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Conserved domains on  [gi|404434375|ref|NP_009179|]
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three-prime repair exonuclease 1 isoform c [Homo sapiens]

Protein Classification

3'-5' exonuclease family protein( domain architecture ID 1085)

3'-5' exonuclease family protein may cleave nucleotides one at a time from the end (exo) of a polynucleotide chain

CATH:  3.30.420.10
Gene Ontology:  GO:0003676
PubMed:  11988770|11222749
SCOP:  4000547

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
DnaQ_like_exo super family cl10012
DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease ...
 4-201 3.98e-63

DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease superfamily is a structurally conserved group of 3'-5' exonucleases, which catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. It is also called the DEDD superfamily, after the four invariant acidic residues present in the catalytic site of its members. The superfamily consists of DNA- and RNA-processing enzymes such as the proofreading domains of DNA polymerases, other DNA exonucleases, RNase D, RNase T, Oligoribonuclease and RNA exonucleases (REX). The DnaQ-like exonuclease domain contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, which are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. The conservation patterns of the three motifs may vary among different subfamilies. DnaQ-like exonucleases are classified as DEDDy or DEDDh exonucleases depending on the variation of motif III as YX(3)D or HX(4)D, respectively. The significance of the motif differences is still unclear. Almost all RNase families in this superfamily are present only in eukaryotes and bacteria, but not in archaea, suggesting a later origin, which in some cases are accompanied by horizontal gene transfer.


The actual alignment was detected with superfamily member cd06136:

Pssm-ID: 447876 [Multi-domain]  Cd Length: 177  Bit Score: 197.17  E-value: 3.98e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   4 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 82
Cdd:cd06136    1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  83 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 162
Cdd:cd06136   75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 404434375 163 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 201
Cdd:cd06136  144 -----SLGSLYKRLFGQEPKNSHTAEGDVLALLKCALHK 177
 
Name Accession Description Interval E-value
TREX1_2 cd06136
DEDDh 3'-5' exonuclease domain of three prime repair exonuclease (TREX)1, TREX2, and similar ...
 4-201 3.98e-63

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.


Pssm-ID: 99839 [Multi-domain]  Cd Length: 177  Bit Score: 197.17  E-value: 3.98e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   4 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 82
Cdd:cd06136    1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  83 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 162
Cdd:cd06136   75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 404434375 163 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 201
Cdd:cd06136  144 -----SLGSLYKRLFGQEPKNSHTAEGDVLALLKCALHK 177
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 3-195 2.71e-09

exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other exonucleases;


Pssm-ID: 214685 [Multi-domain]  Cd Length: 169  Bit Score: 55.38  E-value: 2.71e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375     3 TLIFFDMEATGLPFSQPKVTELCLLAVHRCALEspptsqgppptvpppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 82
Cdd:smart00479   1 TLVVIDCETTGLDPGKDEIIEIAAVDVDGGEII-------------------EVFDTYVKPDRPITDYATEIHGITPEML 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375    83 AahGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGDRYDFPLLQAELAMLGLTSALDGaFCVDSItalkALERASSPSehg 162
Cdd:smart00479  62 D--DAPTFEEVLEELLEFLRGR-----ILVAGNSAHFDLRFLKLEHPRLGIKQPPKL-PVIDTL----KLARATNPG--- 126

                          170       180       190
                   ....*....|....*....|....*....|...
gi 404434375   163 pRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALL 195
Cdd:smart00479 127 -LPKYSLKKLAKRLLLEVIQRAHRALDDARATA 158
DnaQ COG0847
DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination ...
 4-194 1.93e-08

DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination and repair];


Pssm-ID: 440608 [Multi-domain]  Cd Length: 163  Bit Score: 52.87  E-value: 1.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   4 LIFFDMEATGLPFSQPKVTELCLLAVHrcalespptsQGppptvppppRVVDKLSLCVAPGKACSPAASEITGLSTAVLA 83
Cdd:COG0847    2 FVVLDTETTGLDPAKDRIIEIGAVKVD----------DG---------RIVETFHTLVNPERPIPPEATAIHGITDEDVA 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  84 AHGRqcFDDNLANLLLAFLRRQpqpwcLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVdsitalKALERASSPSEhgp 163
Cdd:COG0847   63 DAPP--FAEVLPELLEFLGGAV-----LVAHNA-AFDLGFLNAELRRAGLPLPPFPVLDT------LRLARRLLPGL--- 125

                        170       180       190
                 ....*....|....*....|....*....|.
gi 404434375 164 rKSYSLGSIYTRlYGQSPPDSHTAEGDVLAL 194
Cdd:COG0847  126 -PSYSLDALCER-LGIPFDERHRALADAEAT 154
 
Name Accession Description Interval E-value
TREX1_2 cd06136
DEDDh 3'-5' exonuclease domain of three prime repair exonuclease (TREX)1, TREX2, and similar ...
 4-201 3.98e-63

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.


Pssm-ID: 99839 [Multi-domain]  Cd Length: 177  Bit Score: 197.17  E-value: 3.98e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   4 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 82
Cdd:cd06136    1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  83 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 162
Cdd:cd06136   75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 404434375 163 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 201
Cdd:cd06136  144 -----SLGSLYKRLFGQEPKNSHTAEGDVLALLKCALHK 177
DEDDh cd06127
DEDDh 3'-5' exonuclease domain family; DEDDh exonucleases, part of the DnaQ-like (or DEDD) ...
 5-197 1.04e-13

DEDDh 3'-5' exonuclease domain family; DEDDh exonucleases, part of the DnaQ-like (or DEDD) exonuclease superfamily, catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. These proteins contain four invariant acidic residues in three conserved sequence motifs termed ExoI, ExoII and ExoIII. DEDDh exonucleases are classified as such because of the presence of specific Hx(4)D conserved pattern at the ExoIII motif. The four conserved acidic residues are clustered around the active site and serve as ligands for the two metal ions required for catalysis. Most DEDDh exonucleases are the proofreading subunits (epsilon) or domains of bacterial DNA polymerase III, the main replicating enzyme in bacteria, which functions as the chromosomal replicase. Other members include other DNA and RNA exonucleases such as RNase T, Oligoribonuclease, and RNA exonuclease (REX), among others.


Pssm-ID: 176648 [Multi-domain]  Cd Length: 159  Bit Score: 67.71  E-value: 1.04e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   5 IFFDMEATGLPFSQPKVTELCLLAVHrcalespptsqgppptvpPPPRVVDKLSLCVAPGKACSPAASEITGLSTAVLAa 84
Cdd:cd06127    1 VVFDTETTGLDPKKDRIIEIGAVKVD------------------GGIEIVERFETLVNPGRPIPPEATAIHGITDEMLA- 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  85 hGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGdRYDFPLLQAELAMLGLTsaLDGAFCVDSITALKALERAsspsehgpR 164
Cdd:cd06127   62 -DAPPFEEVLPEFLEFLGGR-----VLVAHNA-SFDLRFLNRELRRLGGP--PLPNPWIDTLRLARRLLPG--------L 124

                        170       180       190
                 ....*....|....*....|....*....|...
gi 404434375 165 KSYSLGSIYTRLYGQSPPDSHTAEGDVLALLSI 197
Cdd:cd06127  125 RSHRLGLLLAERYGIPLEGAHRALADALATAEL 157
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 3-195 2.71e-09

exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other exonucleases;


Pssm-ID: 214685 [Multi-domain]  Cd Length: 169  Bit Score: 55.38  E-value: 2.71e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375     3 TLIFFDMEATGLPFSQPKVTELCLLAVHRCALEspptsqgppptvpppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 82
Cdd:smart00479   1 TLVVIDCETTGLDPGKDEIIEIAAVDVDGGEII-------------------EVFDTYVKPDRPITDYATEIHGITPEML 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375    83 AahGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGDRYDFPLLQAELAMLGLTSALDGaFCVDSItalkALERASSPSehg 162
Cdd:smart00479  62 D--DAPTFEEVLEELLEFLRGR-----ILVAGNSAHFDLRFLKLEHPRLGIKQPPKL-PVIDTL----KLARATNPG--- 126

                          170       180       190
                   ....*....|....*....|....*....|...
gi 404434375   163 pRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALL 195
Cdd:smart00479 127 -LPKYSLKKLAKRLLLEVIQRAHRALDDARATA 158
DnaQ COG0847
DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination ...
 4-194 1.93e-08

DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination and repair];


Pssm-ID: 440608 [Multi-domain]  Cd Length: 163  Bit Score: 52.87  E-value: 1.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   4 LIFFDMEATGLPFSQPKVTELCLLAVHrcalespptsQGppptvppppRVVDKLSLCVAPGKACSPAASEITGLSTAVLA 83
Cdd:COG0847    2 FVVLDTETTGLDPAKDRIIEIGAVKVD----------DG---------RIVETFHTLVNPERPIPPEATAIHGITDEDVA 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  84 AHGRqcFDDNLANLLLAFLRRQpqpwcLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVdsitalKALERASSPSEhgp 163
Cdd:COG0847   63 DAPP--FAEVLPELLEFLGGAV-----LVAHNA-AFDLGFLNAELRRAGLPLPPFPVLDT------LRLARRLLPGL--- 125

                        170       180       190
                 ....*....|....*....|....*....|.
gi 404434375 164 rKSYSLGSIYTRlYGQSPPDSHTAEGDVLAL 194
Cdd:COG0847  126 -PSYSLDALCER-LGIPFDERHRALADAEAT 154
DnaQ_like_exo cd06125
DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease ...
 5-148 6.69e-07

DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease superfamily is a structurally conserved group of 3'-5' exonucleases, which catalyze the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. It is also called the DEDD superfamily, after the four invariant acidic residues present in the catalytic site of its members. The superfamily consists of DNA- and RNA-processing enzymes such as the proofreading domains of DNA polymerases, other DNA exonucleases, RNase D, RNase T, Oligoribonuclease and RNA exonucleases (REX). The DnaQ-like exonuclease domain contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, which are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. The conservation patterns of the three motifs may vary among different subfamilies. DnaQ-like exonucleases are classified as DEDDy or DEDDh exonucleases depending on the variation of motif III as YX(3)D or HX(4)D, respectively. The significance of the motif differences is still unclear. Almost all RNase families in this superfamily are present only in eukaryotes and bacteria, but not in archaea, suggesting a later origin, which in some cases are accompanied by horizontal gene transfer.


Pssm-ID: 176647 [Multi-domain]  Cd Length: 96  Bit Score: 46.66  E-value: 6.69e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   5 IFFDMEATGLPFSQPKVTELCLLAVHrcalespptsqgppptvpppprVVDKLSLCVAPGkacspaaseitglstavlaa 84
Cdd:cd06125    1 IAIDTEATGLDGAVHEIIEIALADVN----------------------PEDTAVIDLKDI-------------------- 38

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 404434375  85 hgrqcfddnlanlllaflRRQPQPWCLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVDSITA 148
Cdd:cd06125   39 ------------------LRDKPLAILVGHNG-SFDLPFLNNRCAELGLKYPLLAGSWIDTIKL 83
PolC COG2176
DNA polymerase III, alpha subunit (gram-positive type) [Replication, recombination and repair]; ...
 1-193 1.39e-04

DNA polymerase III, alpha subunit (gram-positive type) [Replication, recombination and repair];


Pssm-ID: 441779 [Multi-domain]  Cd Length: 181  Bit Score: 41.67  E-value: 1.39e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375   1 MQTLIFFDMEATGLPFSQPKVTELCLLAVHRCALespptsqgppptvpppprvVDKLSLCVAPGKACSPAASEITGLSTA 80
Cdd:COG2176    7 DLTYVVFDLETTGLSPKKDEIIEIGAVKVENGEI-------------------VDRFSTLVNPGRPIPPFITELTGITDE 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 404434375  81 VLAahgrqcfddnlanlllaflrRQPQP-------------WCLVAHNGdRYDFPLLQAELAMLGLtsALDGAFcVDSIT 147
Cdd:COG2176   68 MVA--------------------DAPPFeevlpefleflgdAVLVAHNA-SFDLGFLNAALKRLGL--PFDNPV-LDTLE 123

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 404434375 148 ALKALerasspseHGPRKSYSLGSIyTRLYGQSPPDSHTAEGDVLA 193
Cdd:COG2176  124 LARRL--------LPELKSYKLDTL-AERLGIPLEDRHRALGDAEA 160
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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