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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  82 QARARVEQWMDWQASDLNSAWRHVFMARVRQHPDYPDDARAEASLAQWNRLMGVLDAQLAASDgYVAGDTFTLADIVLGL 161
Cdd:cd03180     1 AQRALADRWMDWQTSTLNPAFRYAFWGLVRTPPEQRDPAAIAASLAACNKLMAILDAQLARQA-YLAGDRFTLADIALGC 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1405241237 162 STQRWRSTPGHKPALPHLAAWFERLRQQPGF 192
Cdd:cd03180    80 SVYRWLELPIERPALPHLERWYARLSQRPAF 110

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPLRHEPAPPADL---LAALNPNRQVPVLRDGDFVLWESNSICRYLAARAG 72
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHppeLLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYP 72

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  82 QARARVEQWMDWQASDLNSAWRHVFMARVRQHPDYPDDARAEASLAQWNRLMGVLDAQLAASDgYVAGDTFTLADIVLGL 161
Cdd:cd03180     1 AQRALADRWMDWQTSTLNPAFRYAFWGLVRTPPEQRDPAAIAASLAACNKLMAILDAQLARQA-YLAGDRFTLADIALGC 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1405241237 162 STQRWRSTPGHKPALPHLAAWFERLRQQPGF 192
Cdd:cd03180    80 SVYRWLELPIERPALPHLERWYARLSQRPAF 110

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPLRHEP----APPADLLAALNPNRQVPVLRDGDFVLWESNSICRYLA 68
Cdd:cd00570     3 LYYFPGSPRSLRVRLALEEKGLPYELVPvdlgEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPLRHEPAPPADL---LAALNPNRQVPVLRDGDFVLWESNSICRYLAARAG 72
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHppeLLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYP 72

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237   1 MLALYGKPTSINVRKVLwLC---AGLDLPLRH------EPAPPADLLAalNPNRQVPVLRDGDFVLWESNSICRYLAARA 71
Cdd:PLN02473    2 VVKVYGQIKAANPQRVL-LCfleKGIEFEVIHvdldklEQKKPEHLLR--QPFGQVPAIEDGDLKLFESRAIARYYATKY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  72 GRD--DLLPAATQARARVEQWMDWQASDLNSAWRHVFMARV-RQHPDYP-DDARAEASLAQWNRLMGVLDAQLaASDGYV 147
Cdd:PLN02473   79 ADQgtDLLGKTLEHRAIVDQWVEVENNYFYAVALPLVINLVfKPRLGEPcDVALVEELKVKFDKVLDVYENRL-ATNRYL 157

                         170
                  ....*....|
gi 1405241237 148 AGDTFTLADI 157
Cdd:PLN02473  158 GGDEFTLADL 167

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 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPlrHEPAPpADLLA---------ALNPNRQVPVLRDGDFVLWESNSICRYLA 68
Cdd:cd03056     3 LYGFPLSGNCYKVRLLLALLGIP--YEWVE-VDILKgetrtpeflALNPNGEVPVLELDGRVLAESNAILVYLA 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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1405241237   2 LALYGKPTSINVRkVLWLCAGLDLPLRHEPAP-------PADLLAaLNPNRQVPVLRDGDFVLWESNSICRYLAAR 70
Cdd:cd03046     1 ITLYHLPRSRSFR-ILWLLEELGLPYELVLYDrgpgeqaPPEYLA-INPLGKVPVLVDGDLVLTESAAIILYLAEK 74

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  83 ARARVEQWMDWQASDL-NSAWRHVFMA--RVRQHPDYPDDARAEAslaqwNRLMGVLDAQLAASdGYVAGDTFTLADIVL 159
Cdd:cd03181     1 EAAQVLQWISFANSELlPAAATWVLPLlgIAPYNKKAVDKAKEDL-----KRALGVLEEHLLTR-TYLVGERITLADIFV 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1405241237 160 GLSTQR---------WRStpghkpALPHLAAWFERLRQQPGFAE 194
Cdd:cd03181    75 ASALLRgfetvldpeFRK------KYPNVTRWFNTVVNQPKFKA 112

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1405241237   9 TSINVRKVLWLCAGLDLP-----LRHEPAPPADLLAALNPNRQVPVLRDGD-FVLWESNSICRYLAAR 70
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPyeielVDLDPKDKPPELLALNPLGTVPVLVLPDgTVLTDSLVILEYLEEL 68

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 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPLRHEPAppaDLLA---------ALNPNRQVPVLRDGDFVLWESNSICRYLAA 69
Cdd:cd03045     3 LYYLPGSPPCRAVLLTAKALGLELNLKEV---NLMKgehlkpeflKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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 1405241237   2 LALYGKPTSINVRKVLWLCAGLDLPLRHEPAP------PADLLAALNPNRQVPVLRDGDFVLWESNSICRYLAA 69
Cdd:cd03050     1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDlrkgeqLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLAR 74

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 1405241237 113 HPDYPDDARAEASLAQWNRLMGVLDAQLAaSDGYVAGDTFTLADIVLGLSTQRWRSTPGHKP--ALPHLAAWFERLRQQP 190
Cdd:pfam00043  15 PPEEKKEPEVDEALEKVARVLSALEEVLK-GQTYLVGDKLTLADIALAPALLWLYELDPACLreKFPNLKAWFERVAARP 93

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 1405241237  87 VEQWMDWQASDLNSAWRHVFMARVRqhPDYPDDARAEASLAQWNRLMGVLDAQLAAsDGYVAGDTFTLADIVLGLSTQRW 166
Cdd:cd00299     1 VRALEDWADATLAPPLVRLLYLEKV--PLPKDEAAVEAAREELPALLAALEQLLAG-RPYLAGDQFSLADVALAPVLARL 77

                          90       100
                  ....*....|....*....|...
gi 1405241237 167 RSTPGH---KPALPHLAAWFERL 186
Cdd:cd00299    78 EALGPYydlLDEYPRLKAWYDRL 100

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces 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 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. 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  84 RARVEQW---MDWQASD-LNSAWRHVfmarvrqHPDYPDD------ARAEASLAQWNRLMGVLDAQLAASDgYVAGDTFT 153
Cdd:cd03182     5 KALIEMWqrrAELQGLApVFQAFRHA-------TPGLKPDrevqvpEWGERNKKRVIDFLPVLDKRLAESP-YVAGDRFS 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1405241237 154 LADIV----LGLSTQRWRSTPghkPALPHLAAWFERLRQQPGF 192
Cdd:cd03182    77 IADITafvaLDFAKNLKLPVP---EELTALRRWYERMAARPSA 116

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 1405241237   1 MLALYGKPTSiNVRKVLWLCAGLDLPLR-----------HEPAppadlLAALNPNRQVPVLRD---GDFVLWESNSICRY 66
Cdd:cd03048     1 MITLYTHGTP-NGFKVSIMLEELGLPYEihpvdiskgeqKKPE-----FLKINPNGRIPAIVDhngTPLTVFESGAILLY 74

                  ....*..
gi 1405241237  67 LAARAGR 73
Cdd:cd03048    75 LAEKYDK 81

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  89 QWMDWQASDLNSAWRHVFMARVRQHPDYPDD-ARAEASLAQwnrLMGVLDAQLAASDgYVAGDTFTLADIVLGlSTQRWR 167
Cdd:cd03207     3 RWLFFAAGTVEPPLLNKALGRFFEPPWGEPAiAAAYGDLDE---RLAALEAALAGRP-YLVGERFSAADLLLA-SVLRWA 77

                          90       100
                  ....*....|....*....|...
gi 1405241237 168 STPGHKPALPHLAAWFERLRQQP 190
Cdd:cd03207    78 RAFGLLPEYPALRAYVARCTARP 100

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  78 PAATQARARVEQWMDW-QASDLNSAWRHVFMARVRQHP------------DYPDDARAEASLaqwNRLMGVLDAQLAaSD 144
Cdd:cd03189     2 PPDTAEYADYLYWLHFaEGSLMPPLLLKLVFGKIGEAPppffrpisrkiaDKPLQAFINPEL---KRHLDFLEDHLA-KH 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1405241237 145 GYVAGDTFTLADIVLGLSTQRWRSTPGHKPALPHLAAWFERLRQQP 190
Cdd:cd03189    78 PYFAGDELTAADIMMSFPLEAALARGPLLEQYPNIAAYLERIEARP 123

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237 102 WRHVFMArvrqHPDYPDDARAEASLAQW-----NRLMGVLDAQLAASDG-YVAGDTFTLADIVL--GLSTQRWRSTPGHK 173
Cdd:pfam14497   3 LHHPIAS----SLYYEDEKKKAKRRKEFreerlPKFLGYFEKVLNKNGGgYLVGDKLTYADLALfqVLDGLLYPKAPDAL 78

                          90       100
                  ....*....|....*....|.
gi 1405241237 174 PALPHLAAWFERLRQQPGFAE 194
Cdd:pfam14497  79 DKYPKLKALHERVAARPNIKA 99

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

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1405241237  33 PPADLlAALNPNRQVPVLRDGDFVLWESNSICRYLAAR 70
Cdd:cd03059    36 PPEDL-AELNPYGTVPTLVDRDLVLYESRIIMEYLDER 72

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 1405241237   4 LYGKPTSINVRKVLWLCA--GLDLPLR---------HEPAppadlLAALNPNRQVPVLR-DGDFVLWESNSICRYL 67
Cdd:cd03051     3 LYDSPTAPNPRRVRIFLAekGIDVPLVtvdlaageqRSPE-----FLAKNPAGTVPVLElDDGTVITESVAICRYL 73

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

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gi 1405241237   4 LYGKPTSINVRKVLWLCAGLDLPLRHEPAPPADL-----LAALNPNRQVPVLRDGD-FVLWESNSICRYLA 68
Cdd:cd03044     3 LYTYPGNPRSLKILAAAKYNGLDVEIVDFQPGKEnktpeFLKKFPLGKVPAFEGADgFCLFESNAIAYYVA 73

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1405241237  83 ARARVEQWMDWQASDLNSAWRHVFMARVRQhPDY----PDDARAEASLAQWNRLMGVLDAQLAASDGYVAGDTFTLADIV 158
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLL-PLFggtpVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLS 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1405241237 159 L-----GLSTQRWRSTPGHkpalPHLAAWFERLRQ--QPGFAE 194
Cdd:cd03183    80 AiceimQPEAAGYDVFEGR----PKLAAWRKRVKEagNPLFDE 118

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.

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gi 1405241237  46 QVPVLRDGDFVLWESNSICRYLA 68
Cdd:cd03076    49 QLPCFKDGDLTLVQSNAILRHLG 71

Thyroid peroxidase (TPO); TPO is a member of the animal heme peroxidase family, which is expressed in the thyroid and involved in the processing of iodine and iodine compounds. Specifically, TPO oxidizes iodide via hydrogen peroxide to form active iodine, which is then, for example, incorporated into the tyrosine residues of thyroglobulin to yield mono- and di-iodotyrosines.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1405241237   1 MLALYGKPTSINVrkvlWLcAGL--DLPLRHEPAPpadLLAALnPNRQVPVLRDGDFVLWESNSI 63
Cdd:cd09825   453 ILDLYKHPDNIDV----WL-GGLaeDFLPGARTGP---LFACL-IGKQMKALRDGDRFWWENSNV 508

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

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1405241237 149 GDTFTLADIVL----------GLSTQRWrsTPGhkpALPHLAAWFERLRQQPGF 192
Cdd:cd03204    63 GESFTAADISLsvllhrlkflGLSRRFW--GNG---KRPNIESYFERVRQRESF 111