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P31378 (NTH1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endonuclease III homolog 1

EC=3.2.2.-
EC=4.2.99.18
Alternative name(s):
Bifunctional DNA N-glycoslyase/DNA-(apurinic or apyrimidinic site) lyase 1
Short name=DNA glycoslyase/AP lyase 1
Endonuclease III-like glycosylase 1
Redoxyendonuclease 1
Gene names
Name:NTG1
Synonyms:OGG2, SCR1
Ordered Locus Names:YAL015C
ORF Names:FUN33
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines, but also purine-derived lesions, alkylation damage and cytosine photoproducts generated by UV irradiation as well as abasic sites. Has also 8-oxoguanine DNA glycosylase activity. The AP lyase can incise AP sites opposite all four bases. May also play a role in the regulation of mtDNA copy number by introducing a double-stranded break (DSB) at the mtDNA replication origin ori5, initiating the rolling-circle mtDNA replication. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20

Catalytic activity

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. Ref.9 Ref.13 Ref.20

Subcellular location

Nucleus. Mitochondrion. Note: Relocalizes to organelles containing elevated oxidative DNA damage. Ref.11 Ref.12 Ref.18 Ref.20

Induction

By oxidizing agents. Ref.6 Ref.8 Ref.12

Post-translational modification

Monosumoylated. Sumoylation is associated with targeting of NTG1 to nuclei containing oxidative DNA damage. Ref.18

Disruption phenotype

Greatly increases spontaneous and hydrogen peroxide-induced mutation frequency. Causes mitochondrial genome instability. Suppresses mitochondrial point mutation rates, frameshifts and recombination rates, probably because NTG1 can generate mutagenic intermediates in yeast mitochondrial DNA. Ref.12 Ref.15 Ref.16

Miscellaneous

Does not possess a consensus sequence for a C-terminal iron-sulfur center typical of all other endonuclease III homologs (Ref.8).

Sequence similarities

Belongs to the Nth/MutY family.

Contains 1 HhH domain.

Biophysicochemical properties

Kinetic parameters:

KM=227 nM for dihydrouracil containing duplex oligonucleotides (N-glycosylase activity) Ref.8 Ref.10 Ref.13

KM=250 nM for 5-hydroxy-6-hydrothymine containing duplex oligonucleotides (N-glycosylase activity)

KM=721 nM for 5-hydroxy-6-hydrouracil containing duplex oligonucleotides (N-glycosylase activity)

KM=755 nM for 5-hydroxy-5-methylhydantoin containing duplex oligonucleotides (N-glycosylase activity)

KM=997 nM for 5-hydroxyuracil containing duplex oligonucleotides (N-glycosylase activity)

KM=1380 nM for 5-hydroxycytosine containing duplex oligonucleotides (N-glycosylase activity)

KM=3250 nM for thymine glycol containing duplex oligonucleotides (N-glycosylase activity)

KM=1305 nM for 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyAde) containing duplex oligonucleotides (N-glycosylase activity)

KM=2460 nM for 4,6-diamino-5-formamidopyrimidine (FapyGua) containing duplex oligonucleotides (N-glycosylase activity)

KM=24.86 nM for AP/G abasic-site containing duplex oligonucleotides (AP lyase activity)

KM=11.37 nM for AP/A abasic-site containing duplex oligonucleotides (AP lyase activity)

KM=6.67 nM for AP/T abasic-site containing duplex oligonucleotides (AP lyase activity)

KM=36.58 nM for AP/C abasic-site containing duplex oligonucleotides (AP lyase activity)

Vmax=1.9 nmol/min/ng enzyme for dihydrouracil containing duplex oligonucleotides (N-glycosylase activity)

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2626Mitochondrion Potential
Chain27 – 399373Endonuclease III homolog 1 HAMAP-Rule MF_03183
PRO_0000001744

Regions

Domain223 – 24725HhH
Motif14 – 3724Bipartite nuclear localization signal Potential

Sites

Active site2431Nucleophile; for N-glycosylase activity By similarity
Site2621Important for catalytic activity By similarity

Amino acid modifications

Cross-link194Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable

Experimental info

Mutagenesis3 – 64KISK → EISE in NTG1(mts); reduces mitochondrial localization by 40%. Ref.20
Mutagenesis15 – 162KR → AA in NTG1(nls1); reduces nuclear localization by 60%.
Mutagenesis33 – 342KR → AA in NTG1(nls2); reduces nuclear localization by 60%.
Mutagenesis2431K → Q: Abolishes cleavage of substrate oligonucleotides. Ref.20
Mutagenesis3641K → R: Cannot properly relocalize in response to oxidative stress. Ref.18

Sequences

Sequence LengthMass (Da)Tools
P31378 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: A3C878A3004908F3

FASTA39945,577
        10         20         30         40         50         60 
MQKISKYSSM AILRKRPLVK TETGPESELL PEKRTKIKQE EVVPQPVDID WVKSLPNKQY 

        70         80         90        100        110        120 
FEWIVVRNGN VPNRWATPLD PSILVTPAST KVPYKFQETY ARMRVLRSKI LAPVDIIGGS 

       130        140        150        160        170        180 
SIPVTVASKC GISKEQISPR DYRLQVLLGV MLSSQTKDEV TAMAMLNIMR YCIDELHSEE 

       190        200        210        220        230        240 
GMTLEAVLQI NETKLDELIH SVGFHTRKAK YILSTCKILQ DQFSSDVPAT INELLGLPGV 

       250        260        270        280        290        300 
GPKMAYLTLQ KAWGKIEGIC VDVHVDRLTK LWKWVDAQKC KTPDQTRTQL QNWLPKGLWT 

       310        320        330        340        350        360 
EINGLLVGFG QIITKSRNLG DMLQFLPPDD PRSSLDWDLQ SQLYKEIQQN IMSYPKWVKY 

       370        380        390 
LEGKRELNVE AEINVKHEEK TVEETMVKLE NDISVKVED 

« Hide

References

« Hide 'large scale' references
[1]"Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32 kb region between the LTE1 and SPO7 genes."
Ouellette B.F.F., Clark M.W., Keng T., Storms R.K., Zhong W.-W., Zeng B., Fortin N., Delaney S., Barton A.B., Kaback D.B., Bussey H.
Genome 36:32-42(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 204511 / S288c / AB972.
[2]"Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: analysis of the genes in the FUN38-MAK16-SPO7 region."
Barton A.B., Kaback D.B.
J. Bacteriol. 176:1872-1880(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 204511 / S288c / AB972.
[3]"The nucleotide sequence of chromosome I from Saccharomyces cerevisiae."
Bussey H., Kaback D.B., Zhong W.-W., Vo D.H., Clark M.W., Fortin N., Hall J., Ouellette B.F.F., Keng T., Barton A.B., Su Y., Davies C.J., Storms R.K.
Proc. Natl. Acad. Sci. U.S.A. 92:3809-3813(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[4]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[5]"Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily."
Nash H.M., Bruner S.D., Scharer O.D., Kawate T., Addona T.A., Spooner E., Lane W.S., Verdine G.L.
Curr. Biol. 6:968-980(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Base excision of oxidative purine and pyrimidine DNA damage in Saccharomyces cerevisiae by a DNA glycosylase with sequence similarity to endonuclease III from Escherichia coli."
Eide L., Bjoras M., Pirovano M., Alseth I., Berdal K.G., Seeberg E.
Proc. Natl. Acad. Sci. U.S.A. 93:10735-10740(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION BY DNA DAMAGE.
[7]"Purification, characterization, gene cloning, and expression of Saccharomyces cerevisiae redoxyendonuclease, a homolog of Escherichia coli endonuclease III."
Augeri L., Lee Y.M., Barton A.B., Doetsch P.W.
Biochemistry 36:721-729(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Saccharomyces cerevisiae possesses two functional homologues of Escherichia coli endonuclease III."
You H.J., Swanson R.L., Doetsch P.W.
Biochemistry 37:6033-6040(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBSTRATES, INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Repair of oxidatively damaged guanine in Saccharomyces cerevisiae by an alternative pathway."
Bruner S.D., Nash H.M., Lane W.S., Verdine G.L.
Curr. Biol. 8:393-403(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[10]"Substrate specificities of the ntg1 and ntg2 proteins of Saccharomyces cerevisiae for oxidized DNA bases are not identical."
Senturker S., Auffret van der Kemp P., You H.J., Doetsch P.W., Dizdaroglu M., Boiteux S.
Nucleic Acids Res. 26:5270-5276(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBSTRATES, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"Saccharomyces cerevisiae Ntg1p and Ntg2p: broad specificity N-glycosylases for the repair of oxidative DNA damage in the nucleus and mitochondria."
You H.J., Swanson R.L., Harrington C., Corbett A.H., Jinks-Robertson S., Sentuerker S., Wallace S.S., Boiteux S., Dizdaroglu M., Doetsch P.W.
Biochemistry 38:11298-11306(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]"The Saccharomyces cerevisiae homologues of endonuclease III from Escherichia coli, Ntg1 and Ntg2, are both required for efficient repair of spontaneous and induced oxidative DNA damage in yeast."
Alseth I., Eide L., Pirovano M., Rognes T., Seeberg E., Bjoras M.
Mol. Cell. Biol. 19:3779-3787(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OXIDATIVE DNA DAMAGE REPAIR, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INDUCTION.
[13]"Characterization of AP lyase activities of Saccharomyces cerevisiae Ntg1p and Ntg2p: implications for biological function."
Meadows K.L., Song B., Doetsch P.W.
Nucleic Acids Res. 31:5560-5567(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[14]"Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae."
Hanna M., Chow B.L., Morey N.J., Jinks-Robertson S., Doetsch P.W., Xiao W.
DNA Repair 3:51-59(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA ALKYLATION DAMAGE REPAIR.
[15]"Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae."
Doudican N.A., Song B., Shadel G.S., Doetsch P.W.
Mol. Cell. Biol. 25:5196-5204(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[16]"Ntg1p, the base excision repair protein, generates mutagenic intermediates in yeast mitochondrial DNA."
Phadnis N., Mehta R., Meednu N., Sia E.A.
DNA Repair 5:829-839(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[17]"Excision of the oxidatively formed 5-hydroxyhydantoin and 5-hydroxy-5-methylhydantoin pyrimidine lesions by Escherichia coli and Saccharomyces cerevisiae DNA N-glycosylases."
Gasparutto D., Muller E., Boiteux S., Cadet J.
Biochim. Biophys. Acta 1790:16-24(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OXIDATIVE DNA DAMAGE REPAIR, SUBSTRATES.
[18]"Dynamic compartmentalization of base excision repair proteins in response to nuclear and mitochondrial oxidative stress."
Griffiths L.M., Swartzlander D., Meadows K.L., Wilkinson K.D., Corbett A.H., Doetsch P.W.
Mol. Cell. Biol. 29:794-807(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUMOYLATION, MUTAGENESIS OF LYS-364.
[19]"Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication."
Hori A., Yoshida M., Shibata T., Ling F.
Nucleic Acids Res. 37:749-761(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTDNA REPLICATION.
[20]"Regulation of base excision repair: Ntg1 nuclear and mitochondrial dynamic localization in response to genotoxic stress."
Swartzlander D.B., Griffiths L.M., Lee J., Degtyareva N.P., Doetsch P.W., Corbett A.H.
Nucleic Acids Res. 38:3963-3974(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF 3-LYS--LYS-6; 15-LYS-ARG-16; 33-LYS-ARG-34 AND LYS-243.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L05146 Genomic DNA. Translation: AAC04942.1.
BK006935 Genomic DNA. Translation: DAA06973.1.
PIRS36719.
RefSeqNP_009387.1. NM_001178160.1.

3D structure databases

ProteinModelPortalP31378.
SMRP31378. Positions 144-318.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid31751. 39 interactions.
DIPDIP-6614N.
MINTMINT-673918.
STRING4932.YAL015C.

Proteomic databases

MaxQBP31378.
PaxDbP31378.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYAL015C; YAL015C; YAL015C.
GeneID851218.
KEGGsce:YAL015C.

Organism-specific databases

CYGDYAL015c.
SGDS000000013. NTG1.

Phylogenomic databases

eggNOGCOG0177.
GeneTreeENSGT00510000047513.
HOGENOMHOG000252209.
KOK10773.
OMALNIMRYC.
OrthoDBEOG7PK99N.

Enzyme and pathway databases

BioCycYEAST:G3O-28827-MONOMER.

Gene expression databases

GenevestigatorP31378.

Family and domain databases

Gene3D1.10.1670.10. 1 hit.
1.10.340.30. 1 hit.
HAMAPMF_03183. Endonuclease_III_Nth.
InterProIPR011257. DNA_glycosylase.
IPR004036. Endonuclease-III-like_CS2.
IPR003265. HhH-GPD_domain.
IPR000445. HhH_motif.
IPR023170. HTH_base_excis_C.
[Graphical view]
PfamPF00633. HHH. 1 hit.
PF00730. HhH-GPD. 1 hit.
[Graphical view]
SMARTSM00478. ENDO3c. 1 hit.
[Graphical view]
SUPFAMSSF48150. SSF48150. 1 hit.
PROSITEPS01155. ENDONUCLEASE_III_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio968109.

Entry information

Entry nameNTH1_YEAST
AccessionPrimary (citable) accession number: P31378
Secondary accession number(s): D6VPK3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: June 11, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome I

Yeast (Saccharomyces cerevisiae) chromosome I: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families