Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96FI4 (NEIL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endonuclease 8-like 1

EC=3.2.2.-
EC=4.2.99.18
Alternative name(s):
DNA glycosylase/AP lyase Neil1
DNA-(apurinic or apyrimidinic site) lyase Neil1
Endonuclease VIII-like 1
FPG1
Nei homolog 1
Short name=NEH1
Nei-like protein 1
Gene names
Name:NEIL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length390 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC. Ref.1 Ref.7 Ref.8 Ref.9

Catalytic activity

Removes damaged bases from DNA, leaving an abasic site.

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.

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Nucleus. Chromosome. Note: During mitosis, associates with centrosomes and condensed chromatin. Ref.10

Tissue specificity

Ubiquitous. Ref.8

Induction

Up-regulated during S-phase. Ref.8

Sequence similarities

Belongs to the FPG family.

RNA editing

Edited at position 242.
The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. The recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. Ref.11

Sequence caution

The sequence AK128372 differs from that shown. Reason: Erroneous CDS prediction.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentChromosome
Cytoplasm
Cytoskeleton
Nucleus
   Coding sequence diversityPolymorphism
RNA editing
   LigandDNA-binding
   Molecular functionGlycosidase
Hydrolase
Lyase
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processbase-excision repair

Inferred from direct assay PubMed 17611195. Source: UniProtKB

negative regulation of nuclease activity

Inferred from direct assay PubMed 17611195. Source: UniProtKB

nucleotide-excision repair

Inferred from electronic annotation. Source: InterPro

response to oxidative stress

Inferred from direct assay PubMed 17611195. Source: UniProtKB

   Cellular_componentchromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 17611195. Source: UniProtKB

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 17611195. Source: UniProtKB

   Molecular_functionDNA N-glycosylase activity

Inferred from electronic annotation. Source: Ensembl

DNA-(apurinic or apyrimidinic site) lyase activity

Inferred from electronic annotation. Source: UniProtKB-EC

damaged DNA binding

Inferred from electronic annotation. Source: InterPro

hydrolase activity, acting on glycosyl bonds

Inferred from direct assay PubMed 17611195. Source: UniProtKB

protein C-terminus binding

Inferred from physical interaction PubMed 17611195. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 390389Endonuclease 8-like 1
PRO_0000170905

Sites

Active site21Schiff-base intermediate with DNA Probable
Active site31Proton donor Probable
Active site541Proton donor; for beta-elimination activity Probable
Active site3391Proton donor; for delta-elimination activity Probable
Binding site1761DNA By similarity
Binding site3391DNA By similarity

Natural variations

Natural variant821S → C. Ref.3
Corresponds to variant rs5745905 [ dbSNP | Ensembl ].
VAR_020580
Natural variant831G → D. Ref.3
Corresponds to variant rs5745906 [ dbSNP | Ensembl ].
VAR_020581
Natural variant1361C → R. Ref.3
Corresponds to variant rs5745907 [ dbSNP | Ensembl ].
VAR_020582
Natural variant1591R → Q. Ref.13
VAR_065963
Natural variant1811E → K Found in a patient with nephrotic syndrome also carrying mutation P-159 in MYO1E. Ref.13
VAR_065964
Natural variant1821I → M.
Corresponds to variant rs7183491 [ dbSNP | Ensembl ].
VAR_020583
Natural variant2421K → R in RNA edited version.
VAR_065018
Natural variant2521D → N. Ref.3
Corresponds to variant rs5745926 [ dbSNP | Ensembl ].
VAR_020584

Experimental info

Mutagenesis21P → T: Loss of glycosylase and AP lyase activity. Ref.7 Ref.8
Mutagenesis21Missing: Loss of glycosylase activity. Ref.7 Ref.8
Mutagenesis31E → Q: Loss of glycosylase and AP lyase activity. Ref.7
Mutagenesis541K → L: Loss of glycosylase activity. Ref.9
Mutagenesis2771R → A: Strongly reduced glycosylase activity. Has little effect on AP lyase activity. Ref.12
Sequence conflict1471N → S in BAB15337. Ref.2

Secondary structure

................................................... 390
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96FI4 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: B2B058486C4EF835

FASTA39043,684
        10         20         30         40         50         60 
MPEGPELHLA SQFVNEACRA LVFGGCVEKS SVSRNPEVPF ESSAYRISAS ARGKELRLIL 

        70         80         90        100        110        120 
SPLPGAQPQQ EPLALVFRFG MSGSFQLVPR EELPRHAHLR FYTAPPGPRL ALCFVDIRRF 

       130        140        150        160        170        180 
GRWDLGGKWQ PGRGPCVLQE YQQFRENVLR NLADKAFDRP ICEALLDQRF FNGIGNYLRA 

       190        200        210        220        230        240 
EILYRLKIPP FEKARSVLEA LQQHRPSPEL TLSQKIRTKL QNPDLLELCH SVPKEVVQLG 

       250        260        270        280        290        300 
GKGYGSESGE EDFAAFRAWL RCYGMPGMSS LQDRHGRTIW FQGDPGPLAP KGRKSRKKKS 

       310        320        330        340        350        360 
KATQLSPEDR VEDALPPSKA PSRTRRAKRD LPKRTATQRP EGTSLQQDPE APTVPKKGRR 

       370        380        390 
KGRQAASGHC RPRKVKADIP SLEPEGTSAS 

« Hide

References

« Hide 'large scale' references
[1]"A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue."
Takao M., Kanno S., Kobayashi K., Zhang Q.-M., Yonei S., van der Horst G.T.J., Yasui A.
J. Biol. Chem. 277:42205-42213(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Testis.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]NIEHS SNPs program
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-82; ASP-83; ARG-136 AND ASN-252.
[4]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
Tissue: Lung.
[7]"A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII."
Bandaru V., Sunkara S., Wallace S.S., Bond J.P.
DNA Repair 1:517-529(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-2 AND GLU-3, FUNCTION.
[8]"Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA."
Hazra T.K., Izumi T., Boldogh I., Imhoff B., Kow Y.W., Jaruga P., Dizdaroglu M., Mitra S.
Proc. Natl. Acad. Sci. U.S.A. 99:3523-3528(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-2, FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[9]"Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2."
Dou H., Mitra S., Hazra T.K.
J. Biol. Chem. 278:49679-49684(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-54.
[10]"Human NEIL1 localizes with the centrosomes and condensed chromosomes during mitosis."
Hildrestrand G.A., Rolseth V., Bjoras M., Luna L.
DNA Repair 6:1425-1433(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1."
Yeo J., Goodman R.A., Schirle N.T., David S.S., Beal P.A.
Proc. Natl. Acad. Sci. U.S.A. 107:20715-20719(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: RNA EDITING OF POSITION 242.
[12]"The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity."
Doublie S., Bandaru V., Bond J.P., Wallace S.S.
Proc. Natl. Acad. Sci. U.S.A. 101:10284-10289(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-334, MUTAGENESIS OF ARG-277.
[13]"Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome."
Sanna-Cherchi S., Burgess K.E., Nees S.N., Caridi G., Weng P.L., Dagnino M., Bodria M., Carrea A., Allegretta M.A., Kim H.R., Perry B.J., Gigante M., Clark L.N., Kisselev S., Cusi D., Gesualdo L., Allegri L., Scolari F. expand/collapse author list , D'Agati V., Shapiro L.S., Pecoraro C., Palomero T., Ghiggeri G.M., Gharavi A.G.
Kidney Int. 80:389-396(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLN-159 AND LYS-181.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB079068 mRNA. Translation: BAC06476.1.
AK026055 mRNA. Translation: BAB15337.1.
AK128372 mRNA. No translation available.
AY257544 Genomic DNA. Translation: AAO74826.1.
AC068338 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99255.1.
CH471136 Genomic DNA. Translation: EAW99260.1.
BC010876 mRNA. Translation: AAH10876.1.
CCDSCCDS10278.1.
RefSeqNP_001243481.1. NM_001256552.1.
NP_078884.2. NM_024608.3.
XP_005254716.1. XM_005254659.2.
XP_006720743.1. XM_006720680.1.
XP_006720744.1. XM_006720681.1.
XP_006720745.1. XM_006720682.1.
UniGeneHs.512732.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TDHX-ray2.10A1-390[»]
4NRVX-ray2.60A2-290[»]
ProteinModelPortalQ96FI4.
SMRQ96FI4. Positions 2-290.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122787. 5 interactions.
STRING9606.ENSP00000347170.

PTM databases

PhosphoSiteQ96FI4.

Polymorphism databases

DMDM56404654.

Proteomic databases

PaxDbQ96FI4.
PRIDEQ96FI4.

Protocols and materials databases

DNASU79661.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355059; ENSP00000347170; ENSG00000140398.
ENST00000564784; ENSP00000457352; ENSG00000140398.
ENST00000569035; ENSP00000455730; ENSG00000140398.
GeneID79661.
KEGGhsa:79661.
UCSCuc002bad.4. human.

Organism-specific databases

CTD79661.
GeneCardsGC15P075639.
H-InvDBHIX0202149.
HGNCHGNC:18448. NEIL1.
HPAHPA054084.
MIM608844. gene.
neXtProtNX_Q96FI4.
PharmGKBPA38334.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75119.
HOGENOMHOG000067872.
HOVERGENHBG052592.
InParanoidQ96FI4.
KOK10567.
OMAHLASHFV.
PhylomeDBQ96FI4.
TreeFamTF333272.

Enzyme and pathway databases

BRENDA3.2.2.23. 2681.

Gene expression databases

ArrayExpressQ96FI4.
BgeeQ96FI4.
CleanExHS_NEIL1.
GenevestigatorQ96FI4.

Family and domain databases

InterProIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR015371. Endonuclease-VIII_DNA-bd.
IPR010979. Ribosomal_S13-like_H2TH.
[Graphical view]
PfamPF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
PF09292. Neil1-DNA_bind. 1 hit.
[Graphical view]
SMARTSM00898. Fapy_DNA_glyco. 1 hit.
[Graphical view]
SUPFAMSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
PROSITEPS51068. FPG_CAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96FI4.
GeneWikiNEIL1.
GenomeRNAi79661.
NextBio68852.
PROQ96FI4.
SOURCESearch...

Entry information

Entry nameNEIL1_HUMAN
AccessionPrimary (citable) accession number: Q96FI4
Secondary accession number(s): D3DW75 expand/collapse secondary AC list , Q6ZRA7, Q86XW7, Q9H6C3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 122 of the entry and version 3 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM