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Conserved domains on  [gi|28574891|ref|NP_788514|]
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failed axon connections, isoform B [Drosophila melanogaster]

Protein Classification

glutathione S-transferase family protein( domain architecture ID 12182488)

glutathione S-transferase (GST) family protein such as Arabidopsis thaliana mitochondrial outer membrane import complex protein metaxin, which is involved in transport of proteins into the mitochondrion

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
GST_C_Metaxin cd03193
C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase ...
 136-207 7.18e-22

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.


:

Pssm-ID: 198302 [Multi-domain]  Cd Length: 88  Bit Score: 86.91  E-value: 7.18e-22
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28574891 136 EIEEFGKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIayPLRDYMTEKCPNLIGHVSRMK 207
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDS--PLLRVLVASSPNLVEYCERIR 88
GST_N_4 pfam17172
Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.
 11-83 6.09e-19

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.


:

Pssm-ID: 465370 [Multi-domain]  Cd Length: 97  Bit Score: 79.54  E-value: 6.09e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28574891    11 FRSKKGQLPFIELNGEEIADSAIIIKELSSKYEKyLDSGLTAEQRNVSYATIAMLENHLIWIIFYWRAKYPDN 83
Cdd:pfam17172  26 SASPKGKLPFIELNGDLIADSEFIIEFLKEKGVD-LDAGLSPEQKADARALKALVEEHLYWALLYERWLDPEN 97
 
Name Accession Description Interval E-value
GST_C_Metaxin cd03193
C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase ...
 136-207 7.18e-22

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.


Pssm-ID: 198302 [Multi-domain]  Cd Length: 88  Bit Score: 86.91  E-value: 7.18e-22
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28574891 136 EIEEFGKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIayPLRDYMTEKCPNLIGHVSRMK 207
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDS--PLLRVLVASSPNLVEYCERIR 88
GST_C_6 pfam17171
Glutathione S-transferase, C-terminal domain; This domain is closely related to PF00043.
 141-206 1.47e-19

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


Pssm-ID: 465369  Cd Length: 64  Bit Score: 80.27  E-value: 1.47e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 28574891   141 GKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDiAYPLRDYMTEkCPNLIGHVSRM 206
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLP-SPALRIHLKE-YPNLVAYCERI 64
GST_N_4 pfam17172
Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.
 11-83 6.09e-19

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.


Pssm-ID: 465370 [Multi-domain]  Cd Length: 97  Bit Score: 79.54  E-value: 6.09e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28574891    11 FRSKKGQLPFIELNGEEIADSAIIIKELSSKYEKyLDSGLTAEQRNVSYATIAMLENHLIWIIFYWRAKYPDN 83
Cdd:pfam17172  26 SASPKGKLPFIELNGDLIADSEFIIEFLKEKGVD-LDAGLSPEQKADARALKALVEEHLYWALLYERWLDPEN 97
GST_N_Metaxin_like cd03080
GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, ...
 4-43 1.36e-12

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.


Pssm-ID: 239378 [Multi-domain]  Cd Length: 75  Bit Score: 61.87  E-value: 1.36e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 28574891   4 NVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 43
Cdd:cd03080  36 NKFGGLAKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75
GstA COG0625
Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];
145-192 1.04e-03

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


Pssm-ID: 440390 [Multi-domain]  Cd Length: 205  Bit Score: 39.49  E-value: 1.04e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 28574891 145 LKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIA-YP-LRDYM 192
Cdd:COG0625 135 LAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDRLGLDLAdYPnLAAWL 184
 
Name Accession Description Interval E-value
GST_C_Metaxin cd03193
C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase ...
 136-207 7.18e-22

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.


Pssm-ID: 198302 [Multi-domain]  Cd Length: 88  Bit Score: 86.91  E-value: 7.18e-22
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28574891 136 EIEEFGKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIayPLRDYMTEKCPNLIGHVSRMK 207
Cdd:cd03193  19 EIYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPPEDS--PLLRVLVASSPNLVEYCERIR 88
GST_C_6 pfam17171
Glutathione S-transferase, C-terminal domain; This domain is closely related to PF00043.
 141-206 1.47e-19

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


Pssm-ID: 465369  Cd Length: 64  Bit Score: 80.27  E-value: 1.47e-19
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 28574891   141 GKDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDiAYPLRDYMTEkCPNLIGHVSRM 206
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLALILYTPLP-SPALRIHLKE-YPNLVAYCERI 64
GST_N_4 pfam17172
Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.
 11-83 6.09e-19

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.


Pssm-ID: 465370 [Multi-domain]  Cd Length: 97  Bit Score: 79.54  E-value: 6.09e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 28574891    11 FRSKKGQLPFIELNGEEIADSAIIIKELSSKYEKyLDSGLTAEQRNVSYATIAMLENHLIWIIFYWRAKYPDN 83
Cdd:pfam17172  26 SASPKGKLPFIELNGDLIADSEFIIEFLKEKGVD-LDAGLSPEQKADARALKALVEEHLYWALLYERWLDPEN 97
GST_N_Metaxin_like cd03080
GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, ...
 4-43 1.36e-12

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.


Pssm-ID: 239378 [Multi-domain]  Cd Length: 75  Bit Score: 61.87  E-value: 1.36e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 28574891   4 NVDHKMRFRSKKGQLPFIELNGEEIADSAIIIKELSSKYE 43
Cdd:cd03080  36 NKFGGLAKRSPKGKLPFIELNGEKIADSELIIDHLEEKYG 75
GST_C_Metaxin1_3 cd03212
C-terminal, alpha helical domain of Metaxin 1, Metaxin 3, and similar proteins; Glutathione ...
 133-211 2.42e-07

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.


Pssm-ID: 198321 [Multi-domain]  Cd Length: 137  Bit Score: 48.78  E-value: 2.42e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28574891 133 SAEEIEEF----GKDDLKVLSEMLDCKPFFFGDEPTTLDVVAF---AVLSQLHYLSKDIAYPLRdymteKCPNLIGHVSR 205
Cdd:cd03212  57 SEEEVEKElykdAKECLNLLSERLGEKKFFFGDRPTSLDALVFgylAPLLKAPLPNNKLQNHLK-----GCPNLVQFVDR 131


                ....*.
gi 28574891 206 MKDKCF 211
Cdd:cd03212 132 ILQNYF 137
GST_N_Metaxin cd03054
GST_N family, Metaxin subfamily; composed of metaxins and related proteins. Metaxin 1 is a ...
 11-41 1.62e-06

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.


Pssm-ID: 239352 [Multi-domain]  Cd Length: 72  Bit Score: 44.91  E-value: 1.62e-06
                        10        20        30
                ....*....|....*....|....*....|.
gi 28574891  11 FRSKKGQLPFIELNGEEIADSAIIIKELSSK 41
Cdd:cd03054  42 WRSPTGKLPFLELNGEKIADSEKIIEYLKKK 72
GST_C_Metaxin2 cd03211
C-terminal, alpha helical domain of Metaxin 2; Glutathione S-transferase (GST) C-terminal ...
 102-205 4.19e-06

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.


Pssm-ID: 198320  Cd Length: 126  Bit Score: 44.95  E-value: 4.19e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28574891 102 NSILNFffkitfgRKWFQGTKKLKAHGIGVHSAEE-IEEFGKDdLKVLSEMLDCKPFFFGDEPTTLDVVAFAVL-----S 175
Cdd:cd03211  30 NHILAY-------RKQREVLRKLKALGWSDKSLDQvFDEVEKC-CQALSEKLGTNQYFFGDQPTELDALVFGHLftiltT 101

                        90       100       110
                ....*....|....*....|....*....|
gi 28574891 176 QLhyLSKDIAYPLRDYmtekcPNLIGHVSR 205
Cdd:cd03211 102 PL--PNDELAAIVKKY-----PNLVEFCRR 124
GST_C_2 pfam13410
Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.
 142-192 1.40e-05

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


Pssm-ID: 433185 [Multi-domain]  Cd Length: 67  Bit Score: 41.92  E-value: 1.40e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 28574891   142 KDDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQL----HYLSKDIAYP-LRDYM 192
Cdd:pfam13410  10 RAALDALEARLADGPGLLGDRPTLADIALAPVLARLdaayPGLDLREGYPrLRAWL 65
GstA COG0625
Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];
145-192 1.04e-03

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


Pssm-ID: 440390 [Multi-domain]  Cd Length: 205  Bit Score: 39.49  E-value: 1.04e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 28574891 145 LKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDIA-YP-LRDYM 192
Cdd:COG0625 135 LAVLEARLAGGPYLAGDRFSIADIALAPVLRRLDRLGLDLAdYPnLAAWL 184
GST_C_Mu cd03209
C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione ...
 143-212 1.90e-03

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.


Pssm-ID: 198318 [Multi-domain]  Cd Length: 121  Bit Score: 37.23  E-value: 1.90e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 28574891 143 DDLKVLSEMLDCKPFFFGDEPTTLDVVAFAVLSQLHYLSKDI--AYP-LRDYMT--EKCPNLIGHVSRMKDKCFP 212
Cdd:cd03209  42 DKLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQHRIFEPDCldAFPnLKDFLErfEALPKISAYMKSDRFIKWP 116
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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