Q96FI4 (NEIL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	390 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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	Cytoplasm › cytoskeleton › centrosome. 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 process	DNA damage DNA repair
Cellular component	Chromosome Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Polymorphism RNA editing
Ligand	DNA-binding
Molecular function	Glycosidase Hydrolase Lyase
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	base-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_component	chromosome 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_function	DNA N-glycosylase activity Inferred from electronic annotation. Source: Compara DNA-(apurinic or apyrimidinic site) lyase activity Inferred from electronic annotation. Source: EC damaged DNA binding Inferred from electronic annotation. Source: InterPro hydrolase activity, acting on glycosyl bonds Inferred from direct assay PubMed 17611195. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 390

389

Endonuclease 8-like 1

PRO_0000170905

Sites

Active site

2

1

Schiff-base intermediate with DNA Probable

Active site

3

1

Proton donor Probable

Active site

54

1

Proton donor; for beta-elimination activity Probable

Active site

339

1

Proton donor; for delta-elimination activity Probable

Binding site

176

1

DNA By similarity

Binding site

339

1

DNA By similarity

Natural variations

Natural variant

82

1

S → C. Ref.3
Corresponds to variant rs5745905 [ dbSNP | Ensembl ].

VAR_020580

Natural variant

83

1

G → D. Ref.3
Corresponds to variant rs5745906 [ dbSNP | Ensembl ].

VAR_020581

Natural variant

136

1

C → R. Ref.3
Corresponds to variant rs5745907 [ dbSNP | Ensembl ].

VAR_020582

Natural variant

159

1

R → Q. Ref.13

VAR_065963

Natural variant

181

1

E → K Found in a patient with nephrotic syndrome also carrying mutation P-159 in MYO1E. Ref.13

VAR_065964

Natural variant

182

1

I → M.
Corresponds to variant rs7183491 [ dbSNP | Ensembl ].

VAR_020583

Natural variant

242

1

K → R in RNA edited version.

VAR_065018

Natural variant

252

1

D → N. Ref.3
Corresponds to variant rs5745926 [ dbSNP | Ensembl ].

VAR_020584

Experimental info

Mutagenesis

2

1

P → T: Loss of glycosylase and AP lyase activity. Ref.7 Ref.8

Mutagenesis

2

1

Missing: Loss of glycosylase activity. Ref.7 Ref.8

Mutagenesis

3

1

E → Q: Loss of glycosylase and AP lyase activity. Ref.7

Mutagenesis

54

1

K → L: Loss of glycosylase activity. Ref.9

Mutagenesis

277

1

R → A: Strongly reduced glycosylase activity. Has little effect on AP lyase activity. Ref.12

Sequence conflict

147

1

N → S in BAB15337. Ref.2

Secondary structure

1

.

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390

Helix Strand Turn

Details...

Helix

4 – 18

15

Beta strand

23 – 26

4

Beta strand

41 – 52

12

Beta strand

55 – 62

8

Beta strand

73 – 78

6

Turn

80 – 82

3

Beta strand

84 – 89

6

Helix

90 – 92

3

Beta strand

97 – 103

7

Beta strand

105 – 108

4

Beta strand

110 – 115

6

Beta strand

122 – 127

6

Turn

137 – 139

3

Helix

141 – 150

10

Turn

151 – 153

3

Helix

155 – 158

4

Helix

161 – 164

4

Turn

168 – 170

3

Helix

176 – 186

11

Helix

194 – 198

5

Helix

199 – 201

3

Helix

212 – 218

7

Turn

219 – 221

3

Helix

225 – 240

16

Helix

249 – 259

11

Beta strand

269 – 272

4

Beta strand

278 – 283

6

Sequences

	Sequence		Length	Mass (Da)
	Q96FI4 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B2B058486C4EF835	FASTA	390	43,684
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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.

IPI

IPI00746550.

RefSeq

NP_001243481.1. NM_001256552.1.
NP_078884.2. NM_024608.3.

UniGene

Hs.512732.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TDH	X-ray	2.10	A	1-390	[»]

ProteinModelPortal

Q96FI4.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000347170.

PTM databases

PhosphoSite

Q96FI4.

Polymorphism databases

DMDM

56404654.

Proteomic databases

PaxDb

Q96FI4.

PRIDE

Q96FI4.

Protocols and materials databases

DNASU

79661.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355059; ENSP00000347170; ENSG00000140398.
ENST00000564784; ENSP00000457352; ENSG00000140398.
ENST00000569035; ENSP00000455730; ENSG00000140398.

GeneID

79661.

KEGG

hsa:79661.

UCSC

uc002bad.3. human.

Organism-specific databases

CTD

79661.

GeneCards

GC15P075639.

H-InvDB

HIX0202149.

HGNC

HGNC:18448. NEIL1.

HPA

HPA054084.

MIM

608844. gene.

neXtProt

NX_Q96FI4.

PharmGKB

PA38334.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG75119.

HOGENOM

HOG000067872.

HOVERGEN

HBG052592.

InParanoid

Q96FI4.

KO

K10567.

OMA

GTSLQQD.

OrthoDB

EOG479F7D.

PhylomeDB

Q96FI4.

Enzyme and pathway databases

BRENDA

3.2.2.23. 2681.

Gene expression databases

ArrayExpress

Q96FI4.

Bgee

Q96FI4.

CleanEx

HS_NEIL1.

Genevestigator

Q96FI4.

GermOnline

ENSG00000140398. Homo sapiens.

Family and domain databases

InterPro

IPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR015371. Endonuclease-VIII_DNA-bd.
IPR010979. Ribosomal_S13-like_H2TH.
[Graphical view]

Pfam

PF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
PF09292. Neil1-DNA_bind. 1 hit.
[Graphical view]

SMART

SM00898. Fapy_DNA_glyco. 1 hit.
[Graphical view]

SUPFAM

SSF81624. Form_DNAglyc_cat. 1 hit.
SSF46946. Ribosomal_H2TH. 1 hit.

PROSITE

PS51068. FPG_CAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96FI4.

GenomeRNAi

79661.

NextBio

68852.

SOURCE

Search...

Entry information

Entry name

NEIL1_HUMAN

Accession

Primary (citable) accession number: Q96FI4
Secondary accession number(s): D3DW75 , Q6ZRA7, Q86XW7, Q9H6C3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 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.