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P78549 (NTHL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Endonuclease III-like protein 1

EC=4.2.99.18
Gene names
Name:NTHL1
Synonyms:NTH1, OCTS3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length312 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has both an apurinic and/or apyrimidinic endonuclease activity and a DNA N-glycosylase activity. Incises damaged DNA at cytosines, thymines and guanines. Acts on a damaged strand, 5' from the damaged site. Required for the repair of both oxidative DNA damage and spontaneous mutagenic lesions. Ref.1 Ref.5 Ref.6 Ref.8

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. UniProtKB P20625

Cofactor

Binds 1 4Fe-4S cluster. The cluster is not important for the catalytic activity, but is probably involved in the proper positioning of the enzyme along the DNA strand.

Subcellular location

Nucleus Ref.8 Ref.9.

Tissue specificity

Widely expressed with highest levels in heart and lowest levels in lung and liver. Ref.1 Ref.2 Ref.8

Developmental stage

Expression levels are regulated during the cell cycle with increased levels during early and mid S-phase. Ref.8

Sequence similarities

Belongs to the Nth/MutY family.

Caution

It is uncertain whether Met-1, Met-9 or Met-16 is the initiator.

Sequence caution

The sequence AAC51136.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH03014.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA19413.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA32695.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 312312Endonuclease III-like protein 1
PRO_0000102227

Sites

Active site2201Nucleophile; for N-glycosylase activity Ref.5
Metal binding2901Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
Metal binding2971Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
Metal binding3001Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
Metal binding3061Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625

Amino acid modifications

Modified residue711Phosphoserine Ref.11 Ref.12
Modified residue731Phosphoserine Ref.12

Natural variations

Natural variant211R → W. Ref.3
Corresponds to variant rs3087469 [ dbSNP | Ensembl ].
VAR_016125
Natural variant331R → K.
Corresponds to variant rs2302172 [ dbSNP | Ensembl ].
VAR_016126
Natural variant1761I → T.
Corresponds to variant rs1805378 [ dbSNP | Ensembl ].
VAR_016127
Natural variant2341S → L. Ref.3
Corresponds to variant rs3211977 [ dbSNP | Ensembl ].
VAR_029318
Natural variant2391D → Y.
Corresponds to variant rs3087468 [ dbSNP | Ensembl ].
VAR_016128

Experimental info

Mutagenesis2201K → Q: Inactivates enzyme. Ref.5
Mutagenesis2201K → R: 85-fold reduction in activity. Ref.5
Sequence conflict9 – 102MT → TS in CAA70865. Ref.8
Sequence conflict781Missing in CAA70865. Ref.8
Sequence conflict1511M → I in AAB41534. Ref.1
Sequence conflict1601T → A in AAB41534. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P78549 [UniParc].

Last modified May 1, 1999. Version 2.
Checksum: 379816A1E0B45050

FASTA31234,390
        10         20         30         40         50         60 
MCSPQESGMT ALSARMLTRS RSLGPGAGPR GCREEPGPLR RREAAAEARK SHSPVKRPRK 

        70         80         90        100        110        120 
AQRLRVAYEG SDSEKGEGAE PLKVPVWEPQ DWQQQLVNIR AMRNKKDAPV DHLGTEHCYD 

       130        140        150        160        170        180 
SSAPPKVRRY QVLLSLMLSS QTKDQVTAGA MQRLRARGLT VDSILQTDDA TLGKLIYPVG 

       190        200        210        220        230        240 
FWRSKVKYIK QTSAILQQHY GGDIPASVAE LVALPGVGPK MAHLAMAVAW GTVSGIAVDT 

       250        260        270        280        290        300 
HVHRIANRLR WTKKATKSPE ETRAALEEWL PRELWHEING LLVGFGQQTC LPVHPRCHAC 

       310 
LNQALCPAAQ GL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III."
Aspinwall R., Rothwell D.G., Roldan-Arjona T., Anselmino C., Ward C.J., Cheadle J.P., Sampson J.R., Lindahl T., Harris P.C., Hickson I.D.
Proc. Natl. Acad. Sci. U.S.A. 94:109-114(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]"Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes."
Imai K., Sarker A.H., Akiyama K., Ikeda S., Yao M., Tsutsui K., Shohmori T., Seki S.
Gene 222:287-295(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
Tissue: Placenta.
[3]NIEHS SNPs program
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-21 AND LEU-234.
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue."
Ikeda S., Biswas T., Roy R., Izumi T., Boldogh I., Kurosky A., Sarker A.H., Seki S., Mitra S.
J. Biol. Chem. 273:21585-21593(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-312, FUNCTION, ACTIVE SITE, MUTAGENESIS OF LYS-220.
Tissue: Bone marrow.
[6]"Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III."
Hilbert T.P., Chaung W., Boorstein R.J., Cunningham R.P., Teebor G.W.
J. Biol. Chem. 272:6733-6740(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-312, FUNCTION.
Tissue: Spleen.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-312.
Tissue: Lung.
[8]"Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA."
Luna L., Bjoras M., Hoff E., Rognes T., Seeberg E.
Mutat. Res. 460:95-104(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-312, FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[9]"Differential intracellular localization of the human and mouse endonuclease III homologs and analysis of the sorting signals."
Ikeda S., Kohmoto T., Tabata R., Seki Y.
DNA Repair 1:847-854(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71 AND SER-73, MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U79718 mRNA. Translation: AAB41534.1.
AB014460 Genomic DNA. Translation: BAA32695.1. Different initiation.
AF498098 Genomic DNA. Translation: AAM11786.1.
AC005600 Genomic DNA. Translation: AAC34209.1.
AB001575 mRNA. Translation: BAA19413.1. Different initiation.
U81285 mRNA. Translation: AAC51136.1. Different initiation.
BC003014 mRNA. Translation: AAH03014.1. Different initiation.
BC000391 mRNA. Translation: AAH00391.2.
Y09687 mRNA. Translation: CAA70865.1.
IPIIPI00001722.
RefSeqNP_002519.1. NM_002528.5.
UniGeneHs.66196.

3D structure databases

ProteinModelPortalP78549.
ModBaseSearch...

Protein-protein interaction databases

STRING9606.ENSP00000219066.

PTM databases

PhosphoSiteP78549.

Polymorphism databases

DMDM29840795.

Proteomic databases

PaxDbP78549.
PRIDEP78549.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219066; ENSP00000219066; ENSG00000065057.
GeneID4913.
KEGGhsa:4913.
UCSCuc002col.1. human.

Organism-specific databases

CTD4913.
GeneCardsGC16M002089.
HGNCHGNC:8028. NTHL1.
HPACAB025152.
MIM602656. gene.
neXtProtNX_P78549.
PharmGKBPA31811.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0177.
HOGENOMHOG000252209.
HOVERGENHBG052675.
InParanoidP78549.
KOK10773.
OMACLNQALC.
OrthoDBEOG4933JH.
PhylomeDBP78549.

Enzyme and pathway databases

BRENDA4.2.99.18. 2681.
ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressP78549.
BgeeP78549.
CleanExHS_NTHL1.
GenevestigatorP78549.
GermOnlineENSG00000065057. Homo sapiens.

Family and domain databases

Gene3D1.10.1670.10. 1 hit.
1.10.340.30. 1 hit.
InterProIPR011257. DNA_glycosylase.
IPR004036. Endonuclease-III_CS2.
IPR003651. Endouclease3_FeS-loop_motif.
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.
SM00525. FES. 1 hit.
[Graphical view]
SUPFAMSSF48150. DNA_glycsylse. 1 hit.
PROSITEPS00764. ENDONUCLEASE_III_1. False negative.
PS01155. ENDONUCLEASE_III_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi4913.
NextBio18903.
SOURCESearch...

Entry information

Entry nameNTHL1_HUMAN
AccessionPrimary (citable) accession number: P78549
Secondary accession number(s): Q1MVR1 expand/collapse secondary AC list , Q99566, Q99794, Q9BPX2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: May 1, 1999
Last modified: May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families