2O4G,2OA8,2O4I,1Y97


Conserved Protein Domain Family
TREX1_2

?
cd06136: TREX1_2 
Click on image for an interactive view with Cn3D
DEDDh 3'-5' exonuclease domain of three prime repair exonuclease (TREX)1, TREX2, and similar proteins
Three prime repair exonuclease (TREX)1 and TREX2 are closely related DEDDh-type DnaQ-like 3'-5' exonucleases. They contain three conserved sequence motifs known as ExoI, II, and III, with a specific Hx(4)D conserved pattern at ExoIII. These motifs contain four conserved acidic residues that participate in coordination of divalent metal ions required for catalysis. Both proteins play a role in the metabolism and clearance of DNA. TREX1 is the major 3'-5' exonuclease activity detected in mammalian cells. Mutations in the human TREX1 gene can cause Aicardi-Goutieres syndrome (AGS), which is characterized by perturbed innate immunity and presents itself as a severe neurological disease. TREX1 degrades ssDNA generated by aberrant replication intermediates to prevent checkpoint activation and autoimmune disease. There are distinct structural differences between TREX1 and TREX2 that point to different biological roles for these proteins. The main difference is the presence of about 70 amino acids at the C-terminus of TREX1. In addition, TREX1 has a nonrepetitive proline-rich region that is not present in the TREX2 protein. Furthermore, TREX2 contains a conserved DNA binding loop positioned adjacent to the active site that has a sequence distinct from the corresponding loop in TREX1. Truncations in the C-terminus of human TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy (RVCL), a neurovascular syndrome featuring a progressive loss of visual acuity combined with a variable neurological picture.
Statistics
?
PSSM-Id: 99839
View PSSM: cd06136
Aligned: 12 rows
Threshold Bit Score: 211.808
Threshold Setting Gi: 19920610
Created: 3-Jan-2008
Updated: 2-Oct-2020
Structure
?
Program:
Drawing:
Aligned Rows:
 
Conserved site includes 15 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:The active site includes the catalytic site (characterized by four invariant acidic residues, DEDD) and the substrate (ssDNA) binding site.
  • Structure:2OA8_A; Mus musculus TREX1 binds ssDNA and two Ca ions; defined at 3.5A contacts.
    View structure with Cn3D

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1            ####  #                                                                     
2O4G_A        16 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 82  house mouse
2OA8_A        11 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 77  house mouse
2O4I_A        16 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 82  house mouse
1Y97_A        12 FVFLDLEATGLp---sVEPEIAELSLFAVHRSSLENPehdes-------------galvLPRVLDKLTLCXCPERPFTAK 75  human
XP_001191081  12 FVFLDFETSHLip--rDRPKIIELSLIAVNRTGLLNSdvhtalncarkenftfdlskvtLPRIIDKLTLCVDPRKDTSPQ 89  purple urchin
NP_608732     20 FAVLDLETTNLpayrnNRVSITELCIYAFEAALLKKKkkeqdqd--------eqqelpaAPRVLHKLNVLFQPSMVVDPE 91  fruit fly
XP_969322      7 FVFFDLETTGLpkfeeNRTRITEFCAVAVRADHIGLQtaq----------------kckLPRVQSKLSLCFNPARAICPQ 70  red flour beetle
XP_001599410  15 FVFFDLETSDLik-ghRMPRITELSMVATDRNSLKNDmrd----------------klaLPRIMHKLTIPICPNAPIHQE 77  jewel wasp
XP_001630486   2 FIFLDLETTGLr----RPIEITEICLIAVQKDHLLRAaet-----------------ktEPRLIDKLSICVKPVQNIECG 60  starlet sea ane...
XP_001647854   8 FVFFDLETTDLig--iKTPKITEISLIACSRKHLLDTkr------------------geLPRVLHKQTFCLNPQRMIHPR 67  yellow fever mo...
XP_969470     34 FVFLDLETTGLphlehNKTRITELCAVSVRADHIELGc---------------------FPRVQNKLSLCFNPMKMISPE 92  red flour beetle
XP_557337      7 FVFFDLETTGLpeyehFRTKITELSMVACAREHLLEAst-------------------ePPRVTHKLSLCFNPHRMITLG 67  Anopheles gambi...
Feature 1        #   #                                      ##  ###                              
2O4G_A        83 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 162 house mouse
2OA8_A        78 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 157 house mouse
2O4I_A        83 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 162 house mouse
1Y97_A        76 ASEITGLSSEGLArcrkAGFDGAVVRTLQAFLSRQAGPICLVAHNGFDYDFPLLCAELRRLGARLP-RDTVCLDTLPALR 154 human
XP_001191081  90 SAELTKLDKHNLDknkkLPFDEDVIAMLNIFLSRQEAPVCLVAHNGMRFDFAILRSELSQLTTGDPlADLYCVDSLSGFR 169 purple urchin
NP_608732     92 AERITGLSNYLLEr--eSQLDTDAAQLIVSFLKHLPSPVCLVAHNGWGFDFPILRQAFEKLNIELP-QSLTCVDSLRAFM 168 fruit fly
XP_969322     71 ATKLTGLSNELLEh--qAHFSSQTLNVIKNWLDVNEKPICLVAHNGNEFDFPILRAEIENTGENLP-EDILCLDSIIAFK 147 red flour beetle
XP_001599410  78 ASFASNLWNDSLEh--fKPFDKDTYNMIMLFINRLPGVICFVAHNGNRFDYPVFLSEIDKLQMTFP-DRILCVDTLIAFK 154 jewel wasp
XP_001630486  61 ASSITGINKMDLAe--kREFDRKLAKVIKTFLRRQPSPSCLVAHSGDRFDFDILASEFVNAGVKFP-SEIQAADSWKAFR 137 starlet sea ane...
XP_001647854  68 ASETTGLYNDLLEd--eSKFDENTAQLIVLFLRRLQAPTCLVAHNGNRFDFVILKKELESLNAQLP-DDTYCVDSLPLFQ 144 yellow fever mo...
XP_969470     93 ATSLTGLSNDLLEy--qASFSSDAVDVIRKWLEMNQKPICLVAHNGNRFDYPILRAEVEKTRNKLP-EDILCLDSLNAFR 169 red flour beetle
XP_557337     68 SSQATGLYNDLLEk--eAKFDANAGEMVKLFLERLQKPVCLVAHNGQRFDFILLKQHLLRIDVALP-GDLYCVDSLPAFR 144 Anopheles gambi...
Feature 1                                                                                        
2O4G_A       163 ALEQasspsgn--------------------------------------------------------------------- 173 house mouse
2OA8_A       158 ALEQasspsgn--------------------------------------------------------------------- 168 house mouse
2O4I_A       163 ALEQasspsgn--------------------------------------------------------------------- 173 house mouse
1Y97_A       155 GLDRahshgtr--------------------------------------------------------------------- 165 human
XP_001191081 170 AGFTtekqgerkqregknkqestwmpspepdlslkrklpycdiyspgmafqysqkrvpdnfyhsvhggggllprldtdqs 249 purple urchin
NP_608732    169 EIDDtqqketsqlkvpndvqeiipelkpkqntetclkepeavvnidwrtrnettpnrpilk------------------- 229 fruit fly
XP_969322    148 EIDTleggavaskirpptlclsnylilqivkskidqacrvaeeftklyyetsdkrrhlmskly----------------- 210 red flour beetle
XP_001599410 155 EFFSdaqpanmppipvvpigvdevdeeeleqlskqdpnaslddewndslcsvvdelekvrt------------------- 215 jewel wasp
XP_001630486 138 KLHQaeelktseakrtt--------------------------------------------------------------- 154 starlet sea ane...
XP_001647854 145 ALEQareqkakaaqenadneladlelcaltameelegspstlslmqkrnettpqrgkitenyk----------------- 207 yellow fever mo...
XP_969470    170 SIDTleaeavkqppkgeipfefndgydellsqavdeyekqmkltpe---------------------------------- 215 red flour beetle
XP_557337    145 EIEAdvdrsyfennegldseipeleyqalrvmeelerskdwlkerqkqnettpqsgrveqkykqalrdylav-------- 216 Anopheles gambi...
Feature 1                                                                                        
2O4G_A           --------------------------------------------------------------------------------     house mouse
2OA8_A           --------------------------------------------------------------------------------     house mouse
2O4I_A           --------------------------------------------------------------------------------     house mouse
1Y97_A           --------------------------------------------------------------------------------     human
XP_001191081 250 agvkmssykssdvgsypssnvsgatihdsprtmprsyshasdnlltpypllspskqplnpytdqlkektpksrhhhssad 329 purple urchin
NP_608732    230 -----------------------------------------------------------------pteafakrkllrdgd 244 fruit fly
XP_969322    211 ---------------------------------------------------------------ldsgllawngngvngne 227 red flour beetle
XP_001599410 216 -----------------------------------------------------------------kdsvrtslscgngkd 230 jewel wasp
XP_001630486     --------------------------------------------------------------------------------     starlet sea ane...
XP_001647854 208 --------------------------------------------------------------ralrsylditpsqdgtss 225 yellow fever mo...
XP_969470        --------------------------------------------------------------------------------     red flour beetle
XP_557337    217 ------------------------------------------------------spnerqsasppepsddsdesakapqr 242 Anopheles gambi...
Feature 1                                                  #               #    #           
2O4G_A       174 -----------------------------------gsrksySLGSIYTRLYWQAPTDSHTAEGDVLTLLSICQWK 213 house mouse
2OA8_A       169 -----------------------------------gsrksySLGSIYTRLYWQAPTDSHTAEGDVLTLLSICQWK 208 house mouse
2O4I_A       174 -----------------------------------gsrksySLGSIYTRLYWQAPTDSATAEGDVLTLLSICQWK 213 house mouse
1Y97_A       166 ----------------------------------argrqgySLGSLFHRYFRAEPSAAHSAEGDVHTLLLIFLHR 206 human
XP_001191081 330 vtthevkwkvasppssppqlkkshsepchtkghskpqrisySLVNIFKRTFGTDPPHSHSAEGDVMSLIKVLLPR 404 purple urchin
NP_608732    245 eddleeqtppkrkpdefrsrrqlfsgckcaenkrypprgvyNLESLYTRIFKIPALSAHQAEADVVMTTKLIQHY 319 fruit fly
XP_969322    228 riqkffidlptsdhiintldaqpvldsavngqltfmiqvsgTVRYQDRVPKSFQQNFIITAQGDKWKIVSDCFRL 302 red flour beetle
XP_001599410 231 vldaitnkkqqadgkssgsttpksspksmqavnektpenqiIKNSLYSHMIGCEAKNLHSAEGDCISMLTCVCQM 305 jewel wasp
XP_001630486 155 ----------------------------rtklapytgrlsfSLGNLYKRMTGSEIENSHTAEGDTLALLQLALKK 201 starlet sea anemone
XP_001647854 226 qrrspprskrqlfpddksvmdpssgadtpttssqksakkrfRLCDVHERLLGQAPKISHYAECDVKALLKCAIAE 300 yellow fever mosquito
XP_969470    216 qvqkinettpqkqkicsttgnggpgastkrnfghirefvsyKLEDVYKRLTSKEPISAHEAEGDVTMLVTCAAVY 290 red flour beetle
XP_557337    243 ptksrkrlfddaltngtdkeedegvkplaapavwngpkkrfNLSELYRRTVGKELLKAHCAEADVLALMDCAIVH 317 Anopheles gambiae st...

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap