C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain 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. Other 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544 199 ELDEILHRDLRIVENTLAKKKFLFGEEITAADATVFSQLATVYYPFRNHIS-DVLEKDFPKLLEYCERVR 267
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLlRVLVASSPNLVEYCERIR 88

C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain 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. Other 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544 199 ELDEILHRDLRIVENTLAKKKFLFGEEITAADATVFSQLATVYYPFRNHIS-DVLEKDFPKLLEYCERVR 267
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLlRVLVASSPNLVEYCERIR 88

Glutathione S-transferase, C-terminal domain; This domain is closely related to PF00043.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17560544   205 HRDLRIVENTLAKKKFLFGEEITAADATVFSQLATVYY------PFRNHIsdvleKDFPKLLEYCERV 266
Cdd:pfam17171   2 KKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYtplpspALRIHL-----KEYPNLVAYCERI 64

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544   52 RLKNCPnlspFCMKIEILCRIFKIPYEI----ITCTSER----SRNGLVPFVELNGEHIADSDLIEMRLRSHFKIPSLPT 123
Cdd:PLN02817  69 KLGDCP----FCQRVLLTLEEKHLPYDMklvdLTNKPEWflkiSPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPLAT 144

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544  124 ELETQSVALSKFadhhlffvlirfkiavdefyktiieiiglPTFLNFLlmpllkaiigknvynKCQGAIGDFELSELDEI 203
Cdd:PLN02817 145 PPEKASVGSKIF-----------------------------STFIGFL---------------KSKDPGDGTEQALLDEL 180

                        170       180       190
                 ....*....|....*....|....*....|....
gi 17560544  204 LHRDLRIVENtlakKKFLFGEEITAADATVFSQL 237
Cdd:PLN02817 181 TSFDDYIKEN----GPFINGEKISAADLSLGPKL 210

C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain 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. Other 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544 199 ELDEILHRDLRIVENTLAKKKFLFGEEITAADATVFSQLATVYYPFRNHIS-DVLEKDFPKLLEYCERVR 267
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLlRVLVASSPNLVEYCERIR 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544    61 PFCMKIEILCRIFKIPYEIITCTSE-RSRNGLVPFVELNGEHIADSDLIEMRLRSHF--KIPSLPTELETQSVALSKFAD 137
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYEVEPSSNPsASPKGKLPFIELNGDLIADSEFIIEFLKEKGvdLDAGLSPEQKADARALKALVE 80

                          90
                  ....*....|....*..
gi 17560544   138 HHLFFVLIRFKIAVDEF 154
Cdd:pfam17172  81 EHLYWALLYERWLDPEN 97

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17560544   196 ELSELDEILHRDLRIVENTLAKKKFLFGEEITAADATVFSQLATVYYPFRNHisdVLEKDFPKLLEYCER 265
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGL---DLREGYPRLRAWLER 67

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 17560544 167 FLNFLLMPLLKAIIGKNVYNKcqgAIGDFELSELDEILHRDLRIVENTLAKKKFLFGEEITAADATVFSQLAtvyYPFRN 246
Cdd:cd00299   7 WADATLAPPLVRLLYLEKVPL---PKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLA---RLEAL 80

                        90       100
                ....*....|....*....|
gi 17560544 247 HISDVLEKDFPKLLEYCERV 266
Cdd:cd00299  81 GPYYDLLDEYPRLKAWYDRL 100

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 17560544    60 SPFCMKIEILCRIFKIPYEIITCTSERSR--------NGLVPFVELNGEHIADSDLI 108
Cdd:pfam13417   7 SPYARRVRIALNEKGLPYEFVPIPPGDHPpellaknpLGKVPVLEDDGGILCESLAI 63

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17560544 202 EILHRDLRIVENTLAKKKFLFGEEITAADAtvfsQLATVYY--PFRNHisdvLEKDFPKLLEYCERVR 267
Cdd:cd03188  45 ERLERRLAYLDAQLAGGPYLLGDQFSVADA----YLFVVLRwaRAVGL----DLSDWPHLAAYLARVA 104

C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17560544 208 LRIVENTLAKKKFLFGEEITAADATVFSQLA---TVYYP-F---RNHIsdvleKDFPKLLEY 262
Cdd:cd03190  46 LDKLEKRLSKQPYLLGDRLTEADIRLFTTLIrfdPVYHQhFkcnLKTI-----RDYPNLWRY 102

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17560544  63 CMKIEILCRIFKIPYEII--------TCTSE---RSRNGLVPFVELNGEHIADSDLI 108
Cdd:cd03056  12 CYKVRLLLALLGIPYEWVevdilkgeTRTPEflaLNPNGEVPVLELDGRVLAESNAI 68

C-terminal, alpha helical domain of Metaxin 2; Glutathione S-transferase (GST) C-terminal domain family, Metaxin subfamily, Metaxin 2; a metaxin 1 binding protein identified through a yeast two-hybrid system using metaxin 1 as the bait. Metaxin 2 shares sequence similarity with metaxin 1 but does not contain a C-terminal mitochondrial outer membrane signal-anchor domain. It associates with mitochondrial membranes through its interaction with metaxin 1, which is a component of the mitochondrial preprotein import complex of the outer membrane. The biological function of metaxin 2 is unknown. It is likely that it also plays a role in protein translocation into the mitochondria. However, this has not been experimentally validated. In a recent proteomics study, it has been shown that metaxin 2 is overexpressed in response to lipopolysaccharide-induced liver injury.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17560544 215 LAKKKFLFGEEITAADATVFSQLATV---YYPFrNHISDVLEKdFPKLLEYCERVR 267
Cdd:cd03211  73 LGTNQYFFGDQPTELDALVFGHLFTIlttPLPN-DELAAIVKK-YPNLVEFCRRIE 126