GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 members include the class II insect GSTs, S-crystallins from cephalopods 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. Also members are 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1941244142  30 YTLFYFNVKALAEPLRFLFAYGGIEYEDVRVTRDEWPA--LKPTMPMGQMPVLEVDGKRVHQSISMARYLAK 99
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPEldLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 members include the class II insect GSTs, S-crystallins from cephalopods 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. Also members are 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1941244142  30 YTLFYFNVKALAEPLRFLFAYGGIEYEDVRVTRDEWPA--LKPTMPMGQMPVLEVDGKRVHQSISMARYLAK 99
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPEldLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

glutathione s-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941244142  32 LFYFNVKALAEPLRFLFAYGGIEYEDVR--VTRDEWPALK-----PTMPMGQMPVLEVDGKRVHQSISMARYLAKQVNLS 104
Cdd:PTZ00057    7 LYYFDARGKAELIRLIFAYLGIEYTDKRfgENGDAFIEFKnfkkeKDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941244142 105 GADPWEDLQIDIVVDTINDFRLKIAVVSYEPEDEikekkmITLVNEVIPFYLEKLETIVKDNNGHFALG-KLTWADIYFA 183
Cdd:PTZ00057   87 GESELNEFYADMIFCGVQDIHYKFNNTNLFKQNE------TTFLNEELPKWSGYFENILKKNHCNYFVGdNLTYADLAVF 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1941244142 184 GILDYLNYMCKKDLiENYPGLKALVESVYAIDAIKAWMEKR 224
Cdd:PTZ00057  161 NLYDDIETKYPNSL-KNFPLLKAHNEFISNLPNIKNYISNR 200

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 1941244142  29 SYTLFYFNVKALAEPLRFLFAYGGIEYEDVRVT----RDEWPALKPTMPMGQMPVLEVDGKRVHQSISMARYLAK 99
Cdd:pfam02798   2 VLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDfgagPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 members include the class II insect GSTs, S-crystallins from cephalopods 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. Also members are 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1941244142  30 YTLFYFNVKALAEPLRFLFAYGGIEYEDVRVTRDEWPA--LKPTMPMGQMPVLEVDGKRVHQSISMARYLAK 99
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPEldLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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 1941244142  29 SYTLFYFNVKALAEPLRFLFAYGGIEYEDVRVTRDEWP-ALKPTMPMGQMPVLEVDGKRVHQSISMARYLAK 99
Cdd:cd03076     1 PYTLTYFPVRGRAEAIRLLLADQGISWEEERVTYEEWQeSLKPKMLFGQLPCFKDGDLTLVQSNAILRHLGR 72

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 1941244142  30 YTLFYFNVKALAEPLRFLFAYGGIEYEDVRVTRDEWP--ALKPTMPMGQMPVLEVDGKRVHQSISMARYLA 98
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEqeEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 1941244142 121 INDFRLKIAVVSYEPEDEIKE---KKMITLVNEVIPFYLEKLEtivkdNNGHFALGKLTWADIYFAGILDYLNYMCKKDL 197
Cdd:pfam00043   1 LMDLRMQIALLPYVPPEEKKEpevDEALEKVARVLSALEEVLK-----GQTYLVGDKLTLADIALAPALLWLYELDPACL 75

                          90
                  ....*....|....*...
gi 1941244142 198 IENYPGLKALVESVYAID 215
Cdd:pfam00043  76 REKFPNLKAWFERVAARP 93

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 1941244142 108 PWEDLQIDIVVDTINDFRLKIAVvsYEPEDEIKEKKMITLVNEVIPFYLEKLETIVKDNNghFALGK-LTWADIYFAGIL 186
Cdd:cd10295     1 ELEQCLVDALVDTLDDFMSCFPW--AEKKQDVKEKMFNEALTGPAPHLLKDLDTYLGGRE--WLVGKsVTWADFYWDTCS 76

                          90       100
                  ....*....|....*....|....*
gi 1941244142 187 DYLNYMcKKDLIENYPGLKALVESV 211
Cdd:cd10295    77 TTLLSF-KPDLLKNYPRLVALRDKV 100

GST_N family, Class Alpha 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 Alpha subfamily is composed of eukaryotic GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1941244142  32 LFYFNVKALAEPLRFLFAYGGIEYEDVRV-TRDEWPALKP--TMPMGQMPVLEVDGKRVHQSISMARYLAKQVNL 103
Cdd:cd03077     4 LHYFNGRGRMESIRWLLAAAGVEFEEKFIeSAEDLEKLKKdgSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNL 78

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1941244142 110 EDLQIDIVVDTINDFRLKIAVVSYEPE-DEIKEKKMITLvneviPFYLEKLETIVKDNngHFALG-KLTWADIYFAGILD 187
Cdd:cd03209     2 ERIRVDMLEQQAMDLRMGLIRICYSPDfEKLKPDYLEKL-----PDKLKLFSEFLGDR--PWFAGdKITYVDFLLYEALD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1941244142 188 YLNYMcKKDLIENYPGLKALVESVYAIDAIKAWME-KRPVT 227
Cdd:cd03209    75 QHRIF-EPDCLDAFPNLKDFLERFEALPKISAYMKsDRFIK 114

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1941244142  44 LRFLFAYGGIEYEDVRV------TR-DEWPALKPtmpMGQMPVLEVDGKRVHQSISMARYLA 98
Cdd:cd03056    15 VRLLLALLGIPYEWVEVdilkgeTRtPEFLALNP---NGEVPVLELDGRVLAESNAILVYLA 73

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1941244142  52 GIEYEDVRVTRDEW----PALKPTMPMGQMPVLEVDGKRVHQSISMARYLAKQ 100
Cdd:cd03046    22 GLPYELVLYDRGPGeqapPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEK 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1941244142  44 LRFLFAYGGIEYEDVRV--TRDEW--PALKPTMPMGQMPVLEVDGKRVHQSISMARYL 97
Cdd:cd03042    15 VRIALNLKGLDYEYVPVnlLKGEQlsPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72