NCBI Conserved Domain Search

Conserved domains on [gi|530365443|ref|XP_005245575|]

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interferon-stimulated 20 kDa exonuclease-like 2 isoform X2 [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 ...

33-121

2.85e-56

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 cd06149:

Pssm-ID: 447876 Cd Length: 157 Bit Score: 172.62 E-value: 2.85e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  33 GEILKILTGKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLNRKADCPENATMSLKHLTKKLLNRDIQVGKSGHSSVED 112
Cdd:cd06149   69 KEILKILKGKVVVGHAIHNDFKALKYFHPKHMTRDTSTIPLLNRKAGFPENCRVSLKVLAKRLLHRDIQVGRQGHSSVED 148


                 ....*....
gi 530365443 113 AQATMELYK 121
Cdd:cd06149  149 ARATMELYK 157

Name

Accession

Description

Interval

E-value

ISG20

cd06149

DEDDh 3'-5' exonuclease domain of Interferon Stimulated Gene product of 20 kDa, and similar ...

33-121

2.85e-56

DEDDh 3'-5' exonuclease domain of Interferon Stimulated Gene product of 20 kDa, and similar proteins; Interferon (IFN) Stimulated Gene product of 20 kDa (ISG20) is an IFN-induced antiviral exonuclease with a strong preference for single-stranded RNA and minor activity towards single-stranded DNA. It was also independently identified by its response to estrogen and was called HEM45 (human estrogen regulated transcript). ISG20 is a DEDDh-type DnaQ-like 3'-5' exonuclease containing three conserved sequence motifs termed ExoI, ExoII and ExoIII with a specific Hx(4)D conserved 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. ISG20 may be a major effector of innate immunity against pathogens including viruses, bacteria, and parasites. It is located in promyelocytic leukemia (PML) nuclear bodies, sites for oncogenic DNA viral transcription and replication. It may carry out its function by degrading viral RNAs as part of the IFN-regulated antiviral response.

Pssm-ID: 99852 Cd Length: 157 Bit Score: 172.62 E-value: 2.85e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  33 GEILKILTGKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLNRKADCPENATMSLKHLTKKLLNRDIQVGKSGHSSVED 112
Cdd:cd06149   69 KEILKILKGKVVVGHAIHNDFKALKYFHPKHMTRDTSTIPLLNRKAGFPENCRVSLKVLAKRLLHRDIQVGRQGHSSVED 148


                 ....*....
gi 530365443 113 AQATMELYK 121
Cdd:cd06149  149 ARATMELYK 157

EXOIII

smart00479

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

34-128

4.38e-15

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

Pssm-ID: 214685 [Multi-domain] Cd Length: 169 Bit Score: 67.71 E-value: 4.38e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443    34 EILKILTGK-IVVGHAIHNDFKALQYFHPK--------SLTRDTSHIpplnRKADCPENATMSLKHLTKKLLNRDIQvgk 104
Cdd:smart00479  73 ELLEFLRGRiLVAGNSAHFDLRFLKLEHPRlgikqppkLPVIDTLKL----ARATNPGLPKYSLKKLAKRLLLEVIQ--- 145

                           90       100
                   ....*....|....*....|....
gi 530365443   105 SGHSSVEDAQATMELYKLVEVEWE 128
Cdd:smart00479 146 RAHRALDDARATAKLFKKLLERLE 169

Name

Accession

Description

Interval

E-value

ISG20

cd06149

DEDDh 3'-5' exonuclease domain of Interferon Stimulated Gene product of 20 kDa, and similar ...

33-121

2.85e-56

Pssm-ID: 99852 Cd Length: 157 Bit Score: 172.62 E-value: 2.85e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  33 GEILKILTGKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLNRKADCPENATMSLKHLTKKLLNRDIQVGKSGHSSVED 112
Cdd:cd06149   69 KEILKILKGKVVVGHAIHNDFKALKYFHPKHMTRDTSTIPLLNRKAGFPENCRVSLKVLAKRLLHRDIQVGRQGHSSVED 148


                 ....*....
gi 530365443 113 AQATMELYK 121
Cdd:cd06149  149 ARATMELYK 157

REX4_like

cd06144

DEDDh 3'-5' exonuclease domain of RNA exonuclease 4, XPMC2, Interferon Stimulated Gene product ...

28-121

6.91e-36

DEDDh 3'-5' exonuclease domain of RNA exonuclease 4, XPMC2, Interferon Stimulated Gene product of 20 kDa, and similar proteins; This subfamily is composed of RNA exonuclease 4 (REX4 or Rex4p), XPMC2, Interferon (IFN) Stimulated Gene product of 20 kDa (ISG20), and similar proteins. REX4 is involved in pre-rRNA processing. It controls the ratio between the two forms of 5.8S rRNA in yeast. XPMC2 is a Xenopus gene which was identified through its ability to correct a mitotic defect in fission yeast. The human homolog of XPMC2 (hPMC2) may be involved in angiotensin II-induced adrenal cell cycle progression and cell proliferation. ISG20 is an IFN-induced antiviral exonuclease with a strong preference for single-stranded RNA and minor activity towards single-stranded DNA. These proteins are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved 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. REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherchia coli RNase T.

Pssm-ID: 99847 Cd Length: 152 Bit Score: 120.70 E-value: 6.91e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  28 EHFKDG--------EILKILTGKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLNRKADCpenATMSLKHLTKKLLNRD 99
Cdd:cd06144   56 EHLKDApdfeevqkKVAELLKGRILVGHALKNDLKVLKLDHPKKLIRDTSKYKPLRKTAKG---KSPSLKKLAKQLLGLD 132

                         90       100
                 ....*....|....*....|..
gi 530365443 100 IQVGKsgHSSVEDAQATMELYK 121
Cdd:cd06144  133 IQEGE--HSSVEDARAAMRLYR 152

REX1_like

cd06145

DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This ...

34-121

5.52e-24

DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This subfamily is composed of RNA exonuclease 1 (REX1 or Rex1p), REX3 (or Rex3p), and similar eukaryotic proteins. In yeast, REX1 and REX3 are required for 5S rRNA and MRP (mitochondrial RNA processing) RNA maturation, respectively. They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved 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. REX1 is the major exonuclease responsible for pre-tRNA trail trimming and may also be involved in nuclear CCA turnover. REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherichia coli RNase T.

Pssm-ID: 99848 Cd Length: 150 Bit Score: 90.24 E-value: 5.52e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  34 EILKILT-GKIVVGHAIHNDFKALQYFHPKSLtrDTSHIPPLNRKAdcpeNATMSLKHLTKKLLNRDIQVGKSGHSSVED 112
Cdd:cd06145   68 KLLSLISpDTILVGHSLENDLKALKLIHPRVI--DTAILFPHPRGP----PYKPSLKNLAKKYLGRDIQQGEGGHDSVED 141


                 ....*....
gi 530365443 113 AQATMELYK 121
Cdd:cd06145  142 ARAALELVK 150

DEDDh_RNase

cd06137

DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonucleases PAN2, RNA exonuclease (REX) ...

34-120

6.36e-19

DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonucleases PAN2, RNA exonuclease (REX)-1,-3, and -4, ISG20, and similar proteins; This group is composed of eukaryotic exoribonucleases that include PAN2, RNA exonuclease 1 (REX1 or Rex1p), REX3 (Rex3p), REX4 (or Rex4p), ISG20, and similar proteins. They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved 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. PAN2 is the catalytic subunit of poly(A) nuclease (PAN), a Pab1p-dependent 3'-5' exoribonuclease which plays an important role in the posttranscriptional maturation of pre-mRNAs. REX proteins are required for the processing and maturation of many RNA species, and ISG20 is an interferon-induced antiviral exonuclease with a strong preference for single-stranded RNA.

Pssm-ID: 99840 Cd Length: 161 Bit Score: 77.32 E-value: 6.36e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  34 EILKILTGK-IVVGHAIHNDFKALQYFHPKSLtrDTSHIPPLNRKADCPENaTMSLKHLTKKLLNRDIQVGKSGHSSVED 112
Cdd:cd06137   76 ALWKFIDPDtILVGHSLQNDLDALRMIHTRVV--DTAILTREAVKGPLAKR-QWSLRTLCRDFLGLKIQGGGEGHDSLED 152


                 ....*...
gi 530365443 113 AQATMELY 120
Cdd:cd06137  153 ALAAREVV 160

EXOIII

smart00479

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

34-128

4.38e-15

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

Pssm-ID: 214685 [Multi-domain] Cd Length: 169 Bit Score: 67.71 E-value: 4.38e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443    34 EILKILTGK-IVVGHAIHNDFKALQYFHPK--------SLTRDTSHIpplnRKADCPENATMSLKHLTKKLLNRDIQvgk 104
Cdd:smart00479  73 ELLEFLRGRiLVAGNSAHFDLRFLKLEHPRlgikqppkLPVIDTLKL----ARATNPGLPKYSLKKLAKRLLLEVIQ--- 145

                           90       100
                   ....*....|....*....|....
gi 530365443   105 SGHSSVEDAQATMELYKLVEVEWE 128
Cdd:smart00479 146 RAHRALDDARATAKLFKKLLERLE 169

PAN2_exo

cd06143

DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonuclease PAN2; PAN2 is the catalytic ...

41-121

5.18e-14

DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonuclease PAN2; PAN2 is the catalytic subunit of poly(A) nuclease (PAN), a Pab1p-dependent 3'-5' exoribonuclease which plays an important role in the posttranscriptional maturation of pre-mRNAs. PAN catalyzes the deadenylation of poly(A) tails, which are initially synthesized to default lengths of 70 to 90, to mRNA-specific lengths of 55 to 71. Pab1p and PAN also play a role in the export and decay of mRNA. PAN2 contains a DEDDh-type DnaQ-like 3'-5' exonuclease domain with three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved 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.

Pssm-ID: 99846 Cd Length: 174 Bit Score: 64.95 E-value: 5.18e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530365443  41 GKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLnrkadcPENATMSLKHLTKKLLNRDIQVGksGHSSVEDAQATMELY 120
Cdd:cd06143  102 GCIFVGHGLAKDFRVINIQVPKEQVIDTVELFHL------PGQRKLSLRFLAWYLLGEKIQSE--THDSIEDARTALKLY 173


                 .
gi 530365443 121 K 121
Cdd:cd06143  174 R 174

WRN_exo

cd06141

DEDDy 3'-5' exonuclease domain of WRN and similar proteins; WRN is a unique RecQ DNA helicase ...

32-105

2.21e-03

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.

Pssm-ID: 176653 [Multi-domain] Cd Length: 170 Bit Score: 36.02 E-value: 2.21e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530365443  32 DGEILKiltgkivVGHAIHNDFKALQYFHPKSL--TRDTSHIPPLNRkadcPENATMSLKHLTKKLLNRDIQVGKS 105
Cdd:cd06141   71 DPSILK-------VGVGIKGDARKLARDFGIEVrgVVDLSHLAKRVG----PRRKLVSLARLVEEVLGLPLSKPKK 135

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