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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  92 EERIRVDILENQLMDNRMVLARLCYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPWFAGDKITFVDFIAYDVLERNQVFE 171
Cdd:cd03209    1 KERIRVDMLEQQAMDLRMGLIRICYSPDFEKLKPDYLEKLPDKLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQHRIFE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 113679874 172 AKCLDAFPNLKDFIARFEGLKKISDYMKTSRFLPRPMFTKM 212
Cdd:cd03209   81 PDCLDAFPNLKDFLERFEALPKISAYMKSDRFIKWPINGWK 121

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  92 EERIRVDILENQLMDNRMVLARLCYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPWFAGDKITFVDFIAYDVLERNQVFE 171
Cdd:cd03209    1 KERIRVDMLEQQAMDLRMGLIRICYSPDFEKLKPDYLEKLPDKLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQHRIFE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 113679874 172 AKCLDAFPNLKDFIARFEGLKKISDYMKTSRFLPRPMFTKM 212
Cdd:cd03209   81 PDCLDAFPNLKDFLERFEALPKISAYMKSDRFIKWPINGWK 121

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874    3 MTLGYWDIRG--LAHAIRLFLEYTDSSYEEKRYTMGDAPDYDqSQWLNEKFklgldFPNLPYLIDGSHKITQSNAILRYL 80
Cdd:pfam02798   1 MVLTLYGIRGspRAHRIRWLLAEKGVEYEIVPLDFGAGPEKS-PELLKLNP-----LGKVPALEDGGKKLTESRAILEYI 74

                  ..
gi 113679874   81 GR 82
Cdd:pfam02798  75 AR 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874   3 MTLGYWDIRGLAHAIRLFLEYTDSSYEEKRYTMGD----APDYDQsqwLNekfklgldfPN--LPYLIDGSHKITQSNAI 76
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqkSPEFLA---LN---------PLgkVPVLVDDGLVLTESLAI 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  77 LRYLGRKH---NLCGETEEERIRVDILEnQLMDN------RMVLARLcYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPW 147
Cdd:COG0625   70 LEYLAERYpepPLLPADPAARARVRQWL-AWADGdlhpalRNLLERL-APEKDPAAIARARAELARLLAVLEARLAGGPY 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 113679874 148 FAGDKITFVDFIAYDVLERNQVFEAKcLDAFPNLKDFIARFE 189
Cdd:COG0625  148 LAGDRFSIADIALAPVLRRLDRLGLD-LADYPNLAAWLARLA 188

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  92 EERIRVDILENQLMDNRMVLARLCYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPWFAGDKITFVDFIAYDVLERNQVFE 171
Cdd:cd03209    1 KERIRVDMLEQQAMDLRMGLIRICYSPDFEKLKPDYLEKLPDKLKLFSEFLGDRPWFAGDKITYVDFLLYEALDQHRIFE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 113679874 172 AKCLDAFPNLKDFIARFEGLKKISDYMKTSRFLPRPMFTKM 212
Cdd:cd03209   81 PDCLDAFPNLKDFLERFEALPKISAYMKSDRFIKWPINGWK 121

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874   3 MTLGYWDIRGLAHAIRLFLEYTDSSYEEKRYTMGDAPDYDqsqwlnekFKLGLDFPNLPYLIDGSHKITQSNAILRYLGR 82
Cdd:cd03039    1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELD--------LKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  104 LMDNRMVLARLCYNADFEKLKPGYLEQLPGMMRLYSEF---LGKRPWFAGDKITFVDFIAYDVLERNQVFEAKCL-DAFP 179
Cdd:pfam00043   1 LMDLRMQIALLPYVPPEEKKEPEVDEALEKVARVLSALeevLKGQTYLVGDKLTLADIALAPALLWLYELDPACLrEKFP 80

                          90
                  ....*....|..
gi 113679874  180 NLKDFIARFEGL 191
Cdd:pfam00043  81 NLKAWFERVAAR 92

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi, and Alpha. 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation. Other class Sigma-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase, and PGD2 synthase activities, and may play an important role in host-parasite interactions. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  92 EERIRVDILENQLMDNRMVLARLCYNAD----FEKLKPGYLEQLPGMMRLYSEFLGK--RPWFAGDKITFVDFIAYDVLE 165
Cdd:cd03192    1 EEEARVDAIVDTIADLRAEFAPYFYEPDgeekKEKKKEFLEEALPKFLGKFEKILKKsgGGYFVGDKLTWADLALFDVLD 80

                         90       100
                 ....*....|....*....|....
gi 113679874 166 RNQVFEAKC-LDAFPNLKDFIARF 188
Cdd:cd03192   81 YLLYLLPKDlLEKYPKLKALRERV 104

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 113679874   3 MTLGYWDIRGLAHAIRLFLEYTDSSYEEKRYTMGDAPDydqsqwlnEKFKLGLDFPNLPYLIDGSHKITQSNAILRYL 80
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQ--------EEFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi 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. Class Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 113679874  91 EEERIRVDILENQLMDNRMVLARLCYNaDFEKLKPGYLEQLPGMMRLYSEFL---GKRPWFAGDKITFVDFIAYDVLERN 167
Cdd:cd03210    1 EKEAALIDMVNDGVEDLRLKYVRMIYQ-NYEAGKDDYIKDLPEQLKPFEKLLaknNGKGFIVGDKISFADYNLFDLLDIH 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 113679874 168 QVFEAKCLDAFPNLKDFIARFEGLKKISDYMKTSRFLPRP 207
Cdd:cd03210   80 LVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

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 113679874  94 RIRVDILENQLMD--NRMVLARLCYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPWFAGDKITFVDFIAYDVLERNQVFE 171
Cdd:cd00299    2 RALEDWADATLAPplVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALG 81

                         90
                 ....*....|....*...
gi 113679874 172 AKC--LDAFPNLKDFIAR 187
Cdd:cd00299   82 PYYdlLDEYPRLKAWYDR 99

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 113679874 112 ARLCYNADFEKLKPGYLEQLPGMMRLYSEFLGKRPWFAGDKITFVDFIAYdVLERNQVFEAKCLDAFPNLKDFIAR 187
Cdd:cd03188   28 ARWADDALAEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVADAYLF-VVLRWARAVGLDLSDWPHLAAYLAR 102

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 113679874  139 SEFLGKRPWFAGDKITFVD-----FIA--YDVLERNQVFeAKCLDAFPNLKDFIAR 187
Cdd:pfam17171   9 SERLGDKPFFFGDKPTSLDalvfgHLAliLYTPLPSPAL-RIHLKEYPNLVAYCER 63

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 113679874 139 SEFLGKRPWFAGDKITFVD-----FIA--YDVLERNQVFEAKcLDAFPNLKDFIARF 188
Cdd:cd03193   32 STLLGDKKFLFGDKPTSVDatvfaHLAsiLYPPEDSPLLRVL-VASSPNLVEYCERI 87