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 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLY 80
Cdd:cd03032    1 MIKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKEELKEILSLTENGVEDIISTRSKAFKNLNIDIDELSLSELI 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446180148  81 SIIQDNPGLLRRPIILDNKRLQVGYNEDEIRRFLP 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 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLY 80
Cdd:COG1393    1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTPPTAEELKELLAKLGLGVEELLNTRGTTYRELGLKDKALSEEEAL 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446180148  81 SIIQDNPGLLRRPIILDNKRLQVGYNEDEIRRFLP 115
Cdd:COG1393   81 ALMLEHPSLIKRPIVVTGDKALVGFPPEEVLALLG 115

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 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLY 80
Cdd:cd03032    1 MIKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKEELKEILSLTENGVEDIISTRSKAFKNLNIDIDELSLSELI 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446180148  81 SIIQDNPGLLRRPIILDNKRLQVGYNEDEIRRFLP 115
Cdd:cd03032   81 RLISEHPSLLRRPIIIDEKRLQIGYNEDEIRQFLP 115

ArsC family; This family is related to glutaredoxins pfam00462.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446180148    5 FTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLYSIIQ 84
Cdd:pfam03960   1 YGSPNCSTCRKALAWLEEHGIEYQEIDYLETPPSKEELKDILAKLGDGVEALLNTRGTTYRELNLDKEDLSEDELLELIL 80

                          90       100
                  ....*....|....*....|....*....
gi 446180148   85 DNPGLLRRPIILDNKRLQVGYNEDEIRRF 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 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLY 80
Cdd:COG1393    1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTPPTAEELKELLAKLGLGVEELLNTRGTTYRELGLKDKALSEEEAL 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 446180148  81 SIIQDNPGLLRRPIILDNKRLQVGYNEDEIRRFLP 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 446180148    2 VTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNV--DIDSLPLQDL 79
Cdd:TIGR01617   1 IKVYGSPNCTTCKKARRWLEANGIEYQFIDIGEDGPTREELLDILSLLEDGIDPLLNTRGQSYRALNTsnTFLDLSDKEA 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 446180148   80 YSIIQDNPGLLRRPIILDNK-RLQVGYNEDEIRRFLP 115
Cdd:TIGR01617  81 LELLAEDPALLRRPLIVDTKnRLLIGFKSESIEEFKL 117

Arsenate Reductase (ArsC) family, ArsC subfamily; arsenic reductases similar to that encoded by arsC on the R733 plasmid of Escherichia coli. E. coli ArsC catalyzes the reduction of arsenate [As(V)] to arsenite [As(III)], the first step in the detoxification of arsenic, using reducing equivalents derived from glutathione (GSH) via glutaredoxin (GRX). ArsC contains a single catalytic cysteine, within a thioredoxin fold, that forms a covalent thiolate-As(V) intermediate, which is reduced by GRX through a mixed GSH-arsenate intermediate. This family of predominantly bacterial enzymes is unrelated to two other families of arsenate reductases which show similarity to low-molecular-weight acid phosphatases and phosphotyrosyl phosphatases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446180148   2 VTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQILKMTEDGTDEIISTRSKTYQKLNVDIDSLPLQDLYS 81
Cdd:cd03034    1 ITIYHNPRCSKSRNALALLEEAGIEPEIVEYLKTPPTAAELRELLAKLGISPRDLLRTKEAPYKELGLADPELSDEELID 80

                         90       100
                 ....*....|....*....|...
gi 446180148  82 IIQDNPGLLRRPIILDNKRLQVG 104
Cdd:cd03034   81 AMAAHPILIERPIVVTGDGAVLG 103

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEHLTIDEIKQI 45
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRER 45

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                         10        20        30
                 ....*....|....*....|....*....|..
gi 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERNI 32
Cdd:cd02976    1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDV 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 446180148   2 VTLFTSPSCTSCRKAKAWLQEHDIPYTERNIFSEhltiDEIKQILK 47
Cdd:cd02066    2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILED----GELREELK 43

Glutaredoxin (GRX) family, GRX bacterial class 1 and 3 (b_1_3)-like subfamily; composed of bacterial GRXs, 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 E. coli GRX1 and GRX3, which are members of this subfamily.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 446180148   2 VTLFTSPSCTSCRKAKAWLQEHDIPYTERNI 32
Cdd:cd03418    2 VEIYTKPNCPYCVRAKALLDKKGVDYEEIDV 32

putative reductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446180148   1 MVTLFTSPSCTSCRKAKAWLQEHDIPYTERN-----IFSEHLT--IDEIkqilkmtedGTDEIISTRSKTYQKLNvdids 73
Cdd:PRK10853   1 MVTLYGIKNCDTIKKARRWLEAQGIDYRFHDyrvdgLDSELLQgfIDEL---------GWEALLNTRGTTWRKLD----- 66

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 446180148  74 lplQDLYSIIQD----------NPGLLRRP-IILDNKRLQVGYNEDEIRRF 113
Cdd:PRK10853  67 ---ETQRNAITDaasaaalmleQPAIIKRPlLCAPGKPMLLGFSESSYQQF 114