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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62472216 105 IIYLYQFSRTPLLPSLSPYCLKVETWLRLVGLKYENVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 179
Cdd:cd03080   1 MITLYQFPRAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLAKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62472216 105 IIYLYQFSRTPLLPSLSPYCLKVETWLRLVGLKYENVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 179
Cdd:cd03080   1 MITLYQFPRAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLAKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75

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 62472216 269 EIEEFGKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIayPLRDYMTEKCPNLIGHVSRMK 340
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDS--PLLRVLVASSPNLVEYCERIR 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62472216 108 LYQFSRtpllpslSPYCLKVETWLRLVGLKYENVDHKMR--------FRSK--KGQLPFIELNGEEIADSAIIIKELSsk 177
Cdd:COG0625   4 LYGSPP-------SPNSRRVRIALEEKGLPYELVPVDLAkgeqkspeFLALnpLGKVPVLVDDGLVLTESLAILEYLA-- 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62472216 178 yEKYLDSGL---TAEQRNVSYATIAMLENHLiwiifywrakypdnvlkgykvnlqHAlglrlpnSILNFFFKITFGRKGT 254
Cdd:COG0625  75 -ERYPEPPLlpaDPAARARVRQWLAWADGDL------------------------HP-------ALRNLLERLAPEKDPA 122

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62472216 255 KKLKAHgigvhsaEEIEEFgkddLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIA-YP-LRDYM 325
Cdd:COG0625 123 AIARAR-------AELARL----LAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDRLGLDLAdYPnLAAWL 184

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62472216 105 IIYLYQFSRTPLLPSLSPYCLKVETWLRLVGLKYENVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 179
Cdd:cd03080   1 MITLYQFPRAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLAKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75

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 62472216 106 IYLYQFSRTPLLPSLSPYCLKVETWLRLVGLKYENVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSK 177
Cdd:cd03054   1 LELYQWGRAFGLPSLSPECLKVETYLRMAGIPYEVVFSSNPWRSPTGKLPFLELNGEKIADSEKIIEYLKKK 72

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 62472216   274 GKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDiAYPLRDYMTEkCPNLIGHVSRM 339
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLP-SPALRIHLKE-YPNLVAYCERI 64

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 62472216 266 SAEEIEEF----GKDDLKVLSEMLDCKPFFFGDEPTTLDVVAF---AVLSQLHYLSKDIAYPLRdymteKCPNLIGHVSR 338
Cdd:cd03212  57 SEEEVEKElykdAKECLNLLSERLGEKKFFFGDRPTSLDALVFgylAPLLKAPLPNNKLQNHLK-----GCPNLVQFVDR 131

                ....*.
gi 62472216 339 MKDKCF 344
Cdd:cd03212 132 ILQNYF 137

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 62472216   121 SPYCLKVETWLRLVGLKYENVDH-------KMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 179
Cdd:pfam13417   7 SPYARRVRIALNEKGLPYEFVPIppgdhppELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYP 72

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62472216 255 KKLKAHGIGVHSAEE-IEEFGKDdLKVLSEMLDCKPFFFGDEPTTLDVVAFAVL-----SQLhyLSKDIAYPLRDYmtek 328
Cdd:cd03211  43 RKLKALGWSDKSLDQvFDEVEKC-CQALSEKLGTNQYFFGDQPTELDALVFGHLftiltTPL--PNDELAAIVKKY---- 115

                        90
                ....*....|
gi 62472216 329 cPNLIGHVSR 338
Cdd:cd03211 116 -PNLVEFCRR 124

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62472216 276 DDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDI--AYP-LRDYMT--EKCPNLIGHVSRMKDKCFP 345
Cdd:cd03209  42 DKLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQHRIFEPDCldAFPnLKDFLErfEALPKISAYMKSDRFIKWP 116