Endonuclease III-like protein 1 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P78549 (NTHL1_HUMAN)

Last modified November 25, 2008. Version 83. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.
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.
Cofactor	Binds 1 4Fe-4S cluster. The cluster is not important for the catalytic activity, but which is probably involved in the proper positioning of the enzyme along the DNA strand.
Subcellular location	Nucleus.
Tissue specificity	Widely expressed with highest levels in heart and lowest levels in lung and liver.
Developmental stage	Expression levels are regulated during the cell cycle with increased levels during early and mid S-phase.
Sequence similarities	Belongs to the nth/mutY family.
Caution	It is uncertain whether Met-1, Met-9 or Met-16 is the initiator.

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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
Gene Ontology (GO)
Biological process	depyrimidination Inferred from Experiment. Source: Reactome nucleotide-excision repair, DNA incision, 5'-to lesion Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: InterPro double-stranded DNA binding Inferred from direct assay. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidized pyrimidine base lesion DNA N-glycosylase activity Inferred from Experiment. Source: Reactome protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
GAPDHS	O14556	1	EBI-1049350,EBI-1057431
MYH7	P12883	1	EBI-1049350,EBI-519141
NUDT1	P36639	1	EBI-1049350,EBI-1048967
RNMTL1	Q9HC36	1	EBI-1049350,EBI-1045440

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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

Nucleophile; for N-glycosylase activity

Metal binding

290

Iron-sulfur (4Fe-4S) By similarity

Metal binding

297

Iron-sulfur (4Fe-4S) By similarity

Metal binding

300

Iron-sulfur (4Fe-4S) By similarity

Metal binding

306

Iron-sulfur (4Fe-4S) By similarity

Natural variations

Natural variant

R → W: dbSNP rs3087469.

VAR_016125

Natural variant

R → K: dbSNP rs2302172.

VAR_016126

Natural variant

176

I → T: dbSNP rs1805378.

VAR_016127

Natural variant

234

S → L: dbSNP rs3211977.

VAR_029318

Natural variant

239

D → Y: dbSNP rs3087468.

VAR_016128

Experimental info

Mutagenesis

220

K → Q: Inactivates enzyme

Mutagenesis

220

K → R: 85-fold reduction in activity

Sequence conflict

9 – 10

MT → TS in CAA70865. Ref.8

Sequence conflict

Missing in CAA70865. Ref.8

Sequence conflict

151

M → I in AAB41534. Ref.1

Sequence conflict

160

T → A in AAB41534. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

P78549-1 [UniParc].

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

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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: 8990169] [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: 9831664] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY. Tissue: Placenta.
[3]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P., Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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. Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [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: 9705289] [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: 9045706] [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: 15489334] [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: 10882850] [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: 12531031] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	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.
RefSeq	NP_002519.1.
UniGene	Hs.66196
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P78549.
PTM databases
PhosphoSite	P78549.
Polymorphism databases
NIEHS-SNPs	Search...
Genome annotation databases
Ensembl	ENSG00000065057. Homo sapiens. [Contig view]
GeneID	4913.
KEGG	hsa:4913.
NMPDR	fig\|9606.3.peg.11540.
Organism-specific databases
H-InvDB	HIX0012711.
HGNC	HGNC:8028. NTHL1.
HPA	HPA008299.
MIM	602656. gene.
PharmGKB	PA31811.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P78549.
HOVERGEN	P78549.
Enzyme and pathway databases
Reactome	REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	P78549.
CleanEx	HS_NTHL1.
GermOnline	ENSG00000065057. Homo sapiens.
Family and domain databases
InterPro	IPR003265. Endo_3c. IPR004036. Endonuclease-III_CS2. IPR004035. Endouclease-III_FeS-bd_CS1. IPR003651. FeS_bd. IPR000445. HhH. [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]
PROSITE	PS00764. ENDONUCLEASE_III_1. False negative. PS01155. ENDONUCLEASE_III_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	18903.
SOURCE	Search...

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Entry information

Entry name

NTHL1_HUMAN

Accession

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

Q9BPX2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	May 1, 1999
Last modified:	November 25, 2008
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents