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 392890098  39 VVYLYQFPrPANRQPNLSPYCLKIETFLRANRIKHEVVGTWLTlRQSPRGLLPFIELNGQQISDSQVIVWKLQKHFD 115
Cdd:cd03080    1 MITLYQFP-RAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLA-KRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 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 392890098  39 VVYLYQFPrPANRQPNLSPYCLKIETFLRANRIKHEVVGTWLTlRQSPRGLLPFIELNGQQISDSQVIVWKLQKHFD 115
Cdd:cd03080    1 MITLYQFP-RAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLA-KRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 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 392890098 194 VAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYRQQISDLLEDDFPRVRAYCDRIR 265
Cdd:cd03193   17 RREIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLLRVLVASSPNLVEYCERIR 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890098  42 LYQFPRpanrqpnlSPYCLKIETFLRANRIKHEVVGTWLT---------LRQSPRGLLPFIELNGQQISDSQVIVWKLQK 112
Cdd:COG0625    4 LYGSPP--------SPNSRRVRIALEEKGLPYELVPVDLAkgeqkspefLALNPLGKVPVLVDDGLVLTESLAILEYLAE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890098 113 HFDlDDKLEGSD---RGTARAVERMIDLSTNYALlvdktvnnahlllarqvsnlplpsfltnylakgfsQTARKRVNGVL 189
Cdd:COG0625   76 RYP-EPPLLPADpaaRARVRQWLAWADGDLHPAL-----------------------------------RNLLERLAPEK 119

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392890098 190 GKLDVAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYrqqisDLleDDFPRVRAYCDRIRQH 267
Cdd:COG0625  120 DPAAIARARAELARLLAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDRLGL-----DL--ADYPNLAAWLARLAAR 190

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 392890098  39 VVYLYQFPrPANRQPNLSPYCLKIETFLRANRIKHEVVGTWLTlRQSPRGLLPFIELNGQQISDSQVIVWKLQKHFD 115
Cdd:cd03080    1 MITLYQFP-RAFGVPSLSPFCLKVETFLRMAGIPYENKFGGLA-KRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 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 392890098 194 VAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYRQQISDLLEDDFPRVRAYCDRIR 265
Cdd:cd03193   17 RREIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLLRVLVASSPNLVEYCERIR 88

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392890098  202 RRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYR-QQISDLLEdDFPRVRAYCDRI 264
Cdd:pfam17171   2 KKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLPsPALRIHLK-EYPNLVAYCERI 64

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890098  194 VAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYRQQIsdllEDDFPRVRAYCDR 263
Cdd:pfam13410   2 LERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDL----REGYPRLRAWLER 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 392890098 167 SFLTNYLAKGFSQ-TARKRVNGVLGKLDVAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDCSVFGQIGAVFYLPYrqq 245
Cdd:cd00299    6 DWADATLAPPLVRlLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGP--- 82

                         90
                 ....*....|....*....
gi 392890098 246 iSDLLEDDFPRVRAYCDRI 264
Cdd:cd00299   83 -YYDLLDEYPRLKAWYDRL 100

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392890098 212 LGDKKFLFGDRITSVDCSVFGQIGAVFYLPY-----RQQISDLleddfPRVRAYCDRIRQHYY 269
Cdd:cd03212   80 LGEKKFFFGDRPTSLDALVFGYLAPLLKAPLpnnklQNHLKGC-----PNLVQFVDRILQNYF 137

GST_N family; microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated, and a C-terminal soluble domain with a GST-like structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890098  40 VYLYQFprpanrqpNLSPYCLKIETFLRANRIKHEVVGT---------WLTLRQSPRgLLPFIELNGQQISDSQVIVWKL 110
Cdd:cd03040    2 ITLYQY--------KTCPFCCKVRAFLDYHGIPYEVVEVnpvsrkeikWSSYKKVPI-LRVESGGDGQQLVDSSVIISTL 72

                 ...
gi 392890098 111 QKH 113
Cdd:cd03040   73 KTY 75

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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 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 three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392890098 193 DVAEQKELLRRDIRAIDDILGDKKFLFGDRITSVDC---SVFGQIGAvfylpyrqqiSDLLEdDFPRVRAYCDRIRQ 266
Cdd:cd03207   33 AIAAAYGDLDERLAALEAALAGRPYLVGERFSAADLllaSVLRWARA----------FGLLP-EYPALRAYVARCTA 98