Conserved Protein Domain Family
TREX1_2

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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
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PSSM-Id: 99839
View PSSM: cd06136
Aligned: 12 rows
Threshold Bit Score: 211.808
Threshold Setting Gi: 19920610
Created: 3-Jan-2008
Updated: 17-Jan-2013
Structure
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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
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            ####  #                                                                     
2O4G_A        16 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 82
2OA8_A        11 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 77
2O4I_A        16 LIFLDLEATGLp---sSRPEVTELCLLAVHRRALENTsisqgh----------pppvprPPRVVDKLSLCIAPGKACSPG 82
1Y97_A        12 FVFLDLEATGLp---sVEPEIAELSLFAVHRSSLENPehdes-------------galvLPRVLDKLTLCXCPERPFTAK 75
gi 115661024  12 FVFLDFETSHLip--rDRPKIIELSLIAVNRTGLLNSdvhtalncarkenftfdlskvtLPRIIDKLTLCVDPRKDTSPQ 89
gi 19920610   20 FAVLDLETTNLpayrnNRVSITELCIYAFEAALLKKKkkeqdqd--------eqqelpaAPRVLHKLNVLFQPSMVVDPE 91
gi 91079955    7 FVFFDLETTGLpkfeeNRTRITEFCAVAVRADHIGLQtaq----------------kckLPRVQSKLSLCFNPARAICPQ 70
gi 156550374  15 FVFFDLETSDLik-ghRMPRITELSMVATDRNSLKNDmrd----------------klaLPRIMHKLTIPICPNAPIHQE 77
gi 156376678   2 FIFLDLETTGLr----RPIEITEICLIAVQKDHLLRAaet-----------------ktEPRLIDKLSICVKPVQNIECG 60
gi 157103173   8 FVFFDLETTDLig--iKTPKITEISLIACSRKHLLDTkr------------------geLPRVLHKQTFCLNPQRMIHPR 67
gi 91079959   34 FVFLDLETTGLphlehNKTRITELCAVSVRADHIELGc---------------------FPRVQNKLSLCFNPMKMISPE 92
gi 158296273   7 FVFFDLETTGLpeyehFRTKITELSMVACAREHLLEAst-------------------ePPRVTHKLSLCFNPHRMITLG 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #   #                                      ##  ###                              
2O4G_A        83 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 162
2OA8_A        78 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 157
2O4I_A        83 ASEITGLSKAELEvqgrQRFDDNLAILLRAFLQRQPQPCCLVAHNGDRYDFPLLQTELARLSTPSPlDGTFCVDSIAALK 162
1Y97_A        76 ASEITGLSSEGLArcrkAGFDGAVVRTLQAFLSRQAGPICLVAHNGFDYDFPLLCAELRRLGARLP-RDTVCLDTLPALR 154
gi 115661024  90 SAELTKLDKHNLDknkkLPFDEDVIAMLNIFLSRQEAPVCLVAHNGMRFDFAILRSELSQLTTGDPlADLYCVDSLSGFR 169
gi 19920610   92 AERITGLSNYLLEr--eSQLDTDAAQLIVSFLKHLPSPVCLVAHNGWGFDFPILRQAFEKLNIELP-QSLTCVDSLRAFM 168
gi 91079955   71 ATKLTGLSNELLEh--qAHFSSQTLNVIKNWLDVNEKPICLVAHNGNEFDFPILRAEIENTGENLP-EDILCLDSIIAFK 147
gi 156550374  78 ASFASNLWNDSLEh--fKPFDKDTYNMIMLFINRLPGVICFVAHNGNRFDYPVFLSEIDKLQMTFP-DRILCVDTLIAFK 154
gi 156376678  61 ASSITGINKMDLAe--kREFDRKLAKVIKTFLRRQPSPSCLVAHSGDRFDFDILASEFVNAGVKFP-SEIQAADSWKAFR 137
gi 157103173  68 ASETTGLYNDLLEd--eSKFDENTAQLIVLFLRRLQAPTCLVAHNGNRFDFVILKKELESLNAQLP-DDTYCVDSLPLFQ 144
gi 91079959   93 ATSLTGLSNDLLEy--qASFSSDAVDVIRKWLEMNQKPICLVAHNGNRFDYPILRAEVEKTRNKLP-EDILCLDSLNAFR 169
gi 158296273  68 SSQATGLYNDLLEk--eAKFDANAGEMVKLFLERLQKPVCLVAHNGQRFDFILLKQHLLRIDVALP-GDLYCVDSLPAFR 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
2O4G_A       163 ALEQasspsgn--------------------------------------------------------------------- 173
2OA8_A       158 ALEQasspsgn--------------------------------------------------------------------- 168
2O4I_A       163 ALEQasspsgn--------------------------------------------------------------------- 173
1Y97_A       155 GLDRahshgtr--------------------------------------------------------------------- 165
gi 115661024 170 AGFTtekqgerkqregknkqestwmpspepdlslkrklpycdiyspgmafqysqkrvpdnfyhsvhggggllprldtdqs 249
gi 19920610  169 EIDDtqqketsqlkvpndvqeiipelkpkqntetclkepeavvnidwrtrnettpnrpilk------------------- 229
gi 91079955  148 EIDTleggavaskirpptlclsnylilqivkskidqacrvaeeftklyyetsdkrrhlmskly----------------- 210
gi 156550374 155 EFFSdaqpanmppipvvpigvdevdeeeleqlskqdpnaslddewndslcsvvdelekvrt------------------- 215
gi 156376678 138 KLHQaeelktseakrtt--------------------------------------------------------------- 154
gi 157103173 145 ALEQareqkakaaqenadneladlelcaltameelegspstlslmqkrnettpqrgkitenyk----------------- 207
gi 91079959  170 SIDTleaeavkqppkgeipfefndgydellsqavdeyekqmkltpe---------------------------------- 215
gi 158296273 145 EIEAdvdrsyfennegldseipeleyqalrvmeelerskdwlkerqkqnettpqsgrveqkykqalrdylav-------- 216
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
2O4G_A           --------------------------------------------------------------------------------
2OA8_A           --------------------------------------------------------------------------------
2O4I_A           --------------------------------------------------------------------------------
1Y97_A           --------------------------------------------------------------------------------
gi 115661024 250 agvkmssykssdvgsypssnvsgatihdsprtmprsyshasdnlltpypllspskqplnpytdqlkektpksrhhhssad 329
gi 19920610  230 -----------------------------------------------------------------pteafakrkllrdgd 244
gi 91079955  211 ---------------------------------------------------------------ldsgllawngngvngne 227
gi 156550374 216 -----------------------------------------------------------------kdsvrtslscgngkd 230
gi 156376678     --------------------------------------------------------------------------------
gi 157103173 208 --------------------------------------------------------------ralrsylditpsqdgtss 225
gi 91079959      --------------------------------------------------------------------------------
gi 158296273 217 ------------------------------------------------------spnerqsasppepsddsdesakapqr 242
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
Feature 1                                                  #               #    #           
2O4G_A       174 -----------------------------------gsrksySLGSIYTRLYWQAPTDSHTAEGDVLTLLSICQWK 213
2OA8_A       169 -----------------------------------gsrksySLGSIYTRLYWQAPTDSHTAEGDVLTLLSICQWK 208
2O4I_A       174 -----------------------------------gsrksySLGSIYTRLYWQAPTDSATAEGDVLTLLSICQWK 213
1Y97_A       166 ----------------------------------argrqgySLGSLFHRYFRAEPSAAHSAEGDVHTLLLIFLHR 206
gi 115661024 330 vtthevkwkvasppssppqlkkshsepchtkghskpqrisySLVNIFKRTFGTDPPHSHSAEGDVMSLIKVLLPR 404
gi 19920610  245 eddleeqtppkrkpdefrsrrqlfsgckcaenkrypprgvyNLESLYTRIFKIPALSAHQAEADVVMTTKLIQHY 319
gi 91079955  228 riqkffidlptsdhiintldaqpvldsavngqltfmiqvsgTVRYQDRVPKSFQQNFIITAQGDKWKIVSDCFRL 302
gi 156550374 231 vldaitnkkqqadgkssgsttpksspksmqavnektpenqiIKNSLYSHMIGCEAKNLHSAEGDCISMLTCVCQM 305
gi 156376678 155 ----------------------------rtklapytgrlsfSLGNLYKRMTGSEIENSHTAEGDTLALLQLALKK 201
gi 157103173 226 qrrspprskrqlfpddksvmdpssgadtpttssqksakkrfRLCDVHERLLGQAPKISHYAECDVKALLKCAIAE 300
gi 91079959  216 qvqkinettpqkqkicsttgnggpgastkrnfghirefvsyKLEDVYKRLTSKEPISAHEAEGDVTMLVTCAAVY 290
gi 158296273 243 ptksrkrlfddaltngtdkeedegvkplaapavwngpkkrfNLSELYRRTVGKELLKAHCAEADVLALMDCAIVH 317

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