C-terminal, alpha helical domain of microsomal Prostaglandin E synthase Type 2; Glutathione S-transferase (GST) C-terminal domain family, microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH, or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature, and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated and a C-terminal soluble domain with a GST-like structure. The C-terminal GST-like domain contains two structural domains, an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST active site is located in a cleft between the two structural domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 223 GKEARTEEMKWRQWADDWLVHLISPNVYRTPAEALASFDYIVREGKFGAVEAAMAKYVGAAAMYLISKRLKSRHHLQDDV 302
Cdd:cd03197    1 AQLADPEEKKWRKWVDDVLVHLLSPNIYRTFSEALQAFDYITTVGNFGPWERIVAKYVGAAAMYLISKRLKKKRNIKDDV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900 303 RVDLYEAANKWVTAVGKDRPFMGGQKPNLADLAVYGVLRVMEGLEAFDDLMRHSHIQPWYLRMERAIEE 371
Cdd:cd03197   81 RESLYDALNDWVKALGKKRKFHGGSKPNLADLAVYGVLRSIEGLDAFKDVLANTKIGPWYERMKEAVGS 149

C-terminal, alpha helical domain of microsomal Prostaglandin E synthase Type 2; Glutathione S-transferase (GST) C-terminal domain family, microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH, or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature, and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated and a C-terminal soluble domain with a GST-like structure. The C-terminal GST-like domain contains two structural domains, an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST active site is located in a cleft between the two structural domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 223 GKEARTEEMKWRQWADDWLVHLISPNVYRTPAEALASFDYIVREGKFGAVEAAMAKYVGAAAMYLISKRLKSRHHLQDDV 302
Cdd:cd03197    1 AQLADPEEKKWRKWVDDVLVHLLSPNIYRTFSEALQAFDYITTVGNFGPWERIVAKYVGAAAMYLISKRLKKKRNIKDDV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900 303 RVDLYEAANKWVTAVGKDRPFMGGQKPNLADLAVYGVLRVMEGLEAFDDLMRHSHIQPWYLRMERAIEE 371
Cdd:cd03197   81 RESLYDALNDWVKALGKKRKFHGGSKPNLADLAVYGVLRSIEGLDAFKDVLANTKIGPWYERMKEAVGS 149

Glutaredoxin;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 260763900  102 TLYQYKTCPFCSKVRAFLDFHSLPYQVVEV--NPVRRTEIK-FSSYRKVPILV 151
Cdd:pfam00462   2 VLYTKPTCPFCKRAKRLLKSLGVDFEEIDVdeDPEIREELKeLSGWPTVPQVF 54

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 101 LTLYQYKTCPFCSKVRAFLDFHSLPYQVVEVNPVRRTE-----IKFSSYRKVPILVaqEGDslQQLNDSSVIIsalktyl 175
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQkspefLALNPLGKVPVLV--DDG--LVLTESLAIL------- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 176 vsgqpleevityyppmkamndqgkevtefcnkywLMLDEK--EAQQMYGGKEARTEEMKWRQWADDWLVHLISPNVYRTP 253
Cdd:COG0625   71 ----------------------------------EYLAERypEPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLA 116

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 254 AEalasfdyivregkfgAVEAAMAKYVGAAAMYL--ISKRLksrhhlqddvrvdlyeaankwvtavgKDRPFMGGQKPNL 331
Cdd:COG0625  117 PE---------------KDPAAIARARAELARLLavLEARL--------------------------AGGPYLAGDRFSI 155

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 260763900 332 ADLAVYGVLRVMEGLEafDDLMRHSHIQPWYLRME 366
Cdd:COG0625  156 ADIALAPVLRRLDRLG--LDLADYPNLAAWLARLA 188

C-terminal, alpha helical domain of microsomal Prostaglandin E synthase Type 2; Glutathione S-transferase (GST) C-terminal domain family, microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH, or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature, and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated and a C-terminal soluble domain with a GST-like structure. The C-terminal GST-like domain contains two structural domains, an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST active site is located in a cleft between the two structural domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 260763900 223 GKEARTEEMKWRQWADDWLVHLISPNVYRTPAEALASFDYIVREGKFGAVEAAMAKYVGAAAMYLISKRLKSRHHLQDDV 302
Cdd:cd03197    1 AQLADPEEKKWRKWVDDVLVHLLSPNIYRTFSEALQAFDYITTVGNFGPWERIVAKYVGAAAMYLISKRLKKKRNIKDDV 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900 303 RVDLYEAANKWVTAVGKDRPFMGGQKPNLADLAVYGVLRVMEGLEAFDDLMRHSHIQPWYLRMERAIEE 371
Cdd:cd03197   81 RESLYDALNDWVKALGKKRKFHGGSKPNLADLAVYGVLRSIEGLDAFKDVLANTKIGPWYERMKEAVGS 149

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 260763900 101 LTLYQYKTCPFCSKVRAFLDFHSLPYQVVEVNPVRRTEIKF---SSYRKVPILVaqEGDslQQLNDSSVII 168
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFlalNPLGKVPVLE--DGG--LVLTESLAIL 67

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 260763900 100 QLTLYQYKTCPFCSKVRAFLDFHSLPYQVVEV--NPVRRTE-IKFSSYRKVPILV 151
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVdeDPEAREElRERSGRRTVPVIF 55

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 260763900  108 TCPFCSKVRAFLDFHSLPYQVVEV--NPVRRTE--IKFSSYRKVPILVAQEGDSlqqLNDSSVIISAL 171
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIELVdlDPKDKPPelLALNPLGTVPVLVLPDGTV---LTDSLVILEYL 65

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 260763900 101 LTLYQYKTC-------PFCSKVRAFLDFHSLPYQVVEVNPVRRteikfSSYRKVPILVaqegDSLQQLNDSSVIISALK 172
Cdd:cd03080    2 ITLYQFPRAfgvpslsPFCLKVETFLRMAGIPYENKFGGLAKR-----SPKGKLPFIE----LNGEKIADSELIIDHLE 71

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 260763900 272 VEAAMAKYVGAAAMYLISKRLKSRHH--LQDDVRVDLYEAANKWVTAVGKdRPFMGGQKPNLADLAVYGVLRVMEGL-EA 348
Cdd:cd00299    5 EDWADATLAPPLVRLLYLEKVPLPKDeaAVEAAREELPALLAALEQLLAG-RPYLAGDQFSLADVALAPVLARLEALgPY 83

                         90
                 ....*....|....*..
gi 260763900 349 FDDLMRHSHIQPWYLRM 365
Cdd:cd00299   84 YDLLDEYPRLKAWYDRL 100

Glutaredoxin 2 [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900 103 LYQYKTCPFCSKVRAFLDFHSLPYQVV------EVNPVRRTEIKfssyrKVPILVAQEG 155
Cdd:COG2999    3 LYIYDHCPFCVRARMIFGLKNIPVELIvllnddEETPIRMIGKK-----MVPILEKDDG 56

transcriptional regulator, Spx/MgsR family; This model represents a portion of the proteins within the larger set covered by pfam03960. That larger family includes a glutaredoxin-dependent arsenate reductase (TIGR00014). Characterized members of this family include Spx and MgsR from Bacillus subtili. Spx is a global regulator for response to thiol-specific oxidative stress. It interacts with RNA polymerase. MgsR (modulator of the general stress response, also called YqgZ) provides a second level of regulation for more than a third of the proteins in the B. subtilis general stress regulon controlled by Sigma-B. [Regulatory functions, DNA interactions]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900  101 LTLYQYKTCPFCSKVRAFLDFHSLPYQVVEV--NPVRRTEIKF---SSYRKVPILVAQEGDSLQQLNDS 164
Cdd:TIGR01617   1 IKVYGSPNCTTCKKARRWLEANGIEYQFIDIgeDGPTREELLDilsLLEDGIDPLLNTRGQSYRALNTS 69

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 260763900 101 LTLYQYKTCPFCSKVRAFLDFHSLPYQVVEVNPVRRTE--IKFSSYRKVPILVAQEgdslQQLNDSSVI 167
Cdd:cd03059    1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEdlAELNPYGTVPTLVDRD----LVLYESRII 65