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P31378

- NTH1_YEAST

UniProt

P31378 - NTH1_YEAST

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Protein
Endonuclease III homolog 1
Gene
NTG1, OGG2, SCR1, YAL015C, FUN33
Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.13 Publications

Catalytic activityi

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.3 Publications

Kineticsi

  1. KM=227 nM for dihydrouracil containing duplex oligonucleotides (N-glycosylase activity)3 Publications
  2. KM=250 nM for 5-hydroxy-6-hydrothymine containing duplex oligonucleotides (N-glycosylase activity)
  3. KM=721 nM for 5-hydroxy-6-hydrouracil containing duplex oligonucleotides (N-glycosylase activity)
  4. KM=755 nM for 5-hydroxy-5-methylhydantoin containing duplex oligonucleotides (N-glycosylase activity)
  5. KM=997 nM for 5-hydroxyuracil containing duplex oligonucleotides (N-glycosylase activity)
  6. KM=1380 nM for 5-hydroxycytosine containing duplex oligonucleotides (N-glycosylase activity)
  7. KM=3250 nM for thymine glycol containing duplex oligonucleotides (N-glycosylase activity)
  8. KM=1305 nM for 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyAde) containing duplex oligonucleotides (N-glycosylase activity)
  9. KM=2460 nM for 4,6-diamino-5-formamidopyrimidine (FapyGua) containing duplex oligonucleotides (N-glycosylase activity)
  10. KM=24.86 nM for AP/G abasic-site containing duplex oligonucleotides (AP lyase activity)
  11. KM=11.37 nM for AP/A abasic-site containing duplex oligonucleotides (AP lyase activity)
  12. KM=6.67 nM for AP/T abasic-site containing duplex oligonucleotides (AP lyase activity)
  13. 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)

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei243 – 2431Nucleophile; for N-glycosylase activity By similarity
Sitei262 – 2621Important for catalytic activity By similarity

GO - Molecular functioni

  1. DNA binding Source: InterPro
  2. DNA-(apurinic or apyrimidinic site) lyase activity Source: SGD
  3. oxidized purine nucleobase lesion DNA N-glycosylase activity Source: SGD
  4. oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity Source: SGD
Complete GO annotation...

GO - Biological processi

  1. DNA catabolic process, endonucleolytic Source: GOC
  2. DNA repair Source: SGD
  3. base-excision repair Source: SGD
  4. base-excision repair, AP site formation Source: SGD
  5. cellular response to oxidative stress Source: SGD
  6. positive regulation of mitochondrial DNA replication Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase, Lyase

Keywords - Biological processi

DNA damage, DNA repair

Enzyme and pathway databases

BioCyciYEAST:G3O-28827-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:NTG1
Synonyms:OGG2, SCR1
Ordered Locus Names:YAL015C
ORF Names:FUN33
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
ProteomesiUP000002311: Chromosome I

Organism-specific databases

CYGDiYAL015c.
SGDiS000000013. NTG1.

Subcellular locationi

Nucleus. Mitochondrion
Note: Relocalizes to organelles containing elevated oxidative DNA damage.4 Publications

GO - Cellular componenti

  1. mitochondrion Source: SGD
  2. nucleus Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi3 – 64KISK → EISE in NTG1(mts); reduces mitochondrial localization by 40%. 1 Publication
Mutagenesisi15 – 162KR → AA in NTG1(nls1); reduces nuclear localization by 60%.
Mutagenesisi33 – 342KR → AA in NTG1(nls2); reduces nuclear localization by 60%.
Mutagenesisi243 – 2431K → Q: Abolishes cleavage of substrate oligonucleotides. 1 Publication
Mutagenesisi364 – 3641K → R: Cannot properly relocalize in response to oxidative stress. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2626Mitochondrion Reviewed prediction
Add
BLAST
Chaini27 – 399373Endonuclease III homolog 1UniRule annotation
PRO_0000001744Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki194 – 194Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Inferred

Post-translational modificationi

Monosumoylated. Sumoylation is associated with targeting of NTG1 to nuclei containing oxidative DNA damage.1 Publication

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiP31378.
PaxDbiP31378.

Expressioni

Inductioni

By oxidizing agents.3 Publications

Gene expression databases

GenevestigatoriP31378.

Interactioni

Protein-protein interaction databases

BioGridi31751. 39 interactions.
DIPiDIP-6614N.
MINTiMINT-673918.
STRINGi4932.YAL015C.

Structurei

3D structure databases

ProteinModelPortaliP31378.
SMRiP31378. Positions 144-318.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini223 – 24725HhH
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi14 – 3724Bipartite nuclear localization signal Reviewed prediction
Add
BLAST

Sequence similaritiesi

Belongs to the Nth/MutY family.
Contains 1 HhH domain.

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0177.
GeneTreeiENSGT00510000047513.
HOGENOMiHOG000252209.
KOiK10773.
OMAiLNIMRYC.
OrthoDBiEOG7PK99N.

Family and domain databases

Gene3Di1.10.1670.10. 1 hit.
1.10.340.30. 1 hit.
HAMAPiMF_03183. Endonuclease_III_Nth.
InterProiIPR011257. DNA_glycosylase.
IPR004036. Endonuclease-III-like_CS2.
IPR003265. HhH-GPD_domain.
IPR000445. HhH_motif.
IPR023170. HTH_base_excis_C.
[Graphical view]
PfamiPF00633. HHH. 1 hit.
PF00730. HhH-GPD. 1 hit.
[Graphical view]
SMARTiSM00478. ENDO3c. 1 hit.
[Graphical view]
SUPFAMiSSF48150. SSF48150. 1 hit.
PROSITEiPS01155. ENDONUCLEASE_III_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P31378-1 [UniParc]FASTAAdd to Basket

« Hide

MQKISKYSSM AILRKRPLVK TETGPESELL PEKRTKIKQE EVVPQPVDID    50
WVKSLPNKQY FEWIVVRNGN VPNRWATPLD PSILVTPAST KVPYKFQETY 100
ARMRVLRSKI LAPVDIIGGS SIPVTVASKC GISKEQISPR DYRLQVLLGV 150
MLSSQTKDEV TAMAMLNIMR YCIDELHSEE GMTLEAVLQI NETKLDELIH 200
SVGFHTRKAK YILSTCKILQ DQFSSDVPAT INELLGLPGV GPKMAYLTLQ 250
KAWGKIEGIC VDVHVDRLTK LWKWVDAQKC KTPDQTRTQL QNWLPKGLWT 300
EINGLLVGFG QIITKSRNLG DMLQFLPPDD PRSSLDWDLQ SQLYKEIQQN 350
IMSYPKWVKY LEGKRELNVE AEINVKHEEK TVEETMVKLE NDISVKVED 399
Length:399
Mass (Da):45,577
Last modified:July 1, 1993 - v1
Checksum:iA3C878A3004908F3
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05146 Genomic DNA. Translation: AAC04942.1.
BK006935 Genomic DNA. Translation: DAA06973.1.
PIRiS36719.
RefSeqiNP_009387.1. NM_001178160.1.

Genome annotation databases

EnsemblFungiiYAL015C; YAL015C; YAL015C.
GeneIDi851218.
KEGGisce:YAL015C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05146 Genomic DNA. Translation: AAC04942.1 .
BK006935 Genomic DNA. Translation: DAA06973.1 .
PIRi S36719.
RefSeqi NP_009387.1. NM_001178160.1.

3D structure databases

ProteinModelPortali P31378.
SMRi P31378. Positions 144-318.
ModBasei Search...

Protein-protein interaction databases

BioGridi 31751. 39 interactions.
DIPi DIP-6614N.
MINTi MINT-673918.
STRINGi 4932.YAL015C.

Proteomic databases

MaxQBi P31378.
PaxDbi P31378.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblFungii YAL015C ; YAL015C ; YAL015C .
GeneIDi 851218.
KEGGi sce:YAL015C.

Organism-specific databases

CYGDi YAL015c.
SGDi S000000013. NTG1.

Phylogenomic databases

eggNOGi COG0177.
GeneTreei ENSGT00510000047513.
HOGENOMi HOG000252209.
KOi K10773.
OMAi LNIMRYC.
OrthoDBi EOG7PK99N.

Enzyme and pathway databases

BioCyci YEAST:G3O-28827-MONOMER.

Miscellaneous databases

NextBioi 968109.

Gene expression databases

Genevestigatori P31378.

Family and domain databases

Gene3Di 1.10.1670.10. 1 hit.
1.10.340.30. 1 hit.
HAMAPi MF_03183. Endonuclease_III_Nth.
InterProi IPR011257. DNA_glycosylase.
IPR004036. Endonuclease-III-like_CS2.
IPR003265. HhH-GPD_domain.
IPR000445. HhH_motif.
IPR023170. HTH_base_excis_C.
[Graphical view ]
Pfami PF00633. HHH. 1 hit.
PF00730. HhH-GPD. 1 hit.
[Graphical view ]
SMARTi SM00478. ENDO3c. 1 hit.
[Graphical view ]
SUPFAMi SSF48150. SSF48150. 1 hit.
PROSITEi PS01155. ENDONUCLEASE_III_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  4. 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.

Entry informationi

Entry nameiNTH1_YEAST
AccessioniPrimary (citable) accession number: P31378
Secondary accession number(s): D6VPK3
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Does not possess a consensus sequence for a C-terminal iron-sulfur center typical of all other endonuclease III homologs (1 Publication).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  3. Yeast chromosome I
    Yeast (Saccharomyces cerevisiae) chromosome I: entries and gene names

External Data

Dasty 3

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