Q8K203 (NEIL3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endonuclease 8-like 3
EC=3.2.2.-
EC=4.2.99.18

Alternative name(s):
DNA glycosylase FPG2
DNA glycosylase/AP lyase Neil3
Endonuclease VIII-like 3
Nei-like protein 3

Gene names

Name:

Neil3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	606 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	Reports about DNA glycosylase activity are contradictory. A number of references report finding no DNA glycosylase activity and the protein lacks a proline residue at the N-terminus which functions as an active site residue in other members of the FPG family. However, Ref.4 has demonstrated that the protein has both DNA glycosylase and AP lyase activities and the human ortholog has been shown to possess AP lyase activity. Prefers single-stranded DNA or partially single-stranded DNA structures such as bubble and fork structures to double-stranded DNA in vitro. Displays a broad recognition spectrum, preferring FapyA and FapyG followed by 5-OHU, 5-PHC and 5-OHMH and then Tg and 8-oxoA. No activity on 8-oxoG detected. Ref.4
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 Ref.1.
Tissue specificity	Expressed in testis, thymus, spleen and bone marrow. In young mice, expressed at higher levels in thymocytes than splenocytes. At E12, abundant in the subventricular zone (SVZ) of the lateral ventricles. At E17.5 and P0, expression is limited to distinct cells in the cortical SVZ, in cells of the secondary matrix, the dentate gyrus migratory route and the dentate gyrus. Ref.1 Ref.5 Ref.6
Developmental stage	Highly expressed in the developing brain at E12-E13 when neurogenesis starts. Expression decreases during later development and is undetectable in adult brain. Ref.5 Ref.6
Induction	By mitogen stimulation in splenocytes. Ref.1
Disruption phenotype	No effect on viability or fertility. Ref.1
Sequence similarities	Belongs to the FPG family. Contains 1 FPG-type zinc finger. Contains 1 RanBP2-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Glycosidase Hydrolase Lyase
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	base-excision repair Inferred from direct assay Ref.4. Source: UniProtKB nucleotide-excision repair Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	DNA N-glycosylase activity Inferred from direct assay Ref.4. Source: UniProtKB DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay Ref.4. Source: UniProtKB bubble DNA binding Inferred from direct assay Ref.4. Source: UniProtKB damaged DNA binding Inferred from electronic annotation. Source: InterPro double-stranded DNA binding Inferred from direct assay Ref.4. Source: UniProtKB single-stranded DNA binding Inferred from direct assay Ref.4. 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: Q8K203-1)

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: Q8K203-2)

The sequence of this isoform differs from the canonical sequence as follows:
     212-606: Missing.

Note: May be due to an intron retention.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 606

605

Endonuclease 8-like 3

PRO_0000170911

Regions

Zinc finger

248 – 282

35

FPG-type

Zinc finger

318 – 347

30

RanBP2-type

Sites

Active site

2

1

Schiff-base intermediate with DNA; via amino nitrogen Probable

Binding site

193

1

DNA By similarity

Binding site

272

1

DNA By similarity

Natural variations

Alternative sequence

212 – 606

395

Missing in isoform 2.

VSP_012210

Natural variant

46

1

L → P in strain: Czech II. Ref.3

Natural variant

90

1

P → H in strain: Czech II. Ref.3

Natural variant

114

1

A → G in strain: Czech II. Ref.3

Natural variant

150

1

V → E in strain: Czech II. Ref.3

Natural variant

220

1

C → R in strain: Czech II. Ref.3

Natural variant

256

1

D → G in strain: Czech II. Ref.3

Natural variant

287

1

C → R in strain: Czech II. Ref.3

Natural variant

325

1

V → A in strain: Czech II. Ref.3

Natural variant

556

1

R → K in strain: Czech II. Ref.3

Natural variant

585

1

K → E in strain: Czech II. Ref.3

Secondary structure

1

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606

Helix Strand Turn

Details...

Helix

4 – 17

14

Beta strand

23 – 28

6

Helix

30 – 34

5

Helix

64 – 68

5

Turn

69 – 71

3

Beta strand

73 – 80

8

Beta strand

83 – 88

6

Beta strand

91 – 106

16

Beta strand

119 – 126

8

Beta strand

128 – 140

13

Helix

141 – 151

11

Helix

152 – 154

3

Helix

163 – 171

9

Beta strand

175 – 177

3

Helix

178 – 183

6

Turn

185 – 187

3

Helix

193 – 203

11

Helix

211 – 213

3

Helix

216 – 239

24

Helix

243 – 246

4

Turn

256 – 258

3

Beta strand

263 – 265

3

Beta strand

274 – 276

3

Turn

278 – 280

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 941C38FA8538BAA8	FASTA	606	67,416
	10 20 30 40 50 60 MVEGPGCTLN GEKIRARVLP GQAVTGVRGT ALQSLLGPAM SPAASLADVA TSAAPMNAKD 70 80 90 100 110 120 SGWKLLRLFN GYVYSGVETL GKELFMYFGP RALRIHFGMK GSILINPREG ENRAGASPAL 130 140 150 160 170 180 AVQLTRDLIC FYDSSVELRN SVESQQRVRV MEELDICSPK FSFSRAESEV KKQGDRMLCD 190 200 210 220 230 240 VLLDQRVLPG VGNIIKNEAL FDSGLHPAVK VCQLSDKQAC HLVKMTRDFS ILFYRCCKAG 250 260 270 280 290 300 SAISKHCKVY KRPNCDQCHS KITVCRFGEN SRMTYFCPHC QKENPQCVQV CQLPTRNTEI 310 320 330 340 350 360 SWTPRGEDCF TDSVARKSEE QWSCVVCTLI NRPSAKACDA CLTTRPLDSV LKNRENSIAF 370 380 390 400 410 420 NNLVKYPCNN FENTHTEVKI NRKTAFGNTT LVLTDLSNKS SALARKKRAN HTIDGESQMF 430 440 450 460 470 480 LPTDIGFSDS QHPSKEGINY ITQPSNKVNI SPTVCAQSKL FSSAHKKFKP AHTSATELKS 490 500 510 520 530 540 YNSGLSNSEL QTNRTRGHHS KSDGSPLCKM HHRRCVLRVV RKDGENKGRQ FYACSLPRGA 550 560 570 580 590 600 QCGFFEWADL SFPFCRHGKR SIMKTVLKIG PNNGKNFFVC PLEKKKQCNF FQWAENGPGM EIVPGC
	Isoform 2 [UniParc]. Checksum: E7643F8B173F69CE	FASTA	211	22,840
	10 20 30 40 50 60 MVEGPGCTLN GEKIRARVLP GQAVTGVRGT ALQSLLGPAM SPAASLADVA TSAAPMNAKD 70 80 90 100 110 120 SGWKLLRLFN GYVYSGVETL GKELFMYFGP RALRIHFGMK GSILINPREG ENRAGASPAL 130 140 150 160 170 180 AVQLTRDLIC FYDSSVELRN SVESQQRVRV MEELDICSPK FSFSRAESEV KKQGDRMLCD 190 200 210 VLLDQRVLPG VGNIIKNEAL FDSGLHPAVK V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein." Torisu K., Tsuchimoto D., Ohnishi Y., Nakabeppu Y. J. Biochem. 138:763-772(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, DISRUPTION PHENOTYPE. Tissue: Splenocyte.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Thymus.
[3]	"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] (ISOFORM 1), VARIANTS PRO-46; HIS-90; GLY-114; GLU-150; ARG-220; GLY-256; ARG-287; ALA-325; LYS-556 AND GLU-585. Strain: Czech II and FVB/N. Tissue: Mammary tumor.
[4]	"The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo." Liu M., Bandaru V., Bond J.P., Jaruga P., Zhao X., Christov P.P., Burrows C.J., Rizzo C.J., Dizdaroglu M., Wallace S.S. Proc. Natl. Acad. Sci. U.S.A. 107:4925-4930(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, ACTIVE SITE.
[5]	"Expression patterns of Neil3 during embryonic brain development and neoplasia." Hildrestrand G.A., Neurauter C.G., Diep D.B., Castellanos C.G., Krauss S., Bjoras M., Luna L. BMC Neurosci. 10:45-45(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]	"Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant." Takao M., Oohata Y., Kitadokoro K., Kobayashi K., Iwai S., Yasui A., Yonei S., Zhang Q.M. Genes Cells 14:261-270(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB072931 mRNA. Translation: BAC22661.1.
AK031027 mRNA. Translation: BAC27219.1.
BC024921 mRNA. Translation: AAH24921.1.
BC034753 mRNA. Translation: AAH34753.1.

IPI

IPI00169796.
IPI00480517.

RefSeq

NP_666320.1. NM_146208.2.

UniGene

Mm.281749.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3W0F	X-ray	2.00	A	2-282	[»]

ProteinModelPortal

Q8K203.

SMR

Q8K203. Positions 71-285.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000041909.

PTM databases

PhosphoSite

Q8K203.

Proteomic databases

PRIDE

Q8K203.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396.

GeneID

234258.

KEGG

mmu:234258.

UCSC

uc009lsa.2. mouse.
uc009lsb.2. mouse.

Organism-specific databases

CTD

55247.

MGI

MGI:2384588. Neil3.

Phylogenomic databases

eggNOG

COG0266.

GeneTree

ENSGT00510000048146.

HOGENOM

HOG000113754.

HOVERGEN

HBG052594.

InParanoid

Q8K203.

KO

K10569.

OMA

TKDLICF.

OrthoDB

EOG48GW30.

Gene expression databases

ArrayExpress

Q8K203.

Bgee

Q8K203.

CleanEx

MM_NEIL3.

Genevestigator

Q8K203.

GermOnline

ENSMUSG00000039396. Mus musculus.

Family and domain databases

InterPro

IPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR015887. DNA_glyclase_Znf_dom_DNA_BS.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
IPR010666. Znf_GRF.
IPR001876. Znf_RanBP2.
[Graphical view]

Pfam

PF06831. H2TH. 1 hit.
PF06839. zf-GRF. 2 hits.
PF00641. zf-RanBP. 1 hit.
[Graphical view]

SMART

SM00547. ZnF_RBZ. 1 hit.
[Graphical view]

SUPFAM

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

PROSITE

PS51068. FPG_CAT. 1 hit.
PS01242. ZF_FPG_1. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NEIL3. mouse.

NextBio

382073.

SOURCE

Search...

Entry information

Entry name

NEIL3_MOUSE

Accession

Primary (citable) accession number: Q8K203
Secondary accession number(s): Q8CD85, Q8R3P4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program