P78549 (NTHL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endonuclease III-like protein 1
EC=4.2.99.18

Gene names

Name:	NTHL1
Synonyms:	NTH1, OCTS3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	4Fe-4S Iron Iron-sulfur Metal-binding
Molecular function	Glycosidase Hydrolase Lyase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	depyrimidination Traceable author statement. Source: Reactome nucleotide-excision repair, DNA incision, 5'-to lesion Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	mitochondrion Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW DNA N-glycosylase activity Inferred from direct assay Ref.8. Source: UniProtKB DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay Ref.1. Source: UniProtKB double-stranded DNA binding Inferred from direct assay PubMed 15358233. Source: UniProtKB endonuclease activity Traceable author statement Ref.2. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 312	312	Endonuclease III-like protein 1		PRO_0000102227
Sites
	Active site	220	1	Nucleophile; for N-glycosylase activity Ref.5
	Metal binding	290	1	Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
	Metal binding	297	1	Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
	Metal binding	300	1	Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
	Metal binding	306	1	Iron-sulfur (4Fe-4S) By similarity UniProtKB P20625
Amino acid modifications
	Modified residue	71	1	Phosphoserine Ref.11 Ref.12
	Modified residue	73	1	Phosphoserine Ref.12
Natural variations
	Natural variant	21	1	R → W. Ref.3 Corresponds to variant rs3087469 [ dbSNP | Ensembl ].		VAR_016125
	Natural variant	33	1	R → K. Corresponds to variant rs2302172 [ dbSNP | Ensembl ].		VAR_016126
	Natural variant	176	1	I → T. Corresponds to variant rs1805378 [ dbSNP | Ensembl ].		VAR_016127
	Natural variant	234	1	S → L. Ref.3 Corresponds to variant rs3211977 [ dbSNP | Ensembl ].		VAR_029318
	Natural variant	239	1	D → Y. Corresponds to variant rs3087468 [ dbSNP | Ensembl ].		VAR_016128
Experimental info
	Mutagenesis	220	1	K → Q: Inactivates enzyme. Ref.5
	Mutagenesis	220	1	K → R: 85-fold reduction in activity. Ref.5
	Sequence conflict	9 – 10	2	MT → TS in CAA70865. Ref.8
	Sequence conflict	78	1	Missing in CAA70865. Ref.8
	Sequence conflict	151	1	M → I in AAB41534. Ref.1
	Sequence conflict	160	1	T → A in AAB41534. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P78549 [UniParc]. Last modified May 1, 1999. Version 2. Checksum: 379816A1E0B45050	FASTA	312	34,390
	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

References

	« Hide 'large scale' referencesShow '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. , 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

NIEHS-SNPs

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.
IPI	IPI00001722.
RefSeq	NP_002519.1. NM_002528.5.
UniGene	Hs.66196.
3D structure databases
ProteinModelPortal	P78549.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000219066.
PTM databases
PhosphoSite	P78549.
Polymorphism databases
DMDM	29840795.
Proteomic databases
PaxDb	P78549.
PRIDE	P78549.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219066; ENSP00000219066; ENSG00000065057.
GeneID	4913.
KEGG	hsa:4913.
UCSC	uc002col.1. human.
Organism-specific databases
CTD	4913.
GeneCards	GC16M002089.
HGNC	HGNC:8028. NTHL1.
HPA	CAB025152.
MIM	602656. gene.
neXtProt	NX_P78549.
PharmGKB	PA31811.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0177.
HOGENOM	HOG000252209.
HOVERGEN	HBG052675.
InParanoid	P78549.
KO	K10773.
OMA	CLNQALC.
OrthoDB	EOG4933JH.
PhylomeDB	P78549.
Enzyme and pathway databases
BRENDA	4.2.99.18. 2681.
Reactome	REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	P78549.
Bgee	P78549.
CleanEx	HS_NTHL1.
Genevestigator	P78549.
GermOnline	ENSG00000065057. Homo sapiens.
Family and domain databases
Gene3D	1.10.1670.10. 1 hit. 1.10.340.30. 1 hit.
InterPro	IPR011257. 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]
Pfam	PF00633. HHH. 1 hit. PF00730. HhH-GPD. 1 hit. [Graphical view]
SMART	SM00478. ENDO3c. 1 hit. SM00525. FES. 1 hit. [Graphical view]
SUPFAM	SSF48150. DNA_glycsylse. 1 hit.
PROSITE	PS00764. ENDONUCLEASE_III_1. False negative. PS01155. ENDONUCLEASE_III_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4913.
NextBio	18903.
SOURCE	Search...

Entry information

Entry name

NTHL1_HUMAN

Accession

Primary (citable) accession number: P78549
Secondary accession number(s): Q1MVR1 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.