLAACNKLMAILDAQL-----ARQAYLA-GDRFTLADIALGCSVYRWLELPIERPALPHLERWYARLSQRPAF 110