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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13124345  22 ATLYQQLKGEQILLSDNAASLAVQAFLQMCNLPIKVVCRANAEYMSPSGKVPFIHVGNQVVSELGPIVQFVKAK 95
Cdd:cd03079   1 AALYQPYEEEQILLPDNASCLAVQTFLKMCNLPFNVRCRANAEFMSPSGKVPFIRVGNQIVSEFGPIVQFVEAK 74

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13124345  22 ATLYQQLKGEQILLSDNAASLAVQAFLQMCNLPIKVVCRANAEYMSPSGKVPFIHVGNQVVSELGPIVQFVKAK 95
Cdd:cd03079   1 AALYQPYEEEQILLPDNASCLAVQTFLKMCNLPFNVRCRANAEFMSPSGKVPFIRVGNQIVSEFGPIVQFVEAK 74

Outer mitochondrial membrane transport complex protein; The TOM37 protein is one of the outer membrane proteins that make up the TOM complex for guiding cytosolic mitochondrial beta-barrel proteins from the cytosol across the outer mitochondrial membrane into the intra-membrane space. In conjunction with TOM70 it guides peptides without an MTS into TOM40, the protein that forms the passage through the outer membrane. It has homology with Metaxin-1, also part of the outer mitochondrial membrane beta-barrel protein transport complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13124345    41 SLAVQAFLQMCNLP--IKVVCRANAEyMSPSGKVPFIHVGN-QVVSELGPIVQFVKAK--GHSLSDGLEEVQKAEMKAYM 115
Cdd:pfam10568   1 CLAAIAYLKLLALPapFEVVPSNNPD-LSPTGELPALIDGDgTWVSGFDSIVEYLRSKggGYDLDADLSAKQKADSLAYI 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 13124345   116 ELVNNMLLTAELYLQWCDEATVGEITHARYGSPYPWPLNHILAYQKQ 162
Cdd:pfam10568  80 SLLESKLYPLLLYSLWVDEENYEEVTRPAYSKLLPFPLNYILPLKYR 126

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13124345  22 ATLYQQLKGEQILLSDNAASLAVQAFLQMCNLPIKVVCRANAEYMSPSGKVPFIHVGNQVVSELGPIVQFVKAK 95
Cdd:cd03079   1 AALYQPYEEEQILLPDNASCLAVQTFLKMCNLPFNVRCRANAEFMSPSGKVPFIRVGNQIVSEFGPIVQFVEAK 74

Outer mitochondrial membrane transport complex protein; The TOM37 protein is one of the outer membrane proteins that make up the TOM complex for guiding cytosolic mitochondrial beta-barrel proteins from the cytosol across the outer mitochondrial membrane into the intra-membrane space. In conjunction with TOM70 it guides peptides without an MTS into TOM40, the protein that forms the passage through the outer membrane. It has homology with Metaxin-1, also part of the outer mitochondrial membrane beta-barrel protein transport complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13124345    41 SLAVQAFLQMCNLP--IKVVCRANAEyMSPSGKVPFIHVGN-QVVSELGPIVQFVKAK--GHSLSDGLEEVQKAEMKAYM 115
Cdd:pfam10568   1 CLAAIAYLKLLALPapFEVVPSNNPD-LSPTGELPALIDGDgTWVSGFDSIVEYLRSKggGYDLDADLSAKQKADSLAYI 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 13124345   116 ELVNNMLLTAELYLQWCDEATVGEITHARYGSPYPWPLNHILAYQKQ 162
Cdd:pfam10568  80 SLLESKLYPLLLYSLWVDEENYEEVTRPAYSKLLPFPLNYILPLKYR 126

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 13124345 179 LDQVLEDVDQCCQALSQRLGTQPYFFNKQPTELDALVFGHLYTILTTQLTNDELSEKVKNYSNLLAFCRRI 249
Cdd:cd03193  17 RREIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDSPLLRVLVASSPNLVEYCERI 87

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 13124345  22 ATLYQqLKGEQILLSDNAASLAVQAFLQMCNLPIKVVCRANAEyMSPSGKVPFIHVGNQVVSELGPIVQFVKAK 95
Cdd:cd03054   1 LELYQ-WGRAFGLPSLSPECLKVETYLRMAGIPYEVVFSSNPW-RSPTGKLPFLELNGEKIADSEKIIEYLKKK 72

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13124345  41 SLAVQAFLQMCNLPIKVVCRANAEY-------MSPSGKVPFIHVGNQVVSELGPIVQFV 92
Cdd:cd00570  12 SLRVRLALEEKGLPYELVPVDLGEGeqeeflaLNPLGKVPVLEDGGLVLTESLAILEYL 70

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13124345   179 LDQVLEDVDQCCQALSQRLGTQPYFFNKQPTELDALVFGHLYTILTTQLTNDELSEkvknYSNLLAFCRR 248
Cdd:pfam13410   2 LERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREG----YPRLRAWLER 67