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 763385725 158 EILALSRRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAILAPFFDSPLRRC-AESFPNLVAYTARMM 226
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 763385725 158 EILALSRRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAILAPFFDSPLRRC-AESFPNLVAYTARMM 226
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 763385725  164 RRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAIL-APFFDSPLRRCAESFPNLVAYTARM 225
Cdd:pfam17171   2 KKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILyTPLPSPALRIHLKEYPNLVAYCERI 64

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 763385725 158 EILALSRRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAILAPFFDSPLRRC-AESFPNLVAYTARMM 226
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 763385725  164 RRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAIL-APFFDSPLRRCAESFPNLVAYTARM 225
Cdd:pfam17171   2 KKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILyTPLPSPALRIHLKEYPNLVAYCERI 64

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 763385725   2 ITVHGSTPLFGLPVGSPYVTKTEVQLRMMGLPFTT-RNAMPTDSPKGQIPFVDDDGTRIADSHFIRVHVEEK 72
Cdd:cd03054    1 LELYQWGRAFGLPSLSPECLKVETYLRMAGIPYEVvFSSNPWRSPTGKLPFLELNGEKIADSEKIIEYLKKK 72

C-terminal, alpha helical domain of Metaxin 1, Metaxin 3, and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Metaxin subfamily, Metaxin 1-like proteins; composed of metaxins 1 and 3, and similar proteins. Mammalian metaxin (or metaxin 1) is a component of the preprotein import complex of the mitochondrial outer membrane. Metaxin extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. Like the murine gene, the human metaxin gene is located downstream to the glucocerebrosidase (GBA) pseudogene and is convergently transcribed. Inherited deficiency of GBA results in Gaucher disease, which presents many diverse clinical phenotypes. Alterations in the metaxin gene, in addition to GBA mutations, may be associated with Gaucher disease. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken, and mammals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763385725 153 RHTDEEILALSRRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAIL-APFFDSPLRRCAESFPNLVAYTARMMrQFYP 231
Cdd:cd03212   59 EEVEKELYKDAKECLNLLSERLGEKKFFFGDRPTSLDALVFGYLAPLLkAPLPNNKLQNHLKGCPNLVQFVDRIL-QNYF 137

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 763385725  10 LFGLPvGSPYVTKTEVQLRMMGLPFTTRNAMPTD---------SPKGQIPFVDDDGTRIADSHFI 65
Cdd:cd00570    3 LYYFP-GSPRSLRVRLALEEKGLPYELVPVDLGEgeqeeflalNPLGKVPVLEDGGLVLTESLAI 66

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 763385725  157 EEILALSRRSLEALSVVLGDKPYLFGDHPVGVDASAFGMLAAILAPFFDSPLRrcaESFPNLVAYTAR 224
Cdd:pfam13410   3 ERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLR---EGYPRLRAWLER 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 763385725 108 RWL--IPANFEKAF-ALLAPGIPeeARPQVRATMQDGVRKSLHgtgitrhtdeeilalsrRSLEALSVVLGDKPYLFGDH 184
Cdd:cd03188    8 EWLnfIASELHKAFgPLFYPARW--ADDALAEEVKAAARERLE-----------------RRLAYLDAQLAGGPYLLGDQ 68

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 763385725 185 PVGVDASAFGMLAaiLAPFFDSPLrrcaESFPNLVAYTARM 225
Cdd:cd03188   69 FSVADAYLFVVLR--WARAVGLDL----SDWPHLAAYLARV 103

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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 Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1) thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 763385725 166 SLEALSVVLGDKPYLFGDHPVGVDASAFGMLAA--ILAPffdsplrRCAESFPNLVAYTARM 225
Cdd:cd03209   43 KLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQhrIFEP-------DCLDAFPNLKDFLERF 97

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 763385725  22 KTEVQLRMMGLPFTTRnamPTD--------------SPKGQIPFVDDDGTRIADSHFIRVHV 69
Cdd:cd03056   14 KVRLLLALLGIPYEWV---EVDilkgetrtpeflalNPNGEVPVLELDGRVLAESNAILVYL 72