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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1083260004 210 MEKDMRSLAGLLGDKKYIMGPKLSTLDATVFGHLAQAMWTLPGTRPERLIKGELINLAMYCERI 273
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLPSPALRIHLKEYPNLVAYCERI 64

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 1083260004  46 AIILHQFaRPNNGVPSLSPFCLKMETYLRMADLPYQNYFGG--KLSAQGKMPWIEYNHEKVSGTEFIIDFLEEKLG 119
Cdd:cd03080     1 MITLYQF-PRAFGVPSLSPFCLKVETFLRMAGIPYENKFGGlaKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1083260004 134 SRAVTKMVEEHFYWTLAYcqwvdnlnetrkmlslsgggpfsnllrwvvchitkgivkremhghgigrfseeEIYMLMEKD 213
Cdd:cd03193     1 ARALSRMVETHLYWALRR-----------------------------------------------------EIYELALED 27

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1083260004 214 MRSLAGLLGDKKYIMGPKLSTLDATVFGHLAQAMWTLPGTRPERLIKGELINLAMYCERIR 274
Cdd:cd03193    28 LEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLLRVLVASSPNLVEYCERIR 88

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 1083260004  46 AIILHQFaRPNNGVPSLSPFCLKMETYLRMADLPYQNYFGG--KLSAQGKMPWIEYNHEKVSGTEFIIDFLEEKLG 119
Cdd:cd03080     1 MITLYQF-PRAFGVPSLSPFCLKVETFLRMAGIPYENKFGGlaKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1083260004 210 MEKDMRSLAGLLGDKKYIMGPKLSTLDATVFGHLAQAMWTLPGTRPERLIKGELINLAMYCERI 273
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLPSPALRIHLKEYPNLVAYCERI 64

Failed axon connections homolog N-terminus; This family represents the N-terminal domain of the failed axon connections homolog (FAXC). This protein is localized to the cellular membranes, thus it is likely that this region anchors it to the plasma membrane. It is thought to play a role in axonal development, being involved in cell-cell interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1083260004   1 MAGLGSDPWWKKTLYLTGGALLAAAAYLLHELLVIRKQQEIDSKDAIILHQFA 53
Cdd:pfam19333  52 MSALGSDSWWRKTLYLTGGALLAAAAYLLHELLAIRKEQELDSKDAIILHQFS 104

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 1083260004 151 YCQWVD--NLNETRKMlslSGGGPFSNLLRWVVCHITKGIVKREMHGHGIGRFSEEEIYMLMEKDMRSLAGLLGDKKYIM 228
Cdd:cd03211     4 YISWCDeeTYNEVTKP---RYGSVYPWPLNHILAYRKQREVLRKLKALGWSDKSLDQVFDEVEKCCQALSEKLGTNQYFF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1083260004 229 GPKLSTLDATVFGHLAQAMWT-LPGTRPERLIKGeLINLAMYCERIR 274
Cdd:cd03211    81 GDQPTELDALVFGHLFTILTTpLPNDELAAIVKK-YPNLVEFCRRIE 126

GST_N family, Metaxin subfamily, Metaxin 1-like proteins; composed of metaxins 1 and 3, and similar proteins including Tom37 from fungi. Mammalian metaxin (or metaxin 1) and the fungal protein Tom37 are components of preprotein import complexes 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1083260004  49 LHQFaRPNNGVPSLSPFCLKMETYLRMADLPYQNYFGGK--LSAQGKMPWIEYNHEKVSGTEFIIDFLEEK 117
Cdd:cd03078     3 LHVW-GGDWGLPSVDPECLAVLAYLKFAGAPLKVVPSNNpwRSPTGKLPALLTSGTKISGPEKIIEYLRKQ 72

GST_N 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 1083260004  66 CLKMETYLRMADLPYQNYFGGK---LSAQGKMPWIEYNHEKVSGTEFIIDFLEEK 117
Cdd:cd03079    20 CLAVQTFLKMCNLPFNVRCRANaefMSPSGKVPFIRVGNQIVSEFGPIVQFVEAK 74