C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 111 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 190
Cdd:cd10303    1 PDLQDAYIAKQKRLKSKLLDHDNIKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGEFFSLADVSLAVTLHRL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 966959030 191 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 221
Cdd:cd10303   81 KFLGLARRNWGNGKRPNLETYYERVLKRKTF 111

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 111 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 190
Cdd:cd10303    1 PDLQDAYIAKQKRLKSKLLDHDNIKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGEFFSLADVSLAVTLHRL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 966959030 191 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 221
Cdd:cd10303   81 KFLGLARRNWGNGKRPNLETYYERVLKRKTF 111

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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 TRX-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.

                         10        20        30
                 ....*....|....*....|....*....|
gi 966959030   1 MRLNSTGEVPVLIHGENIICEATQIIDYLE 30
Cdd:cd03052   44 MRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73

Glutathione S-transferase, N-terminal domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 966959030    2 RLNSTGEVPVLIHGENIICEATQIIDYLEQTF 33
Cdd:pfam13417  40 AKNPLGKVPVLEDDGGILCESLAIIDYLEELY 71

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966959030   93 RSQIGNTESELKKL---AEENpDLQEAYIAKQKRLKSKLLDHDNVKY--LKKILDELEKVLDQVETELQRRNEE 161
Cdd:TIGR04523 116 KEQKNKLEVELNKLekqKKEN-KKNIDKFLTEIKKKEKELEKLNNKYndLKKQKEELENELNLLEKEKLNIQKN 188

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 111 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 190
Cdd:cd10303    1 PDLQDAYIAKQKRLKSKLLDHDNIKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGEFFSLADVSLAVTLHRL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 966959030 191 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 221
Cdd:cd10303   81 KFLGLARRNWGNGKRPNLETYYERVLKRKTF 111

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1-like 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1-like 1 (GDAP1L1) subfamily; GDAP1L1 is a paralogue of GDAP1 with about 56% sequence identity and 70% similarity. It's function is unknown. Like GDAP1, it does not exhibit GST activity using standard substrates. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 111 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 190
Cdd:cd10302    1 PQLTEPYLSKQKKLMAKILEHDNVNYLKKILGELAMVLDQIEAELEKRKLEYEGQKCELWLCGCIFTLADVLLGATLHRL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 966959030 191 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 221
Cdd:cd10302   81 KFLGLSKKYWEDGSRPNLQSFFERVQKRYAF 111

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) 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 TRX-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.

                         10        20        30
                 ....*....|....*....|....*....|
gi 966959030   1 MRLNSTGEVPVLIHGENIICEATQIIDYLE 30
Cdd:cd03052   44 MRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966959030  137 LKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFArRNWgNGKRPNLETYYER 214
Cdd:pfam13410   2 LERAREQLRAALDALEARL----------ADGPGLLGDRPTLADIALAPVLARLDAAYPG-LDL-REGYPRLRAWLER 67

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 131 HDNVKylKKILDELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLET 210
Cdd:cd03188   36 AEEVK--AAARERLERRLAYLDAQLAGG----------PYLLGDQFSVADAYLFVVLRWARAVGLDLSDW-----PHLAA 98

                         90
                 ....*....|....*
gi 966959030 211 YYERVLKRKTFNKVL 225
Cdd:cd03188   99 YLARVAARPAVQAAL 113

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Delta and Epsilon subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 130 DHDNVKYLKKILDELEKVLdqvetelqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLE 209
Cdd:cd03177   36 PEEKLDKLEEALEFLETFL-----------------EGSDYVAGDQLTIADLSLVATVSTLEVVGFDLSKY-----PNVA 93

                 ....*...
gi 966959030 210 TYYERVLK 217
Cdd:cd03177   94 AWYERLKA 101

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 966959030  135 KYLKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFarrNWGNGKRPNLETYYER 214
Cdd:pfam00043  22 PEVDEALEKVARVLSALEEVL----------KGQTYLVGDKLTLADIALAPALLWLYELDP---ACLREKFPNLKAWFER 88

                  ....
gi 966959030  215 VLKR 218
Cdd:pfam00043  89 VAAR 92

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 137 LKKILDELEKVLDQVETE-LQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGfaRRNWGNgkRPNLETYYERV 215
Cdd:cd03183   43 VKKAEENLEESLDLLENKfLKDK----------PFLAGDEISIADLSAICEIMQPEAAG--YDVFEG--RPKLAAWRKRV 108

                 ...
gi 966959030 216 LKR 218
Cdd:cd03183  109 KEA 111

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030  135 KYLKKILDELEKVLdqvetelqrrneetpEEGQQPWLCGESFTLADVSLAVTLHRLKFLGFARRnwgNGKRPNLETYYER 214
Cdd:pfam14497  29 ERLPKFLGYFEKVL---------------NKNGGGYLVGDKLTYADLALFQVLDGLLYPKAPDA---LDKYPKLKALHER 90

                  ....
gi 966959030  215 VLKR 218
Cdd:pfam14497  91 VAAR 94

Glutathione S-transferase, N-terminal domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 966959030    2 RLNSTGEVPVLIHGENIICEATQIIDYLEQTF 33
Cdd:pfam13417  40 AKNPLGKVPVLEDDGGILCESLAIIDYLEELY 71

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966959030 133 NVKYLKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFARRnwgNGKRPNLETYY 212
Cdd:cd03187   39 DEAVVEENEAKLKKVLDVYEARL----------SKSKYLAGDSFTLADLSHLPNLHYLMATPSKKL---FDSRPHVKAWW 105

                         90
                 ....*....|...
gi 966959030 213 ERVLKRKTFNKVL 225
Cdd:cd03187  106 EDISARPAWKKVL 118

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966959030 141 LDELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGFARRNwgngKRPNLETYYERVLKR 218
Cdd:cd03178   42 TDEVKRLYGVLDKRLSDR----------PYLAGEEYSIADIALYPWTHYADLGGFADLS----EYPNVKRWLERIAAR 105

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 966959030 147 VLDQVETELQRRNEETPEegqQPWLCGESFTLADVSLavtlhrlkflgFARRNWGNG------KRPNLETYYERVLKR 218
Cdd:PRK10542 125 VRAQLEKKFQYVDEALAD---EQWICGQRFTIADAYL-----------FTVLRWAYAvklnleGLEHIAAYMQRVAER 188

GST_N family, Class Tau 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 plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20
                 ....*....|....*....|....*..
gi 966959030   7 GEVPVLIHGENIICEATQIIDYLEQTF 33
Cdd:cd03058   48 KKIPVLLHNGKPICESLIIVEYIDEAW 74