C-terminal, alpha helical domain of Class Sigma Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma; 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  83 LEQCQADAVVDTLDDFMSLFPWAEKDQDLKERMFNELLTHQAPRLLKDLDTYLGDKEWFIGNYqVTWADFYWDICSTTLL 162
Cdd:cd10295     2 LEQCLVDALVDTLDDFMSCFPWAEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGREWLVGKS-VTWADFYWDTCSTTLL 80

                          90       100
                  ....*....|....*....|
gi 1907173178 163 VLKPGLLDIYPKLVSLRNKV 182
Cdd:cd10295    81 SFKPDLLKNYPRLVALRDKV 100

C-terminal, alpha helical domain of Class Sigma Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma; 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  83 LEQCQADAVVDTLDDFMSLFPWAEKDQDLKERMFNELLTHQAPRLLKDLDTYLGDKEWFIGNYqVTWADFYWDICSTTLL 162
Cdd:cd10295     2 LEQCLVDALVDTLDDFMSCFPWAEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGREWLVGKS-VTWADFYWDTCSTTLL 80

                          90       100
                  ....*....|....*....|
gi 1907173178 163 VLKPGLLDIYPKLVSLRNKV 182
Cdd:cd10295    81 SFKPDLLKNYPRLVALRDKV 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178   4 YKLLYFNMRGRAEIIRYIFAYLDIKYEDHRIEQADWPKIKPTL----PFGKIPVLEVEGLTIHQSLAIARYL---TKNTD 76
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFlalnPLGKVPVLVDDGLVLTESLAILEYLaerYPEPP 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  77 LAGKTALEQCQADAVVDTLD-DFM-SLFPWAEKDQDLKERMFNELLTHQAPRLLKDLDTYLGDKEWFIGNyQVTWADFYw 154
Cdd:COG0625    82 LLPADPAARARVRQWLAWADgDLHpALRNLLERLAPEKDPAAIARARAELARLLAVLEARLAGGPYLAGD-RFSIADIA- 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1907173178 155 diCSTTLLVLKPGLLDI--YPKLVSLRNKVQAIPAISAWI 192
Cdd:COG0625   160 --LAPVLRRLDRLGLDLadYPNLAAWLARLAARPAFQRAL 197

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178 106 EKDQDLKERMFNELLTHQAPRLLKDLDTYL--GDKEWFIGNyQVTWADF-YWDICSTTLLVLKPGLLDIYPKLVSLRNKV 182
Cdd:pfam14497  13 YEDEKKKAKRRKEFREERLPKFLGYFEKVLnkNGGGYLVGD-KLTYADLaLFQVLDGLLYPKAPDALDKYPKLKALHERV 91

                          90
                  ....*....|...
gi 1907173178 183 QAIPAISAWILKR 195
Cdd:pfam14497  92 AARPNIKAYLASR 104

glutathione S-transferase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907173178  25 LDIKYEDHRieQADWPKIKPtlpFGKIPVLEVEGLTIHQSLAIARYL-----TKNTDLAGKTALEQCQADAVVD 93
Cdd:PLN02395   32 VDLMKGEHK--QPEYLALQP---FGVVPVIVDGDYKIFESRAIMRYYaekyrSQGPDLLGKTIEERGQVEQWLD 100

C-terminal, alpha helical domain of Class Sigma Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma; 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  83 LEQCQADAVVDTLDDFMSLFPWAEKDQDLKERMFNELLTHQAPRLLKDLDTYLGDKEWFIGNYqVTWADFYWDICSTTLL 162
Cdd:cd10295     2 LEQCLVDALVDTLDDFMSCFPWAEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGREWLVGKS-VTWADFYWDTCSTTLL 80

                          90       100
                  ....*....|....*....|
gi 1907173178 163 VLKPGLLDIYPKLVSLRNKV 182
Cdd:cd10295    81 SFKPDLLKNYPRLVALRDKV 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907173178   4 YKLLYFNMRGRAEIIRYIFAYLDIKYEDHRIEQADWPK-IKPTLPFGKIPVLEVEGLTIHQSLAIARYL 71
Cdd:cd03076     2 YTLTYFPVRGRAEAIRLLLADQGISWEEERVTYEEWQEsLKPKMLFGQLPCFKDGDLTLVQSNAILRHL 70

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi, and Alpha. 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation. Other class Sigma-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase, and PGD2 synthase activities, and may play an important role in host-parasite interactions. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  84 EQCQADAVVDTLDDFMSLFPWA--EKDQDLKERMFNELLTHQAPRLLKDLDTYLGD--KEWFIGNyQVTWADFYWDICST 159
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYfyEPDGEEKKEKKKEFLEEALPKFLGKFEKILKKsgGGYFVGD-KLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|....
gi 1907173178 160 TLLVLKPG-LLDIYPKLVSLRNKV 182
Cdd:cd03192    81 YLLYLLPKdLLEKYPKLKALRERV 104

glutathione s-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178   3 NYKLLYFNMRGRAEIIRYIFAYLDIKYEDHR--------IEQADWPKIKPTlPFGKIPVLEVEGLTIHQSLAIARYLTKN 74
Cdd:PTZ00057    4 EIVLYYFDARGKAELIRLIFAYLGIEYTDKRfgengdafIEFKNFKKEKDT-PFEQVPILEMDNIIFAQSQAIVRYLSKK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173178  75 TDLAGKTALEQCQADAVVDTLDDFMSLFpwaeKDQDLKERMFNELLTHQAPRLLKDLDTYL--GDKEWFIGNyQVTWAD- 151
Cdd:PTZ00057   83 YKICGESELNEFYADMIFCGVQDIHYKF----NNTNLFKQNETTFLNEELPKWSGYFENILkkNHCNYFVGD-NLTYADl 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907173178 152 ----FYWDICSTTllvlkPGLLDIYPKLVSLRNKVQAIPAISAWILKRPQT 198
Cdd:PTZ00057  158 avfnLYDDIETKY-----PNSLKNFPLLKAHNEFISNLPNIKNYISNRKES 203

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 1907173178   8 YFNMRG--RAEIIRYIFAYLDIKYEDHRIEQADWPKIKPTL----PFGKIPVLEVEGLTIHQSLAIARYL 71
Cdd:pfam02798   5 LYGIRGspRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELlklnPLGKVPALEDGGKKLTESRAILEYI 74

GST_N family, Class Mu 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 class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907173178   5 KLLYFNMRGRAEIIRYIFAYLDIKYEDHRIEQAD--------WPKIKPTL--PFGKIPVLEVEGLTIHQSLAIARYLTK 73
Cdd:cd03075     2 TLGYWDIRGLAQPIRLLLEYTGEKYEEKRYELGDapdydrsqWLNEKFKLglDFPNLPYYIDGDVKLTQSNAILRYIAR 80

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Mu 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 class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1) thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907173178 125 PRLLKDLDTYLGDKEWFIGNYqVTWADF----YWDIcsttLLVLKPGLLDIYPKLVSLRNKVQAIPAISAWI 192
Cdd:cd03209    41 PDKLKLFSEFLGDRPWFAGDK-ITYVDFllyeALDQ----HRIFEPDCLDAFPNLKDFLERFEALPKISAYM 107

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
                  ....*....|....*....|....*
gi 1907173178  47 PFGKIPVLEVEGLTIHQSLAIARYL 71
Cdd:cd03042    48 PQGLVPTLVIDGLVLTQSLAIIEYL 72

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 1907173178   7 LYFNMRGRAEIIRYIFAYLDIKYEDHRIEQADWPKIKPTL----PFGKIPVLEVEGLTIHQSLAIARYL 71
Cdd:cd03046     3 LYHLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYlainPLGKVPVLVDGDLVLTESAAIILYL 71

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907173178  18 IRYIFAYLDIKYEDHRIEQAD-WPKIKPTLPFGKIPVLEVEGLTIHQSLAIARYL 71
Cdd:pfam13417  13 VRIALNEKGLPYEFVPIPPGDhPPELLAKNPLGKVPVLEDDGGILCESLAIIDYL 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907173178  20 YIFAYL-DIKYEDHRIEQADWPKIKPTL----PFGKIPVLEVEGLTIHQSLAIARYLT 72
Cdd:cd03050    16 YIFLKLnKIPFEECPIDLRKGEQLTPEFkkinPFGKVPAIVDGDFTLAESVAILRYLA 73

glutathione S-transferase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907173178  25 LDIKYEDHRieQADWPKIKPtlpFGKIPVLEVEGLTIHQSLAIARYL-----TKNTDLAGKTALEQCQADAVVD 93
Cdd:PLN02395   32 VDLMKGEHK--QPEYLALQP---FGVVPVIVDGDYKIFESRAIMRYYaekyrSQGPDLLGKTIEERGQVEQWLD 100