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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411 157 GRITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGGLMALNSLRN 229
Cdd:cd03027   1 GRVTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLEE 73

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411 157 GRITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGGLMALNSLRN 229
Cdd:cd03027   1 GRVTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLEE 73

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18399411   284 LPIKDRLMKMKIVKNCFSGAEMVEILIDYLDC-GRKKAVEIGKRLAEKHFIHHVFGE-NEFEDGNHYYRF 351
Cdd:pfam00610   2 VKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIiTREEAVELGQLLLDQGLIHHVGDKhGLFKDSYYFYRF 71

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411 158 RITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGG 220
Cdd:COG0695   1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGG 63

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18399411  159 ITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGGLMALNSLRNSGEFD 234
Cdd:PRK10638   4 VEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLD 79

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411 157 GRITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGGLMALNSLRN 229
Cdd:cd03027   1 GRVTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLEE 73

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18399411   284 LPIKDRLMKMKIVKNCFSGAEMVEILIDYLDC-GRKKAVEIGKRLAEKHFIHHVFGE-NEFEDGNHYYRF 351
Cdd:pfam00610   2 VKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIiTREEAVELGQLLLDQGLIHHVGDKhGLFKDSYYFYRF 71

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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18399411 158 RITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGG---LMALN 225
Cdd:cd02066   1 KVVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGyddLKALH 71

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18399411   159 ITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHF 218
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in Epac-like proteins. Epac (exchange proteins directly activated by cAMP) proteins are GEFs (guanine-nucleotide-exchange factors) for the small GTPases, Rap1 and Rap2. They are directly regulated by cyclic AMP, a second messenger that plays a role in the control of diverse cellular processes, such as cell adhesion and insulin secretion. Epac-like proteins share a common domain architecture, containing RasGEF, DEP and CAP-effector (cAMP binding) domains. The DEP domain is involved in membrane localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18399411 278 RVLRQKL------PIKDRLMKMKIVKNCFSGAEMVEILID---YLDCgRKKAVEIGKRLAEKHFIHHVFGENEFEDGNHY 348
Cdd:cd04437   3 RALRNAIlsdaphLIRDRKYHLRTYRQCCVGTELVDWLLQqspCVQS-RSQAVGMWQVLLEEGVLLHVDQELHFQDKYQF 81

                        90
                ....*....|...
gi 18399411 349 YRFLEHEPFVSKC 361
Cdd:cd04437  82 YRFSDDECSPAPL 94

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        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411 158 RITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERTGSSQVPQIFFNEKHFGG 220
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLNGYRSVPVVVIGDEHLSG 63

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in DEPDC5-like proteins. DEPDC5, in human also known as KIAA0645, is a DEP domain containing protein of unknown function.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18399411 298 NCFSGAEMVEILIDYLD--CGRKKAVEIGKRLAEKHFIHHVFGENEFEDGNHYYRF 351
Cdd:cd04449  28 NCFIGSEAVSWLINNFEdvDTREEAVELGQELMNEGLIEHVSGRHPFLDGFYFYYI 83

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human 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 human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18399411 158 RITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSR---EKELVERTGSSQVPQIFFNEKHFGGLMALNSLRNSGE 232
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGseiQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGK 78

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in BBRC3-like proteins. BBRC3, also known as DEPDC1B, is a DEP containing protein of unknown function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18399411 277 VRVLRQKLPIKDRLMKMKIVKNCFSGAEMVEILIDYLDCG--------RKKAVEIGKRLAEKHFIHHV---FGENEFEDG 345
Cdd:cd04447   7 TELFRAGMPLRKHRQHFKSYENCFTASEAVDWLHELLRSNsnfgpevtRQQTVQLLKKFLKNHVIEDIkgrWGKEDLEDN 86

                ....*.
gi 18399411 346 NHYYRF 351
Cdd:cd04447  87 NHLYRF 92

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 2 found in DEP6-like proteins. DEP6 proteins contain two DEP and a PDZ domain. Their function is unknown.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 18399411 300 FSGAEMVEILIDYLDCG-RKKAVEIGKRLAEKHFIHHVFGENEFEDGNHYYRF 351
Cdd:cd04441  33 FVGSEFIDWLLQEGEAEsRREAVQLCRRLLEHGIIQHVSNKHHFFDSNLLYQF 85

glutaredoxin-like protein NrdH;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18399411  158 RITFFSRSNCRDSTAVRLFLRERGFDFSEINIDVYSSREKELVERtGSSQVPQIFFNEKHFGG 220
Cdd:PRK10329   2 RITIYTRNDCVQCHATKRAMESRGFDFEMINVDRVPEAAETLRAQ-GFRQLPVVIAGDLSWSG 63