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Conserved domains on  [gi|525345319|ref|NP_001266278|]
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RNA exonuclease 4 isoform 2 [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 ...
 114-222 5.40e-52

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 cd06144:

Pssm-ID: 447876  Cd Length: 152  Bit Score: 165.77  E-value: 5.40e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319 114 TSSIRSGKLRRQPQphppreeLEVVQKEVAEMLKGRILVGHALHNDLKVLFLDHPKKKIRDTQKYKPFKSQVKSGRPSLR 193
Cdd:cd06144   50 VSGIRPEHLKDAPD-------FEEVQKKVAELLKGRILVGHALKNDLKVLKLDHPKKLIRDTSKYKPLRKTAKGKSPSLK 122

                         90       100
                 ....*....|....*....|....*....
gi 525345319 194 LLSEKILGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:cd06144  123 KLAKQLLGLDIQEGEHSSVEDARAAMRLY 151
 
Name Accession Description Interval E-value
REX4_like cd06144
DEDDh 3'-5' exonuclease domain of RNA exonuclease 4, XPMC2, Interferon Stimulated Gene product ...
 114-222 5.40e-52

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: 165.77  E-value: 5.40e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319 114 TSSIRSGKLRRQPQphppreeLEVVQKEVAEMLKGRILVGHALHNDLKVLFLDHPKKKIRDTQKYKPFKSQVKSGRPSLR 193
Cdd:cd06144   50 VSGIRPEHLKDAPD-------FEEVQKKVAELLKGRILVGHALKNDLKVLKLDHPKKLIRDTSKYKPLRKTAKGKSPSLK 122

                         90       100
                 ....*....|....*....|....*....
gi 525345319 194 LLSEKILGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:cd06144  123 KLAKQLLGLDIQEGEHSSVEDARAAMRLY 151
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 115-230 1.42e-20

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


Pssm-ID: 214685 [Multi-domain]  Cd Length: 169  Bit Score: 85.43  E-value: 1.42e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319   115 SSIRSGKLRRQPqphppreELEVVQKEVAEMLKGRILV-GHALHNDLKVLFLDHPKKK--------IRDTQKYKPFKSQV 185
Cdd:smart00479  54 HGITPEMLDDAP-------TFEEVLEELLEFLRGRILVaGNSAHFDLRFLKLEHPRLGikqppklpVIDTLKLARATNPG 126

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 525345319   186 KsGRPSLRLLSEKiLGLQVQQAEHCSIQDAQAAMRLYVMVKKEWE 230
Cdd:smart00479 127 L-PKYSLKKLAKR-LLLEVIQRAHRALDDARATAKLFKKLLERLE 169
RNase_T pfam00929
Exonuclease; This family includes a variety of exonuclease proteins, such as ribonuclease T ...
 130-222 1.13e-07

Exonuclease; This family includes a variety of exonuclease proteins, such as ribonuclease T and the epsilon subunit of DNA polymerase III.;


Pssm-ID: 395743 [Multi-domain]  Cd Length: 164  Bit Score: 50.04  E-value: 1.13e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319  130 PPREELEVVQKEVAEMLKG---------RILVGHALHNDLKVLFLDHPKkkIRDTQKYKPFKSQVKSGRPSLRL--LSEK 198
Cdd:pfam00929  64 DNKPSFEEVLEEFLEFLRKgnllvahnaSFDVGFLRYDDKRFLKKPMPK--LNPVIDTLILDKATYKELPGRSLdaLAEK 141

                          90       100
                  ....*....|....*....|....
gi 525345319  199 iLGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:pfam00929 142 -LGLEHIGRAHRALDDARATAKLF 164
 
Name Accession Description Interval E-value
REX4_like cd06144
DEDDh 3'-5' exonuclease domain of RNA exonuclease 4, XPMC2, Interferon Stimulated Gene product ...
 114-222 5.40e-52

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: 165.77  E-value: 5.40e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319 114 TSSIRSGKLRRQPQphppreeLEVVQKEVAEMLKGRILVGHALHNDLKVLFLDHPKKKIRDTQKYKPFKSQVKSGRPSLR 193
Cdd:cd06144   50 VSGIRPEHLKDAPD-------FEEVQKKVAELLKGRILVGHALKNDLKVLKLDHPKKLIRDTSKYKPLRKTAKGKSPSLK 122

                         90       100
                 ....*....|....*....|....*....
gi 525345319 194 LLSEKILGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:cd06144  123 KLAKQLLGLDIQEGEHSSVEDARAAMRLY 151
ISG20 cd06149
DEDDh 3'-5' exonuclease domain of Interferon Stimulated Gene product of 20 kDa, and similar ...
 136-222 1.04e-20

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: 85.57  E-value: 1.04e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319 136 EVVQKEVAEMLKGRILVGHALHNDLKVLFLDHPKKKIRDTQKYKPFKSQVK---SGRPSLRLLSEKIL--GLQVQQAEHC 210
Cdd:cd06149   65 AVAQKEILKILKGKVVVGHAIHNDFKALKYFHPKHMTRDTSTIPLLNRKAGfpeNCRVSLKVLAKRLLhrDIQVGRQGHS 144

                         90
                 ....*....|..
gi 525345319 211 SIQDAQAAMRLY 222
Cdd:cd06149  145 SVEDARATMELY 156
EXOIII smart00479
exonuclease domain in DNA-polymerase alpha and epsilon chain, ribonuclease T and other ...
 115-230 1.42e-20

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


Pssm-ID: 214685 [Multi-domain]  Cd Length: 169  Bit Score: 85.43  E-value: 1.42e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319   115 SSIRSGKLRRQPqphppreELEVVQKEVAEMLKGRILV-GHALHNDLKVLFLDHPKKK--------IRDTQKYKPFKSQV 185
Cdd:smart00479  54 HGITPEMLDDAP-------TFEEVLEELLEFLRGRILVaGNSAHFDLRFLKLEHPRLGikqppklpVIDTLKLARATNPG 126

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 525345319   186 KsGRPSLRLLSEKiLGLQVQQAEHCSIQDAQAAMRLYVMVKKEWE 230
Cdd:smart00479 127 L-PKYSLKKLAKR-LLLEVIQRAHRALDDARATAKLFKKLLERLE 169
REX1_like cd06145
DEDDh 3'-5' exonuclease domain of RNA exonuclease 1, -3 and similar eukaryotic proteins; This ...
 135-221 2.91e-20

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: 84.07  E-value: 2.91e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319 135 LEVVQKEVAEML-KGRILVGHALHNDLKVLFLDHPkkKIRDT------QKYKPFKsqvksgrPSLRLLSEKILGLQVQQ- 206
Cdd:cd06145   62 LEDVQKKLLSLIsPDTILVGHSLENDLKALKLIHP--RVIDTailfphPRGPPYK-------PSLKNLAKKYLGRDIQQg 132

                         90
                 ....*....|....*.
gi 525345319 207 -AEHCSIQDAQAAMRL 221
Cdd:cd06145  133 eGGHDSVEDARAALEL 148
PAN2_exo cd06143
DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonuclease PAN2; PAN2 is the catalytic ...
 148-222 6.70e-16

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: 73.03  E-value: 6.70e-16
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 525345319 148 GRILVGHALHNDLKVLFLDHPKKKIRDTQK--YKPfksqvKSGRPSLRLLSEKILGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:cd06143  102 GCIFVGHGLAKDFRVINIQVPKEQVIDTVElfHLP-----GQRKLSLRFLAWYLLGEKIQSETHDSIEDARTALKLY 173
DEDDh_RNase cd06137
DEDDh 3'-5' exonuclease domain of the eukaryotic exoribonucleases PAN2, RNA exonuclease (REX) ...
 150-222 2.42e-09

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: 54.59  E-value: 2.42e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 525345319 150 ILVGHALHNDLKVLFLDHPkkKIRDTqkYKPFKSQVK----SGRPSLRLLSEKILGLQVQQAE--HCSIQDAQAAMRLY 222
Cdd:cd06137   86 ILVGHSLQNDLDALRMIHT--RVVDT--AILTREAVKgplaKRQWSLRTLCRDFLGLKIQGGGegHDSLEDALAAREVV 160
RNase_T pfam00929
Exonuclease; This family includes a variety of exonuclease proteins, such as ribonuclease T ...
 130-222 1.13e-07

Exonuclease; This family includes a variety of exonuclease proteins, such as ribonuclease T and the epsilon subunit of DNA polymerase III.;


Pssm-ID: 395743 [Multi-domain]  Cd Length: 164  Bit Score: 50.04  E-value: 1.13e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525345319  130 PPREELEVVQKEVAEMLKG---------RILVGHALHNDLKVLFLDHPKkkIRDTQKYKPFKSQVKSGRPSLRL--LSEK 198
Cdd:pfam00929  64 DNKPSFEEVLEEFLEFLRKgnllvahnaSFDVGFLRYDDKRFLKKPMPK--LNPVIDTLILDKATYKELPGRSLdaLAEK 141

                          90       100
                  ....*....|....*....|....
gi 525345319  199 iLGLQVQQAEHCSIQDAQAAMRLY 222
Cdd:pfam00929 142 -LGLEHIGRAHRALDDARATAKLF 164
 
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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