Protein of unknown function, DUF547; Family of uncharacterized proteins from C. elegans and A. thaliana.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501  501 HNEKLAFFLNLYNAMVIHGLIRFGRLEGVIDRKSFFSDFQYLVGGHPYSLIAIKNGILRGNrrpPYSFVKPFssSDKRLE 580
Cdd:pfam04784   1 REEKLAFWINLYNALTIHAILYPGIPPSPWKRRSLFDKAAYNIGGHKYSLDDIEHGILRGN---PSNLKKPF--GDPRRK 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 778698501  581 LAYGEVNPLIHFGLCNGTKSSPRVRFYTPQGVEAELRCAAREF 623
Cdd:pfam04784  76 YALEYPDPRIHFALNCGSKSCPPLRAYTAENLEEQLEEAAREF 118

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 340 ELLEIVKFLRQRLPIQDRLIKMKIVKNCFSGSEMVEALIHRLDC-GRRKAVEIGKQMTQKLFIHHVFG-ENEFEDGNHFY 417
Cdd:cd04371    1 DLVRIMLDSDSGVPIKDRKYHLKTYPNCFTGSELVDWLLDNLEAiTREEAVELGQALLKHGLIHHVSDdKHTFRDSYALY 80

                 .
gi 778698501 418 R 418
Cdd:cd04371   81 R 81

Protein of unknown function, DUF547; Family of uncharacterized proteins from C. elegans and A. thaliana.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501  501 HNEKLAFFLNLYNAMVIHGLIRFGRLEGVIDRKSFFSDFQYLVGGHPYSLIAIKNGILRGNrrpPYSFVKPFssSDKRLE 580
Cdd:pfam04784   1 REEKLAFWINLYNALTIHAILYPGIPPSPWKRRSLFDKAAYNIGGHKYSLDDIEHGILRGN---PSNLKKPF--GDPRRK 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 778698501  581 LAYGEVNPLIHFGLCNGTKSSPRVRFYTPQGVEAELRCAAREF 623
Cdd:pfam04784  76 YALEYPDPRIHFALNCGSKSCPPLRAYTAENLEEQLEEAAREF 118

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 340 ELLEIVKFLRQRLPIQDRLIKMKIVKNCFSGSEMVEALIHRLDC-GRRKAVEIGKQMTQKLFIHHVFG-ENEFEDGNHFY 417
Cdd:cd04371    1 DLVRIMLDSDSGVPIKDRKYHLKTYPNCFTGSELVDWLLDNLEAiTREEAVELGQALLKHGLIHHVSDdKHTFRDSYALY 80

                 .
gi 778698501 418 R 418
Cdd:cd04371   81 R 81

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 778698501 231 RISFFSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQREKELMKRTGSTLVPQIFFNDKLFGG 293
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGG 63

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501  232 ISFFSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQREKELMKRTGSTLVPQIFFNDKLF 291
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

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        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 778698501  231 RISFFSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQREKELMKRTGSTLVPQIFFNDKLFGG 293
Cdd:TIGR02196   1 KVKVYTTPWCPPCVKAKEYLTSKGVAFEEIDVEKDAAAREELLKVYGQRGVPVIVIGHKIVVG 63

Protein of unknown function, DUF547; Family of uncharacterized proteins from C. elegans and A. thaliana.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501  501 HNEKLAFFLNLYNAMVIHGLIRFGRLEGVIDRKSFFSDFQYLVGGHPYSLIAIKNGILRGNrrpPYSFVKPFssSDKRLE 580
Cdd:pfam04784   1 REEKLAFWINLYNALTIHAILYPGIPPSPWKRRSLFDKAAYNIGGHKYSLDDIEHGILRGN---PSNLKKPF--GDPRRK 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 778698501  581 LAYGEVNPLIHFGLCNGTKSSPRVRFYTPQGVEAELRCAAREF 623
Cdd:pfam04784  76 YALEYPDPRIHFALNCGSKSCPPLRAYTAENLEEQLEEAAREF 118

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 778698501 231 RISFFSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQREKELMKRTGSTLVPQIFFNDKLFGGLVALNSL 300
Cdd:cd02066    1 KVVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKAL 70

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 778698501  351 RLPIQDRLIKMKIVKNCFSGSEMVEALIHRLDC-GRRKAVEIGKQMTQKLFIHHVFGE-NEFEDGNHFYRF 419
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIiTREEAVELGQLLLDQGLIHHVGDKhGLFKDSYYFYRF 71

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 778698501   348 LRQRLPIQDRLIKMKIVKNCFSGSEMVEALIHRLDC-GRRKAVEIGKQMTQKLFIHHVFGENE--FEDGNHFYRF 419
Cdd:smart00049   1 PETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLEIiDREEAVHLGQLLLDEGLIHHVNGPNKhtFKDSKALYRF 75

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        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 232 ISFFSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQREKELMKRTGSTL-VPQIFFNDKLFGG---LVAL 297
Cdd:cd03418    2 VEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGGRRtVPQIFIGDVHIGGcddLYAL 71

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 341 LLEIVKFLRQ--RLPIQDRLIKMKIVKNCFSGSEMVEALIHRLD--CGRRKAVEIGKQMTQKLFIHHVFGENEFEDGNHF 416
Cdd:cd04449    1 LAEIAEAMRDpsGIGIFDRSWHKGLPSNCFIGSEAVSWLINNFEdvDTREEAVELGQELMNEGLIEHVSGRHPFLDGFYF 80

                 ...
gi 778698501 417 YRF 419
Cdd:cd04449   81 YYI 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 778698501 235 FSRSNCRDCKAVRSFFNEKGLRFVEINVDVFP---QREKELMKRTGSTLVPQIFFNDKLFGGLVALNSLRNSGE 305
Cdd:cd03419    5 FSKSYCPYCKRAKSLLKELGVKPAVVELDQHEdgsEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGK 78

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in DEP6-like proteins. DEP6 proteins contain two DEP and a PDZ domain. Their function is unknown.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 778698501 348 LRQRLP----IQDRLIKMKIVKNCFSGSEMVEALI-HRLDCGRRKAVEIGKQMTQKLFIHHVFGEN-EFEDGNHFYRF 419
Cdd:cd04442    5 LRLRLHeakvIKDRRHHLRTYPNCFVGKELIDWLIeHKEASDRETAIKIMQKLLDHSIIHHVCDEHkEFKDAKLFYRF 82

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in GPR155-like proteins. GRP155-like proteins, also known as PGR22, contain an N-terminal permease domain, a central transmembrane region and a C-terminal DEP domain. They are orphan receptors of the class B G protein-coupled receptors. Their function is unknown.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 778698501 354 IQDRLIKMKIVKNCFSGSEMVEALIHR-LDCGRRKAVEIGKQMTQKLFIHHVFGENEFEDGNHFYRF 419
Cdd:cd04443   17 VKDRRCGLRTYKGVFCGCDLVSWLIEVgLAQDRGEAVLYGRRLLQGGVLQHITNEHHFRDENLLYRF 83

DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF activity is stimulated by phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), a lipid second messenger, and by the G beta-gamma subunits of heterotrimeric G proteins. The DEP domains are not involved in mediating these stimuli, but may be of importance for basal and stimulated levels Rac-GEF activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 778698501 349 RQRLPIQDRLIKMKIVKNCFSGSEMVEAL-----IHRLDCGrrkaVEIGKQMTQKLFIHHVFGENEFEDGNHFYRF 419
Cdd:cd04439   10 KQGSLIKDRRRKLSTFPKCFLGNEFVSWLleigeISKPEEG----VNLGQALLENGIIHHVSDKHQFKNEQVLYRF 81

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) Rom2-like proteins. Rom2-like proteins share a common domain architecture, containing, beside the RhoGEF domain, a DEP, a PH (pleckstrin homology) and a CNH domain. Rom2, a yeast GEF for Rho1 and Rho2, is involved in mediating stress response via the Ras-cAMP pathway and also plays a role in mediating resistance to sphingolipid disturbances.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 341 LLEIVKFLRQRLPIQDRlIKMKIV-KNCFSGSEMVE---ALIHRLDcgRRKAVEIGKQMTQKLFIHHVFGENEFEDGNH- 415
Cdd:cd04435    2 LSRVALQLRDKIPLGDH-TKDGITyRNSFTGKDAVTtiqGIIRTSD--RNLALLLGRSLDAQKFFHDVTYDHRLRDSVDe 78

                 ....
gi 778698501 416 FYRF 419
Cdd:cd04435   79 VYRF 82

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGEF (GDP/GTP exchange factor) PIKfyve-like proteins. PIKfyve contains N-terminal Fyve finger and DEP domains, a central chaperonin-like domain and a C-terminal PIPK (phosphatidylinositol phosphate kinase) domain. PIKfyve-like proteins are important phosphatidylinositol (3)-monophosphate (PtdIns(3)P)-5-kinases, producing PtdIns(3,5)P2, which plays a major role in multivesicular body (MVB) sorting and control of retrograde traffic from the vacuole back to the endosome and/or Golgi. PIKfyve itself has been shown to be play a role in regulating early-endosome-to-trans-Golgi network (TGN) retrograde trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501 340 ELLEIVKFLRQRLPIQDRLIKMKIVKNCFSGSEMVEALIHRLDCGRR-KAVEIGKQMTQKLFIHHVFGENEFEDGNHFYR 418
Cdd:cd04448    1 DLWEKICRSSTGIEFQDHRYRLRTYTNCILGKELVNWLIRQGKAATRvQAIAIGQALLDAGWIECVSDDDLFRDEYALYK 80

Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to plants. Multiple isoforms are found in A. thaliana and O.sativa.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778698501  235 FSRSNCRDCKAVRSFFNEKGLRFVEINVDVFPQR---EKELMKRTGSTLVPQIFFNDKLFGGLVALNSLRNSGEFDRRIK 311
Cdd:TIGR02189  13 FSRSSCCMCHVVKRLLLTLGVNPAVHEIDKEPAGkdiENALSRLGCSPAVPAVFVGGKLVGGLENVMALHISGSLVPMLK 92