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 808354733   8 LTTLPRTVTVPYYAPSCLFLETFLRSKLIPYETTQCSLYNVLPREHLyPLIDVDGYFFKNLMEGLDYLLAK 78
Cdd:cd03054    3 LYQWGRAFGLPSLSPECLKVETYLRMAGIPYEVVFSSNPWRSPTGKL-PFLELNGEKIADSEKIIEYLKKK 72

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 808354733   8 LTTLPRTVTVPYYAPSCLFLETFLRSKLIPYETTQCSLYNVLPREHLyPLIDVDGYFFKNLMEGLDYLLAK 78
Cdd:cd03054    3 LYQWGRAFGLPSLSPECLKVETYLRMAGIPYEVVFSSNPWRSPTGKL-PFLELNGEKIADSEKIIEYLKKK 72

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 808354733 165 RKEVACRTEAMLEALASLLASNKYFFDvNEPSWLDCKAFAVLAQFKYTPLQNEARVKQFMKDrtPNLMTFVTRMK 239
Cdd:cd03193   17 RREIYELALEDLEALSTLLGDKKFLFG-DKPTSVDATVFAHLASILYPPEDSPLLRVLVASS--PNLVEYCERIR 88

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 808354733   8 LTTLPRTVTVPYYAPSCLFLETFLRSKLIPYETTQCSLYNVLPREHLyPLIDVDGYFFKNLMEGLDYLLAK 78
Cdd:cd03054    3 LYQWGRAFGLPSLSPECLKVETYLRMAGIPYEVVFSSNPWRSPTGKL-PFLELNGEKIADSEKIIEYLKKK 72

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 808354733 165 RKEVACRTEAMLEALASLLASNKYFFDvNEPSWLDCKAFAVLAQFKYTPLQNEARVKQFMKDrtPNLMTFVTRMK 239
Cdd:cd03193   17 RREIYELALEDLEALSTLLGDKKFLFG-DKPTSVDATVFAHLASILYPPEDSPLLRVLVASS--PNLVEYCERIR 88

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 808354733 134 QLYFWRNWIVP-QMQKRTRRRVRG-YGISGKSARKEVacRTEAMLEA------LASLLASNKYFFDvNEPSWLDCKAFAV 205
Cdd:cd03212   25 ALPFPLNFYYPgRYQRRAKDRLQLlRGLSELDSEEEV--EKELYKDAkeclnlLSERLGEKKFFFG-DRPTSLDALVFGY 101

                         90       100       110
                 ....*....|....*....|....*....|...
gi 808354733 206 LAQFKYTPLQNeARVKQFMKdRTPNLMTFVTRM 238
Cdd:cd03212  102 LAPLLKAPLPN-NKLQNHLK-GCPNLVQFVDRI 132

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 808354733 135 LYFWRNWivpQMQKRTRRRVRGYGISGKSaRKEVACRTEAMLEALASLLASNKYFFDvNEPSWLDCKAFAVLAQFKYTPL 214
Cdd:cd03211   29 LNHILAY---RKQREVLRKLKALGWSDKS-LDQVFDEVEKCCQALSEKLGTNQYFFG-DQPTELDALVFGHLFTILTTPL 103

                         90       100
                 ....*....|....*....|....*.
gi 808354733 215 QNE---ARVKQFmkdrtPNLMTFVTR 237
Cdd:cd03211  104 PNDelaAIVKKY-----PNLVEFCRR 124