C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170  84 EQEATFLDMLFDAIRDVRLKYIRYVYFDEGSREDMVNKTLPESLERLECQFEIH-PGDFIIGNKLSYTDYILFEELDIYH 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17563170 163 VLDGKILDKFPALKAFWERMWQRPNLKPYLEKRTKDNVWISAVEKG 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170  84 EQEATFLDMLFDAIRDVRLKYIRYVYFDEGSREDMVNKTLPESLERLECQFEIH-PGDFIIGNKLSYTDYILFEELDIYH 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17563170 163 VLDGKILDKFPALKAFWERMWQRPNLKPYLEKRTKDNVWISAVEKG 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170    98 RDVRLKYIRYVYFDEGS-----REDMVNKTLPESLERLECQFEIHPGDFIIGNKLSYTDYILFEELD-IYHVLDGKILDK 171
Cdd:pfam14497   1 HDLHHPIASSLYYEDEKkkakrRKEFREERLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDgLLYPKAPDALDK 80

                          90       100
                  ....*....|....*....|....
gi 17563170   172 FPALKAFWERMWQRPNLKPYLEKR 195
Cdd:pfam14497  81 YPKLKALHERVAARPNIKAYLASR 104

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170   5 KLYYFSIRGYGEYIRLLLIDNGIKFE--DIRFPWQSNEWAELKKTMKFGQVPCYKVDGQEIVQAGAIMRHLGRVH---KL 79
Cdd:COG0625   3 KLYGSPPSPNSRRVRIALEEKGLPYElvPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYpepPL 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170  80 NGSNEQE-ATFLDMLFDAIRDVR--LKYIRYVYFDEGSREDM--VNKTLPESLERLECQFEihPGDFIIGNKLSYTDYIL 154
Cdd:COG0625  83 LPADPAArARVRQWLAWADGDLHpaLRNLLERLAPEKDPAAIarARAELARLLAVLEARLA--GGPYLAGDRFSIADIAL 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 17563170 155 FEELDiYHVLDGKILDKFPALKAFWERMWQRPNLKPYLEKRTKD 198
Cdd:COG0625 161 APVLR-RLDRLGLDLADYPNLAAWLARLAARPAFQRALAAAEPD 203

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170  84 EQEATFLDMLFDAIRDVRLKYIRYVYFDEGSREDMVNKTLPESLERLECQFEIH-PGDFIIGNKLSYTDYILFEELDIYH 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 17563170 163 VLDGKILDKFPALKAFWERMWQRPNLKPYLEKRTKDNVWISAVEKG 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

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 17563170   4 PKLYYFSIRGYGEYIRLLLIDNGIKFEDIRFPWQSNEWAELKKTMKFGQVPCYKVDGQEIVQAGAIMRHLGR 75
Cdd:cd03039   1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170    6 LYYFSIRGYGEYIRLLLIDNGIKFEDIRFPWQSNEWAELK-----KTMKFGQVPCYKVDGQEIVQAGAIMRHLGRVHKLN 80
Cdd:PTZ00057   7 LYYFDARGKAELIRLIFAYLGIEYTDKRFGENGDAFIEFKnfkkeKDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170   81 GSNEQEATFLDMLFDAIRDVRLKYIRYVYFDEgSREDMVNKTLPESLERLECQFEIHPGDFIIGNKLSYTDYILFEELDI 160
Cdd:PTZ00057  87 GESELNEFYADMIFCGVQDIHYKFNNTNLFKQ-NETTFLNEELPKWSGYFENILKKNHCNYFVGDNLTYADLAVFNLYDD 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 17563170  161 YHVLDGKILDKFPALKAFWERMWQRPNLKPYLEKRtKDNVW 201
Cdd:PTZ00057 166 IETKYPNSLKNFPLLKAHNEFISNLPNIKNYISNR-KESVY 205

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 17563170   4 PKLYYFSIRGYGEYIRLLLIDNGIKFEDIRFPWQSNEWAELKKTMKFGQVPCYKVDGQEIVQAGAIMRHL 73
Cdd:cd00570   1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYL 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 17563170  85 QEATFLDMLFDAIRDVRLKYIRYVYFDEGS-----REDMVNKTLPESLERLECQFEIHPGDFIIGNKLSYTDYILFEELD 159
Cdd:cd03192   1 EEEARVDAIVDTIADLRAEFAPYFYEPDGEekkekKKEFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALFDVLD 80

                        90       100
                ....*....|....*....|....
gi 17563170 160 IYHVLDGK-ILDKFPALKAFWERM 182
Cdd:cd03192  81 YLLYLLPKdLLEKYPKLKALRERV 104

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 17563170   4 PKLYYFSIRGYGEYIRLLLIDNGIKFEDiRFPWQSNEWAELKK--TMKFGQVPCYKVDGQEIVQAGAIMRHLGRVHKL 79
Cdd:cd03077   2 PVLHYFNGRGRMESIRWLLAAAGVEFEE-KFIESAEDLEKLKKdgSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNL 78

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17563170   4 PKLYYFSIRGYGEYIRLLLIDNGIKFEDIRF-----PW-QSNEWAELKKTMK--FGQVPCYKVDGQEIVQAGAIMRHLGR 75
Cdd:cd03075   1 PTLGYWDIRGLAQPIRLLLEYTGEKYEEKRYelgdaPDyDRSQWLNEKFKLGldFPNLPYYIDGDVKLTQSNAILRYIAR 80

                ..
gi 17563170  76 VH 77
Cdd:cd03075  81 KH 82

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17563170 121 KTLPESLERLECQFeIHPGDFIIGNKLSYTDYILFEELDIYHVLDGKILDKFPALKAFWERMWQRPN 187
Cdd:cd03183  48 ENLEESLDLLENKF-LKDKPFLAGDEISIADLSAICEIMQPEAAGYDVFEGRPKLAAWRKRVKEAGN 113

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 17563170 139 GDFIIGNKLSYTDYILFEELDIYhvLDGKILDKFPALKAFWERMWQRP 186
Cdd:cd03207  55 RPYLVGERFSAADLLLASVLRWA--RAFGLLPEYPALRAYVARCTARP 100