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P31378

- NTH1_YEAST

UniProt

P31378 - NTH1_YEAST

Protein

Endonuclease III homolog 1

Gene

NTG1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Jul 1993)
      Previous versions | rss
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    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 PublicationsUniRule annotation

    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 Publications
    3. KM=721 nM for 5-hydroxy-6-hydrouracil containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    4. KM=755 nM for 5-hydroxy-5-methylhydantoin containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    5. KM=997 nM for 5-hydroxyuracil containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    6. KM=1380 nM for 5-hydroxycytosine containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    7. KM=3250 nM for thymine glycol containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    8. KM=1305 nM for 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyAde) containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    9. KM=2460 nM for 4,6-diamino-5-formamidopyrimidine (FapyGua) containing duplex oligonucleotides (N-glycosylase activity)3 Publications
    10. KM=24.86 nM for AP/G abasic-site containing duplex oligonucleotides (AP lyase activity)3 Publications
    11. KM=11.37 nM for AP/A abasic-site containing duplex oligonucleotides (AP lyase activity)3 Publications
    12. KM=6.67 nM for AP/T abasic-site containing duplex oligonucleotides (AP lyase activity)3 Publications
    13. KM=36.58 nM for AP/C abasic-site containing duplex oligonucleotides (AP lyase activity)3 Publications

    Vmax=1.9 nmol/min/ng enzyme for dihydrouracil containing duplex oligonucleotides (N-glycosylase activity)3 Publications

    Sites

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

    GO - Molecular functioni

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

    GO - Biological processi

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

    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 1UniRule annotation (EC:3.2.2.-UniRule annotation, EC:4.2.99.18UniRule annotation)
    Alternative name(s):
    Bifunctional DNA N-glycoslyase/DNA-(apurinic or apyrimidinic site) lyase 1UniRule annotation
    Short name:
    DNA glycoslyase/AP lyase 1UniRule annotation
    Endonuclease III-like glycosylase 1
    Redoxyendonuclease 1
    Gene namesi
    Name:NTG1UniRule annotation
    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.

    GO - Cellular componenti

    1. mitochondrion Source: SGD
    2. nucleus Source: SGD

    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%.
    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 – 2626MitochondrionUniRule annotationAdd
    BLAST
    Chaini27 – 399373Endonuclease III homolog 1PRO_0000001744Add
    BLAST

    Amino acid modifications

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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini223 – 24725HhHUniRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi14 – 3724Bipartite nuclear localization signalSequence AnalysisAdd
    BLAST

    Sequence similaritiesi

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

    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

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    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 122 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