C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550  91 PYEKAMVRFWAKFVDEQILPVGFMPLVKAEKGIDVAIEEIREMLMFLEKE-VTGKDFFGGKTIGFLDMVAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227550 170 AwECLGIDMTPEDTFPELNRWIKNLNEVEIVRECIPPKEKHIERMKKI 217
Cdd:cd03185  81 E-EVGGVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550  91 PYEKAMVRFWAKFVDEQILPVGFMPLVKAEKGIDVAIEEIREMLMFLEKE-VTGKDFFGGKTIGFLDMVAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227550 170 AwECLGIDMTPEDTFPELNRWIKNLNEVEIVRECIPPKEKHIERMKKI 217
Cdd:cd03185  81 E-EVGGVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550   9 KLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPKKSTL---LLELNPVHKkVPVLVHNDKLLSESHVILEYIDQTWNNNP 85
Cdd:COG0625   3 KLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKspeFLALNPLGK-VPVLVDDGLVLTESLAILEYLAERYPEPP 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550  86 ILPHDPYEKAMVRFWAKFVDEQILPVGFMPL-----VKAEKGIDVAIEEIREMLMFLEKEVTGKDFFGGKTIGFLDMVAG 160
Cdd:COG0625  82 LLPADPAARARVRQWLAWADGDLHPALRNLLerlapEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFSIADIALA 161

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15227550 161 SMIpfclaRAWECLGIDMTPedtFPELNRWIKNLNEVEIVRECIPPKEKHIE 212
Cdd:COG0625 162 PVL-----RRLDRLGLDLAD---YPNLAAWLARLAARPAFQRALAAAEPDLA 205

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550    9 KLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPKKSTLLLELNPVhKKVPVLVHND-KLLSESHVILEYIDQTWNNNPIL 87
Cdd:PRK10357   2 KLIGSYTSPFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPL-GKVPALVTEEgECWFDSPIIAEYIELLNVAPAML 80

                         90
                 ....*....|.
gi 15227550   88 PHDPYEKAMVR 98
Cdd:PRK10357  81 PRDPLAALRVR 91

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 15227550   108 ILPVGFMPLVKAEKG----IDVAIEEIREMLMFLEKEVTGKDFFGGKTIGFLDMVAgsmipFCLARAWECLGIDmTPEDT 183
Cdd:pfam00043   5 RMQIALLPYVPPEEKkepeVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIAL-----APALLWLYELDPA-CLREK 78

                          90
                  ....*....|...
gi 15227550   184 FPELNRWIKNLNE 196
Cdd:pfam00043  79 FPNLKAWFERVAA 91

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550  91 PYEKAMVRFWAKFVDEQILPVGFMPLVKAEKGIDVAIEEIREMLMFLEKE-VTGKDFFGGKTIGFLDMVAGSMIPFCLAR 169
Cdd:cd03185   1 PYERAQARFWAAYIDDKLFPAGRKVWAAKGEEQEKAVEEALEALKVLEEElKGGKPFFGGDTIGYLDIALGSFLGWFKAI 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 15227550 170 AwECLGIDMTPEDTFPELNRWIKNLNEVEIVRECIPPKEKHIERMKKI 217
Cdd:cd03185  81 E-EVGGVKLLDEEKFPLLAAWAERFLEREAVKEVLPDRDKLVEFLKAL 127

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550   9 KLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPKKSTL---LLELNPVHKkVPVLVHNDKLLSESHVILEYIDQTWNNNP 85
Cdd:COG0625   3 KLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKspeFLALNPLGK-VPVLVDDGLVLTESLAILEYLAERYPEPP 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550  86 ILPHDPYEKAMVRFWAKFVDEQILPVGFMPL-----VKAEKGIDVAIEEIREMLMFLEKEVTGKDFFGGKTIGFLDMVAG 160
Cdd:COG0625  82 LLPADPAARARVRQWLAWADGDLHPALRNLLerlapEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFSIADIALA 161

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15227550 161 SMIpfclaRAWECLGIDMTPedtFPELNRWIKNLNEVEIVRECIPPKEKHIE 212
Cdd:COG0625 162 PVL-----RRLDRLGLDLAD---YPNLAAWLARLAARPAFQRALAAAEPDLA 205

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15227550    10 LLGFWISPFSRRVEMALKLKGVPYEYLEEDLPKKSTLLLELNPVhKKVPVLVHNDKLLSESHVILEYIDQTWNNNP 85
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPL-GKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15227550   9 KLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPK---KSTLLLELNPVhKKVPVLVHNDKLLSESHVILEYID 78
Cdd:cd03042   2 ILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLKgeqLSPAYRALNPQ-GLVPTLVIDGLVLTQSLAIIEYLD 73

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        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15227550  17 PFSRRVEMALKLKGVPYEYLEEDLPKKSTLLLELNPVHkKVPVLVHNDKLLSESHVILEYIDQ 79
Cdd:cd03059  10 VYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYG-TVPTLVDRDLVLYESRIIMEYLDE 71

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15227550  15 ISPFSRRVEMALKLKGVPYEYLEEDLPKKSTL---LLELNPVHKkVPVLVHNDKLLSESHVILEY 76
Cdd:cd03045   8 GSPPCRAVLLTAKALGLELNLKEVNLMKGEHLkpeFLKLNPQHT-VPTLVDNGFVLWESHAILIY 71

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 15227550   9 KLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPK---KSTLLLELNPvHKKVPVLVHNDKLLSESHVILEY 76
Cdd:cd03056   2 KLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKgetRTPEFLALNP-NGEVPVLELDGRVLAESNAILVY 71

GST_N family, unknown subfamily 3; 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 15227550   9 KLLGFWISPFSRRVEMAL--KLKGVPYEYLEEDLPKKSTLLLELNPVhKKVPVLVHND-KLLSESHVILEYID 78
Cdd:cd03049   2 KLLYSPTSPYVRKVRVAAheTGLGDDVELVLVNPWSDDESLLAVNPL-GKIPALVLDDgEALFDSRVICEYLD 73

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 15227550  97 VRFWAKFVDEQILPVGF-------MPLVKAEKGIDVAIEEIREMLMFLEKEVTGKDFFGGKTIGFLDMVAGSMipfcLAR 169
Cdd:cd00299   1 VRALEDWADATLAPPLVrllylekVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPV----LAR 76

                        90       100
                ....*....|....*....|....*
gi 15227550 170 AWEcLGIDMTPEDTFPELNRWIKNL 194
Cdd:cd00299  77 LEA-LGPYYDLLDEYPRLKAWYDRL 100

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 15227550   8 VKLLGFWISPFSRRVEMALKLKGVPYEYLEEDLPK---KSTLLLELNPVhKKVPVLVHNDKLLSESHVILEYI 77
Cdd:cd03050   1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKgeqLTPEFKKINPF-GKVPAIVDGDFTLAESVAILRYL 72

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550   17 PFSRRVEMALKLKGVPYEYLEEDLPKKSTLLLELNPvHKKVPVLVHNDKLLSESHVILEYIDQTWNNNPIlpHDPYEKAM 96
Cdd:PLN02817  74 PFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISP-EGKVPVVKLDEKWVADSDVITQALEEKYPDPPL--ATPPEKAS 150

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15227550   97 V--RFWAKFvdeqilpVGFMPLVKAEKGIDVAIeeIREMLMFLEKEVTGKDFFGGKTIGFLDMVAG 160
Cdd:PLN02817 151 VgsKIFSTF-------IGFLKSKDPGDGTEQAL--LDELTSFDDYIKENGPFINGEKISAADLSLG 207

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Omega 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 Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550 126 AIEEIREMLMFLEKEVT--GKDFFGGKTIGFLDMvagSMIPFCLARAWECLGIDMT-PEDTFPELNRWIKNLNEVEIVRE 202
Cdd:cd03184  33 LKEELRSALENLEEELAkrGTPFFGGNSPGMVDY---MIWPWFERLEALKLLDGYElCLDRFPKLKKWMAAMKQDPAVKA 109

                        90
                ....*....|....*
gi 15227550 203 CIPPKEKHIERMKKI 217
Cdd:cd03184 110 FYTDPETHAEFLNSY 124

GST_N family, Metaxin subfamily; composed of metaxins and related proteins. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. Metaxin 2 binds to metaxin 1 and may also play a role in protein translocation into the mitochondria. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken and mammals. Sequence analysis suggests that all three metaxins share a common ancestry and that they possess similarity to GSTs. Also included in the subfamily are uncharacterized proteins with similarity to metaxins, including a novel GST from Rhodococcus with toluene o-monooxygenase and glutamylcysteine synthetase activities.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15227550  15 ISPFSRRVEMALKLKGVPYEYLEEDLPKKSTlllelnpvHKKVPVLVHNDKLLSESHVILEYIDQT 80
Cdd:cd03054  15 LSPECLKVETYLRMAGIPYEVVFSSNPWRSP--------TGKLPFLELNGEKIADSEKIIEYLKKK 72

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 15227550   108 ILPVGFMPLVKAEKG----IDVAIEEIREMLMFLEKEVTGKDFFGGKTIGFLDMVAgsmipFCLARAWECLGIDmTPEDT 183
Cdd:pfam00043   5 RMQIALLPYVPPEEKkepeVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIAL-----APALLWLYELDPA-CLREK 78

                          90
                  ....*....|...
gi 15227550   184 FPELNRWIKNLNE 196
Cdd:pfam00043  79 FPNLKAWFERVAA 91

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15227550    17 PFSRRVEMALKLKGVPYEYLEEDLPKKStlllelnpVHKKVPVLVHNDKLLSESHVILEYIDQTwNNNPILPHDPYEKAM 96
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYEVEPSSNPSAS--------PKGKLPFIELNGDLIADSEFIIEFLKEK-GVDLDAGLSPEQKAD 71

                          90
                  ....*....|....*
gi 15227550    97 VRFWAKFVDEQILPV 111
Cdd:pfam17172  72 ARALKALVEEHLYWA 86

GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, predominantly uncharacterized, with similarity to metaxins and GSTs. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. One characterized member of this subgroup is a novel GST from Rhodococcus with toluene o-monooxygenase and gamma-glutamylcysteine synthetase activities. Also members are the cadmium-inducible lysosomal protein CDR-1 and its homologs from C. elegans, and the failed axon connections (fax) protein from Drosophila. CDR-1 is an integral membrane protein that functions to protect against cadmium toxicity and may also have a role in osmoregulation to maintain salt balance in C. elegans. The fax gene of Drosophila was identified as a genetic modifier of Abelson (Abl) tyrosine kinase. The fax protein is localized in cellular membranes and is expressed in embryonic mesoderm and axons of the central nervous system.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15227550  15 ISPFSRRVEMALKLKGVPYEYLEEDLPKKSTlllelnpvHKKVPVLVHNDKLLSESHVILEYIDQ 79
Cdd:cd03080  16 LSPFCLKVETFLRMAGIPYENKFGGLAKRSP--------KGKLPFIELNGEKIADSELIIDHLEE 72