2FC0,2E6L


Conserved Protein Domain Family
WRN_exo

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cd06141: WRN_exo 
Click on image for an interactive view with Cn3D
DEDDy 3'-5' exonuclease domain of WRN and similar proteins
WRN is a unique RecQ DNA helicase exhibiting an exonuclease activity. It contains a DEDDy-type DnaQ-like 3'-5' exonuclease domain possessing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific YX(3)D pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. Mutations in the WRN gene cause Werner syndrome, an autosomal recessive disorder associated with premature aging and increased susceptibility to cancer and type II diabetes. WRN interacts with key proteins involved in DNA replication, recombination, and repair. It is believed to maintain genomic stability and life span by participating in DNA processes. WRN is stimulated by Ku70/80, an important regulator of genomic stability.
Statistics
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PSSM-Id: 176653
View PSSM: cd06141
Aligned: 93 rows
Threshold Bit Score: 110.746
Threshold Setting Gi: 159486097
Created: 26-Mar-2008
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic site [active site]
Evidence:
  • Comment:The catalytic site is characterized by the presence of four negatively charged residues (DEDD) that serve as ligands for the two metal ions required for activity.
  • Comment:DEDDy exonucleases contain a conserved tyrosine at the ExoIII motif which is important in catalysis.
  • Structure:2FC0_A; Human WRN exonuclease binds two Mn ions in the catalytic site.
    View structure with Cn3D
  • Citation:PMID 9396823

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                     # #                                                
2FC0_A        29 SDCSFLSEDISMSls-------dGDVVGFDMEWPplynr----gklgkVALIQLCvSESKCYLFHVssm--svFPQGLKM 95  human
NP_001042816  22 TSDVAAADEWARGvraaa-rggrGLIVGLDCEWKpnhvs----wktskVAVLQLCaGERFCLVLQLfya--nrVPPAVAD 94  Japanese rice
EAZ12975     170 TSSHSLAAQFINEiare--rpqgGLIVGIDTEWRtdhlpn--gktcykVAVLQLC-VGRRCLLFQIyqa-gnmVPHELAE 243 Japanese rice
CAH66248      30 TKSGGKVESWLGEtyrihrscghPLVVGLDVEWRpaap------vpgpVAVLQLC-VDRRCLVFQIlha--dyLPDALSR 100 Indian rice
NP_001043775  25 TSSGAAVEGWLREvraa---ygpGLIVGLDVEWRpsygp-----aqnpVALLQLC-VDRRCLIFQLlya--dyVPGSLRR 93  Japanese rice
CAN64722      42 TDKAAIVDEWVQEilsi--yagkPMVVGLDIEWRpnrip----smsnkSATLQLC-INNKCLILQLfym--deIPQSLKG 112 wine grape
XP_001626062  67 TKCPNDADLWIHKnin-----ssTLAIGMDIEWRpqfipkklggkenkTATLQLA-VNHSCLVLHLfhmrldlLPRSLLN 140 starlet sea ane...
ABK26855      31 TDDGHVVENWVNQqt-------gQEIVGFDMEWRpsfqr----gwendTALLQLC-TDNGCLIIQMlfl--dfIPEALVS 96  Sitka spruce
XP_001771253  19 TKEGAVAQAWLKRq--------iGKVFGLDAEWRpsfrk----gvehkIALLQIC-GEDDCLIVQMlyl--dsIPTELVN 83  Physcomitrella ...
XP_001752549 231 TRQQCKVEKWLEVrk-------eEVKWGLDIEWRptfqk----gdyhnAALLQLS-LEECCLLVQLrfi--dmLPASLKS 296 Physcomitrella ...
Feature 1                        #                                                               
2FC0_A        96 LLENkaVKKAGVGIEGDQWKLLRDFDiklKNFVELTDVANKKlkct---etwSLNSLVKHLLGkqllkdksiRCSNWSKF 172 human
NP_001042816  95 LLGDpsVRLVGIGVGEDAAKLEADYGvwcAAPVDLEDACNRRlglvgtgrrlGLKGYAREVLGmamekprrvTMSNWEKR 174 Japanese rice
EAZ12975     244 FLADpsVRFVGVAVNNDMQRLANDCNlrvACAVDLRYAAAAVlgqpe-laraGLKRLALTVMGahmekekniTKSRWGEP 322 Japanese rice
CAH66248     101 FLADprYTFVGVGVRDDAARLRVGYGlevPRAVDLRALAADTlgrpd-lrraGLRALVREVMGvqmdkphhvRVSAWDKR 179 Indian rice
NP_001043775  94 FLAGaaDCFVGVGVDKDAERLSDDHGltvANTADLRPLAAQRlgrpe-lsqaGLQAVVRAVMGadlvkpqrvTMSRWDAS 172 Japanese rice
CAN64722     113 FLLDsnFTFVGVEVGADIDKLKNEYGlecSCSADVRILAMQRwpgr--frrpGLKDLAWEVVNlrmkkpkhvCMSNWEAR 190 wine grape
XP_001626062 141 VLGNirILKVGSGISGDAVKLLRDTEilcNGRSDTQVYAKVLalnq---dgtGLKKLAKTILGieldkpkyiSLSNWELF 217 starlet sea ane...
ABK26855      97 FLKDpgVKLVGVGIERDAAKLMNDHGlecGGQVELGALAAEKlerre-lkqaGLKGLAKEVLGlrlskpksiSMSNWAWA 175 Sitka spruce
XP_001771253  84 FLKDpsIKFPGVGIKGDALKLKRDWGlecNGAIDLTTLAASVlgrpe-lkaaGLKSLAKVVMDydmakpkrvTMSNWAKP 162 Physcomitrella ...
XP_001752549 297 LLANpnIKMGGVGILADTKKLKKDYGlicAGEVELTTLAVSTlknts-lkksGIATLTEKVLGvpyeknkrvTMSNWENR 375 Physcomitrella ...
Feature 1                #   #             
2FC0_A       173 pLTEDQKLYAATDAYAGFIIYRNLEI 198 human
NP_001042816 175 eLDPAQVEYACIDAYVSYKLGERVLA 200 Japanese rice
EAZ12975     323 tLTWEQVNYACIDAYVSYEIGRRLLS 348 Japanese rice
CAH66248     180 nLSEDQFKYACTDAFASREVGRRLYT 205 Indian rice
NP_001043775 173 cLSNEQIRYACIDAYVSFEVGRRLLR 198 Japanese rice
CAN64722     191 vLNENQVDYACIDAYASYRIGHKLII 216 wine grape
XP_001626062 218 pLTYEQASYAALDAWVSFKLFVELKQ 243 starlet sea anemone
ABK26855     176 iLQHRQIQYACIDAFVSLAIGKKLME 201 Sitka spruce
XP_001771253 163 iLDKVQVEYASLDAWVSYAIHQKLFQ 188 Physcomitrella patens subsp. patens
XP_001752549 376 dLTYAQIHYAAADAWLSYSIMMALLN 401 Physcomitrella patens subsp. patens

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