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Conserved domains on  [gi|18375535|ref|NP_338599|]
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three-prime repair exonuclease 1 isoform b [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 ...
 14-211 3.14e-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: 197.94  E-value: 3.14e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  14 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 92
Cdd:cd06136   1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  93 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 172
Cdd:cd06136  75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18375535 173 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 211
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 ...
 14-211 3.14e-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: 197.94  E-value: 3.14e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  14 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 92
Cdd:cd06136   1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  93 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 172
Cdd:cd06136  75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18375535 173 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 211
Cdd:cd06136 144 -----SLGSLYKRLFGQEPKNSHTAEGDVLALLKCALHK 177
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 13-205 3.21e-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: 3.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535     13 TLIFFDMEATGLPFSQPKVTELCLLAVHRCALEspptsqgppptvpppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 92
Cdd:smart00479   1 TLVVIDCETTGLDPGKDEIIEIAAVDVDGGEII-------------------EVFDTYVKPDRPITDYATEIHGITPEML 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535     93 AahGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGDRYDFPLLQAELAMLGLTSALDGaFCVDSItalkALERASSPSehg 172
Cdd:smart00479  62 D--DAPTFEEVLEELLEFLRGR-----ILVAGNSAHFDLRFLKLEHPRLGIKQPPKL-PVIDTL----KLARATNPG--- 126

                          170       180       190
                   ....*....|....*....|....*....|...
gi 18375535    173 pRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALL 205
Cdd:smart00479 127 -LPKYSLKKLAKRLLLEVIQRAHRALDDARATA 158
DnaQ COG0847
DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination ...
 14-204 1.47e-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: 53.26  E-value: 1.47e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  14 LIFFDMEATGLPFSQPKVTELCLLAVHrcalespptsQGppptvppppRVVDKLSLCVAPGKACSPAASEITGLSTAVLA 93
Cdd:COG0847   2 FVVLDTETTGLDPAKDRIIEIGAVKVD----------DG---------RIVETFHTLVNPERPIPPEATAIHGITDEDVA 62

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  94 AHGRqcFDDNLANLLLAFLRRQpqpwcLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVdsitalKALERASSPSEhgp 173
Cdd:COG0847  63 DAPP--FAEVLPELLEFLGGAV-----LVAHNA-AFDLGFLNAELRRAGLPLPPFPVLDT------LRLARRLLPGL--- 125

                       170       180       190
                ....*....|....*....|....*....|.
gi 18375535 174 rKSYSLGSIYTRlYGQSPPDSHTAEGDVLAL 204
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 ...
 14-211 3.14e-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: 197.94  E-value: 3.14e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  14 LIFFDMEATGLPFS-QPKVTELCLLAVHRCALESPPTSQGPPPTVPppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 92
Cdd:cd06136   1 FVFLDLETTGLPKHnRPEITELCLVAVHRDHLLNTSRDKPALPRVL------DKLSLCFNPGRAISPGASEITGLSNDLL 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  93 AAhgRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSAlDGAFCVDSITALKALERasspsehg 172
Cdd:cd06136  75 EH--KAPFDSDTANLIKLFLRRQPKPICLVAHNGNRFDFPILRSELERLGTKLP-DDILCVDSLPAFRELDQ-------- 143

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18375535 173 prksySLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWR 211
Cdd:cd06136 144 -----SLGSLYKRLFGQEPKNSHTAEGDVLALLKCALHK 177
DEDDh cd06127
DEDDh 3'-5' exonuclease domain family; DEDDh exonucleases, part of the DnaQ-like (or DEDD) ...
 15-207 1.33e-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: 67.33  E-value: 1.33e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  15 IFFDMEATGLPFSQPKVTELCLLAVHrcalespptsqgppptvpPPPRVVDKLSLCVAPGKACSPAASEITGLSTAVLAa 94
Cdd:cd06127   1 VVFDTETTGLDPKKDRIIEIGAVKVD------------------GGIEIVERFETLVNPGRPIPPEATAIHGITDEMLA- 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  95 hGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGdRYDFPLLQAELAMLGLTsaLDGAFCVDSITALKALERAsspsehgpR 174
Cdd:cd06127  62 -DAPPFEEVLPEFLEFLGGR-----VLVAHNA-SFDLRFLNRELRRLGGP--PLPNPWIDTLRLARRLLPG--------L 124

                       170       180       190
                ....*....|....*....|....*....|...
gi 18375535 175 KSYSLGSIYTRLYGQSPPDSHTAEGDVLALLSI 207
Cdd:cd06127 125 RSHRLGLLLAERYGIPLEGAHRALADALATAEL 157
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 13-205 3.21e-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: 3.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535     13 TLIFFDMEATGLPFSQPKVTELCLLAVHRCALEspptsqgppptvpppprvvDKLSLCVAPGKACSPAASEITGLSTAVL 92
Cdd:smart00479   1 TLVVIDCETTGLDPGKDEIIEIAAVDVDGGEII-------------------EVFDTYVKPDRPITDYATEIHGITPEML 61

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535     93 AahGRQCFDDNLANLLLAFLRRqpqpwCLVAHNGDRYDFPLLQAELAMLGLTSALDGaFCVDSItalkALERASSPSehg 172
Cdd:smart00479  62 D--DAPTFEEVLEELLEFLRGR-----ILVAGNSAHFDLRFLKLEHPRLGIKQPPKL-PVIDTL----KLARATNPG--- 126

                          170       180       190
                   ....*....|....*....|....*....|...
gi 18375535    173 pRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALL 205
Cdd:smart00479 127 -LPKYSLKKLAKRLLLEVIQRAHRALDDARATA 158
DnaQ COG0847
DNA polymerase III, epsilon subunit or related 3'-5' exonuclease [Replication, recombination ...
 14-204 1.47e-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: 53.26  E-value: 1.47e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  14 LIFFDMEATGLPFSQPKVTELCLLAVHrcalespptsQGppptvppppRVVDKLSLCVAPGKACSPAASEITGLSTAVLA 93
Cdd:COG0847   2 FVVLDTETTGLDPAKDRIIEIGAVKVD----------DG---------RIVETFHTLVNPERPIPPEATAIHGITDEDVA 62

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  94 AHGRqcFDDNLANLLLAFLRRQpqpwcLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVdsitalKALERASSPSEhgp 173
Cdd:COG0847  63 DAPP--FAEVLPELLEFLGGAV-----LVAHNA-AFDLGFLNAELRRAGLPLPPFPVLDT------LRLARRLLPGL--- 125

                       170       180       190
                ....*....|....*....|....*....|.
gi 18375535 174 rKSYSLGSIYTRlYGQSPPDSHTAEGDVLAL 204
Cdd:COG0847 126 -PSYSLDALCER-LGIPFDERHRALADAEAT 154
DnaQ_like_exo cd06125
DnaQ-like (or DEDD) 3'-5' exonuclease domain superfamily; The DnaQ-like exonuclease ...
 15-158 6.91e-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: 6.91e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  15 IFFDMEATGLPFSQPKVTELCLLAVHrcalespptsqgppptvpppprVVDKLSLCVAPGkacspaaseitglstavlaa 94
Cdd:cd06125   1 IAIDTEATGLDGAVHEIIEIALADVN----------------------PEDTAVIDLKDI-------------------- 38

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18375535  95 hgrqcfddnlanlllaflRRQPQPWCLVAHNGdRYDFPLLQAELAMLGLTSALDGAFCVDSITA 158
Cdd:cd06125  39 ------------------LRDKPLAILVGHNG-SFDLPFLNNRCAELGLKYPLLAGSWIDTIKL 83
PolC COG2176
DNA polymerase III, alpha subunit (gram-positive type) [Replication, recombination and repair]; ...
 11-203 1.49e-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: 1.49e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  11 MQTLIFFDMEATGLPFSQPKVTELCLLAVHRCALespptsqgppptvpppprvVDKLSLCVAPGKACSPAASEITGLSTA 90
Cdd:COG2176   7 DLTYVVFDLETTGLSPKKDEIIEIGAVKVENGEI-------------------VDRFSTLVNPGRPIPPFITELTGITDE 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375535  91 VLAahgrqcfddnlanlllaflrRQPQP-------------WCLVAHNGdRYDFPLLQAELAMLGLtsALDGAFcVDSIT 157
Cdd:COG2176  68 MVA--------------------DAPPFeevlpefleflgdAVLVAHNA-SFDLGFLNAALKRLGL--PFDNPV-LDTLE 123

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 18375535 158 ALKALerasspseHGPRKSYSLGSIyTRLYGQSPPDSHTAEGDVLA 203
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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