Reviewed, UniProtKB/Swiss-Prot Q96FI4 (NEIL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Endonuclease VIII-like 1
      Short name=Nei-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
    NEH1
    FPG1

Gene names

Name:

NEIL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.5 Ref.6 Ref.7
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	Nucleus.
Tissue specificity	Ubiquitous. Ref.6
Induction	Up-regulated during S-phase. Ref.6
Sequence similarities	Belongs to the FPG family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Glycosidase Hydrolase Lyase
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	base-excision repair Inferred from direct assay. Source: UniProtKB negative regulation of nuclease activity Inferred from direct assay. Source: UniProtKB nucleotide-excision repair Inferred from electronic annotation. Source: InterPro response to oxidative stress Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	DNA-(apurinic or apyrimidinic site) lyase activity Inferred from electronic annotation. Source: EC damaged DNA binding Inferred from electronic annotation. Source: InterPro protein C-terminus binding Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96FI4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96FI4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     75-139: LVFRFGMSGS...QPGRGPCVLQ → PRGAATPCPP...QGECATKPSG
     140-390: Missing.

Note: No experimental confirmation available.

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 VIII-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

Alternative sequence

75 – 139

65

LVFRF…PCVLQ → PRGAATPCPPALLHGPAWPP ARPMFRGHPPVRPLGPWGKV AAGPRALCLAGVPAVQGECA TKPSG in isoform 2.

VSP_012205

Alternative sequence

140 – 390

251

Missing in isoform 2.

VSP_012206

Natural variant

82

1

S → C in dnSNP:5745905. Ref.3

VAR_020580

Natural variant

83

1

G → D in dnSNP:5745906. Ref.3

VAR_020581

Natural variant

136

1

C → R in dnSNP:5745907. Ref.3

VAR_020582

Natural variant

182

1

I → M in dnSNP:7183491.

VAR_020583

Natural variant

252

1

D → N: dbSNP rs5745926. Ref.3

VAR_020584

Experimental info

Mutagenesis

2

1

P → T: Loss of glycosylase and AP lyase activity. Ref.5 Ref.6

Mutagenesis

2

1

Missing: Loss of glycosylase activity. Ref.5 Ref.6

Mutagenesis

3

1

E → Q: Loss of glycosylase and AP lyase activity. Ref.5

Mutagenesis

54

1

K → L: Loss of glycosylase activity. Ref.7

Mutagenesis

277

1

R → A: Strongly reduced glycosylase activity. Has little effect on AP lyase activity. Ref.8

Sequence conflict

147

1

N → S in BAB15337. Ref.2

Sequence conflict

242

1

K → R in BAC06476. Ref.1

Sequence conflict

242

1

K → R in BAB15337. Ref.2

Sequence conflict

242

1

K → R in AAH10876. Ref.4

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)
	Isoform 1 [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
	Isoform 2. Checksum: A5F4799A7C37471D	FASTA	139	14,483
	10 20 30 40 50 60 MPEGPELHLA SQFVNEACRA LVFGGCVEKS SVSRNPEVPF ESSAYRISAS ARGKELRLIL 70 80 90 100 110 120 SPLPGAQPQQ EPLAPRGAAT PCPPALLHGP AWPPARPMFR GHPPVRPLGP WGKVAAGPRA 130 LCLAGVPAVQ GECATKPSG

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: 12200441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[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]	"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] (ISOFORM 1). Tissue: Lung.
[5]	"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: 12509226] [Abstract] Cited for: MUTAGENESIS OF PRO-2 AND GLU-3, FUNCTION.
[6]	"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: 11904416] [Abstract] Cited for: MUTAGENESIS OF PRO-2, FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[7]	"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: 14522990] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-54.
[8]	"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: 15232006] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-334, MUTAGENESIS OF ARG-277.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB079068 mRNA. Translation: BAC06476.1.
AK026055 mRNA. Translation: BAB15337.1.
AK128372 mRNA. No translation available.
AY257544 Genomic DNA. Translation: AAO74826.1.
BC010876 mRNA. Translation: AAH10876.1.

IPI

IPI00305213.
IPI00746550.

RefSeq

NP_078884.2.

UniGene

Hs.512732

3D structure databases

PDBPDBe

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

ModBase

Search...

PTM databases

PhosphoSite

Q96FI4.

Proteomic databases

PRIDE

Q96FI4.

Genome annotation databases

Ensembl

ENSG00000140398. Homo sapiens. [Contig view]

GeneID

79661.

KEGG

hsa:79661.

Organism-specific databases

GeneCards

GC15P073426.

H-InvDB

HIX0012440.

HGNC

HGNC:18448. NEIL1.

MIM

608844. gene.

PharmGKB

PA38334.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96FI4.

HOVERGEN

Q96FI4.

OMA

Q96FI4. WFQGDPG.

Enzyme and pathway databases

BRENDA

3.2.2.23. 247.
4.2.99.18. 247.

Gene expression databases

Bgee

Q96FI4.

CleanEx

HS_NEIL1.

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.
[Graphical view]

Pfam

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

ProDom

PD003680. Fapy_DNA_glyco. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS51068. FPG_CAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

68852.

SOURCE

Search...

Entry information

Entry name

NEIL1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 74 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)