Arsenate Reductase (ArsC) family, Spx subfamily; Spx is a unique RNA polymerase (RNAP)-binding protein present in bacilli and some mollicutes. It inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP, disrupting complex formation between RNAP and certain transcriptional activator proteins like ResD and ComA. In response to oxidative stress, Spx can also activate transcription, making it a general regulator that exerts both positive and negative control over transcription initiation. Spx has been shown to exert redox-sensitive transcriptional control over genes like trxA (TRX) and trxB (TRX reductase), genes that function in thiol homeostasis. This redox-sensitive activity is dependent on the presence of a CXXC motif, present in some members of the Spx subfamily, that acts as a thiol/disulfide switch. Spx has also been shown to repress genes in a sulfate-dependent manner independent of the presence of the CXXC motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNVNVESMPLQDLY 80
Cdd:cd03032     1 MIKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKEELKEILSLTENGVEDIISTRSKAFKNLNIDIDELSLSELI 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1150403695  81 RLINEHPGLLRRPIIIDEKRLQVGYNEDEIRRFLP 115
Cdd:cd03032    81 RLISEHPSLLRRPIIIDEKRLQIGYNEDEIRQFLP 115

Arsenate reductase or related protein, glutaredoxin family [Inorganic ion transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNVNVESMPLQDLY 80
Cdd:COG1393     1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTPPTAEELKELLAKLGLGVEELLNTRGTTYRELGLKDKALSEEEAL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1150403695  81 RLINEHPGLLRRPIIIDEKRLQVGYNEDEIRRFLP 115
Cdd:COG1393    81 ALMLEHPSLIKRPIVVTGDKALVGFPPEEVLALLG 115

Uxx-star family glutaredoxin-like (seleno)protein; A number of proteins with glutaredoxin-like folds, a length of about 75 amino acids, and a CxxC, C/UxxT, or CxxS motif near the N-terminus end with a UXX-COOH motif. That final motif typically is missed during coding region feature prediction by genome annotation pipelines. This HMM covers proteins from several distinctive families with this feature. The seed alignment illustrates the final selenocysteine or aligned Cys or Ser residues, but the HMM also hits proteins that lack an equivalent motif at the C-terminus. This C-terminal selenocysteine-containing motif has not yet been described in the literature.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPlsiDEIKQILRMT 49
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDP---EALEEMLRLT 45

Arsenate Reductase (ArsC) family, Spx subfamily; Spx is a unique RNA polymerase (RNAP)-binding protein present in bacilli and some mollicutes. It inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP, disrupting complex formation between RNAP and certain transcriptional activator proteins like ResD and ComA. In response to oxidative stress, Spx can also activate transcription, making it a general regulator that exerts both positive and negative control over transcription initiation. Spx has been shown to exert redox-sensitive transcriptional control over genes like trxA (TRX) and trxB (TRX reductase), genes that function in thiol homeostasis. This redox-sensitive activity is dependent on the presence of a CXXC motif, present in some members of the Spx subfamily, that acts as a thiol/disulfide switch. Spx has also been shown to repress genes in a sulfate-dependent manner independent of the presence of the CXXC motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNVNVESMPLQDLY 80
Cdd:cd03032     1 MIKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKEELKEILSLTENGVEDIISTRSKAFKNLNIDIDELSLSELI 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1150403695  81 RLINEHPGLLRRPIIIDEKRLQVGYNEDEIRRFLP 115
Cdd:cd03032    81 RLISEHPSLLRRPIIIDEKRLQIGYNEDEIRQFLP 115

ArsC family; This family is related to glutaredoxins pfam00462.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   5 YTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNVNVESMPLQDLYRLIN 84
Cdd:pfam03960   1 YGSPNCSTCRKALAWLEEHGIEYQEIDYLETPPSKEELKDILAKLGDGVEALLNTRGTTYRELNLDKEDLSEDELLELIL 80

                          90       100
                  ....*....|....*....|....*....
gi 1150403695  85 EHPGLLRRPIIIDEKRLQVGYNEDEIRRF 113
Cdd:pfam03960  81 EHPSLIRRPIVVDGGKLLVGFNEEEIRAF 109

Arsenate reductase or related protein, glutaredoxin family [Inorganic ion transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNVNVESMPLQDLY 80
Cdd:COG1393     1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTPPTAEELKELLAKLGLGVEELLNTRGTTYRELGLKDKALSEEEAL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1150403695  81 RLINEHPGLLRRPIIIDEKRLQVGYNEDEIRRFLP 115
Cdd:COG1393    81 ALMLEHPSLIKRPIVVTGDKALVGFPPEEVLALLG 115

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILRMTEDGTDEIISTRSKVFQKLNV--NVESMPLQDL 79
Cdd:TIGR01617   1 IKVYGSPNCTTCKKARRWLEANGIEYQFIDIGEDGPTREELLDILSLLEDGIDPLLNTRGQSYRALNTsnTFLDLSDKEA 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1150403695  80 YRLINEHPGLLRRPIIIDEK-RLQVGYNEDEIRRFLP 115
Cdd:TIGR01617  81 LELLAEDPALLRRPLIVDTKnRLLIGFKSESIEEFKL 117

Arsenate Reductase (ArsC) family, Yffb subfamily; Yffb is an uncharacterized bacterial protein encoded by the yffb gene, related to the thioredoxin-fold arsenic reductases, ArsC. The structure of Yffb and the conservation of the catalytic cysteine suggest that it is likely to function as a glutathione (GSH)-dependent thiol reductase. ArsC catalyzes the reduction of arsenate [As(V)] to arsenite [As(III)], using reducing equivalents derived from GSH via glutaredoxin, through a single catalytic cysteine.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQILrmTEDGTDEIISTRSKVFQKLNVNVESMPLQD-LY 80
Cdd:cd03035     1 ITLYGIKNCDTVKKARKWLEARGVAYTFHDYRKDGLDAATLERWL--AKVGWETLLNKRGTTWRKLDDAQKAALDAAkAI 78

                          90       100
                  ....*....|....*....|....*..
gi 1150403695  81 RLINEHPGLLRRPIIIDEKRLQVGYNE 107
Cdd:cd03035    79 ALMLEHPSLIKRPVLETGGKVLVGFSE 105

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQI 45
Cdd:COG0695     1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRER 45

arsenate reductase (glutaredoxin); This model describes a distinct clade, including ArsC itself, of the broader ArsC family described by Pfam pfam03960. This clade is almost completely restricted to the Proteobacteria. An anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773. When expressed in Escherichia coli this ATP-driven oxyanion pump catalyses extrusion of the oxyanions arsenite, antimonite and arsenate. The pump is composed of two polypeptides, the products of the arsA and arsB genes. The pump alone produces resistance to arsenite and antimonite. This protein, ArsC, catalyzes the reduction of arsenate to arsenite, and thus extends resistance to include arsenate. [Cellular processes, Detoxification]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEI-PFVERNIfSEPLSIDEIKQIL-RMTEDGTDEIISTRSKVFQKLNVNVESMPLQDL 79
Cdd:TIGR00014   1 VTIYHNPRCSKSRNTLALLEDKGIePEVVKYL-KNPPTKSELEAIFaKLGLTVAREMIRTKEALYKELGLSDPNLSDQEL 79

                          90       100
                  ....*....|....*....|....*
gi 1150403695  80 YRLINEHPGLLRRPIIIDEKRLQVG 104
Cdd:TIGR00014  80 LDAMVAHPILLERPIVVAGDGARIG 104

Glutaredoxin-like protein, YruB-family; This glutaredoxin-like protein family contains the conserved CxxC motif and includes the Clostridium pasteurianum protein YruB which has been cloned from a rubredoxin operon. Somewhat related to NrdH, it is unknown whether this protein actually interacts with glutathione/glutathione reducatase, or, like NrdH, some other reductant system.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNI 32
Cdd:TIGR02196   1 KVKVYTTPWCPPCVKAKEYLTSKGVAFEEIDV 32

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQI 45
Cdd:cd02066     2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKEL 45

Glutaredoxin (GRX) family, Dishevelled, Egl-10, and Pleckstrin (DEP) subfamily; composed of uncharacterized proteins containing a GRX domain and additional domains DEP and DUF547, both of which have unknown functions. GRX is a glutathione (GSH) dependent reductase containing a redox active CXXC motif in a TRX fold. It has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. By altering the redox state of target proteins, GRX is involved in many cellular functions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNIFSEPLSIDEIKQI 45
Cdd:cd03027     3 VTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEER 46

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
                  ....*....|....*....|....*....|.
gi 1150403695   2 VTLYTSPSCTSCRKARAWLEEHEIPFVERNI 32
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPV 31

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

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1150403695   1 MVTLYTSPSCTSCRKARAWLEEHEIPFVERNI 32
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPV 32