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Q8K203 (NEIL3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length606 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair. Ref.5 Ref.6 Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity

Removes damaged bases from DNA, leaving an abasic site. Ref.6 Ref.9 Ref.11 Ref.12

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. Ref.6 Ref.9 Ref.11 Ref.12

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.7 Ref.8 Ref.11

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.7 Ref.8

Induction

By mitogen stimulation in splenocytes, and by hypoxic-ischemic injury in the striatum and hippocampus. Ref.1 Ref.9

Domain

The N-terminal region (2-282) contains the glycosylase and lyase activities. Ref.5

Disruption phenotype

Perinatal mice show reduced regeneration of neural tissue following ischemic brain damage (stroke), associated with fewer activated microglia and impaired neural stem cell proliferation. Aged mice show deficits in learning and memory, decreased anxiety-like behavior, and changes in hippocampal synapse composition. Otherwise viable and fertile. Ref.1 Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the FPG family.

Contains 1 FPG-type zinc finger.

Contains 1 RanBP2-type zinc finger.

Caution

Was originally thought to be inactive as a glycosylase, but recent reports (PMID:22569481, PMID:20185759) demonstrate that cleavage of the initiator methionine is essential for catalytic activity.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Probable
Chain2 – 606605Endonuclease 8-like 3
PRO_0000170911

Regions

Zinc finger248 – 28235FPG-type
Zinc finger318 – 34730RanBP2-type

Sites

Active site21Schiff-base intermediate with DNA; via amino nitrogen Probable
Binding site1931DNA By similarity
Binding site2721DNA By similarity
Site21Important for monofunctional glycosylase activity By similarity
Site821Required for glycosylase activity By similarity

Natural variations

Alternative sequence212 – 606395Missing in isoform 2.
VSP_012210
Natural variant461L → P in strain: Czech II. Ref.3
Natural variant901P → H in strain: Czech II. Ref.3
Natural variant1141A → G in strain: Czech II. Ref.3
Natural variant1501V → E in strain: Czech II. Ref.3
Natural variant2201C → R in strain: Czech II. Ref.3
Natural variant2561D → G in strain: Czech II. Ref.3
Natural variant2871C → R in strain: Czech II. Ref.3
Natural variant3251V → A in strain: Czech II. Ref.3
Natural variant5561R → K in strain: Czech II. Ref.3
Natural variant5851K → E in strain: Czech II. Ref.3

Secondary structure

............................................. 606
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 941C38FA8538BAA8

FASTA60667,416
        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 

« Hide

Isoform 2 [UniParc].

Checksum: E7643F8B173F69CE
Show »

FASTA21122,840

References

« Hide '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. expand/collapse author list , 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]"Molecular cloning and chracterization of mouse DNA glycosylase gene, nei like 3 (Neil3); its regulated expression in lymphoid organs."
Torisu K., Tsuchimoto D., Ohnishi Y., Nakabeppu Y.
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
Strain: 129/SvJ.
[5]"Expression and purification of active mouse and human NEIL3 proteins."
Liu M., Bandaru V., Holmes A., Averill A.M., Cannan W., Wallace S.S.
Protein Expr. Purif. 84:130-139(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A GLYCOSYLASE/LYASE, CHARACTERIZATION OF N-TERMINAL DOMAIN, PROBABLE CLEAVAGE OF INITIATOR METHIONINE.
[6]"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: FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE.
[7]"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.
[8]"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.
[9]"Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia."
Sejersted Y., Hildrestrand G.A., Kunke D., Rolseth V., Krokeide S.Z., Neurauter C.G., Suganthan R., Atneosen-Asegg M., Fleming A.M., Saugstad O.D., Burrows C.J., Luna L., Bjoras M.
Proc. Natl. Acad. Sci. U.S.A. 108:18802-18807(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INDUCTION, DISRUPTION PHENOTYPE.
[10]"Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells."
Regnell C.E., Hildrestrand G.A., Sejersted Y., Medin T., Moldestad O., Rolseth V., Krokeide S.Z., Suganthan R., Luna L., Bjoras M., Bergersen L.H.
Cell Rep. 2:503-510(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]"Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress."
Rolseth V., Krokeide S.Z., Kunke D., Neurauter C.G., Suganthan R., Sejersted Y., Hildrestrand G.A., Bjoras M., Luna L.
Biochim. Biophys. Acta 1833:1157-1164(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[12]"Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNA."
Liu M., Imamura K., Averill A.M., Wallace S.S., Doublie S.
Structure 21:247-256(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-282 IN COMPLEX WITH ZINC, FUNCTION, CATALYTIC ACTIVITY.
+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.
AB202125 Genomic DNA. Translation: BAE16548.1.
RefSeqNP_666320.1. NM_146208.2.
UniGeneMm.281749.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3W0FX-ray2.00A2-282[»]
ProteinModelPortalQ8K203.
SMRQ8K203. Positions 2-282, 319-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000041909.

PTM databases

PhosphoSiteQ8K203.

Proteomic databases

PRIDEQ8K203.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396. [Q8K203-1]
GeneID234258.
KEGGmmu:234258.
UCSCuc009lsa.2. mouse. [Q8K203-1]
uc009lsb.2. mouse. [Q8K203-2]

Organism-specific databases

CTD55247.
MGIMGI:2384588. Neil3.

Phylogenomic databases

eggNOGCOG0266.
GeneTreeENSGT00730000110955.
HOGENOMHOG000113754.
HOVERGENHBG052594.
InParanoidQ8K203.
KOK10569.
OMAICFFDSS.
OrthoDBEOG7W153D.
PhylomeDBQ8K203.
TreeFamTF331502.

Gene expression databases

ArrayExpressQ8K203.
BgeeQ8K203.
CleanExMM_NEIL3.
GenevestigatorQ8K203.

Family and domain databases

InterProIPR015886. 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]
PfamPF06831. H2TH. 1 hit.
PF06839. zf-GRF. 2 hits.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
PROSITEPS51068. 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]
ProtoNetSearch...

Other

ChiTaRSNEIL3. mouse.
NextBio382073.
PROQ8K203.
SOURCESearch...

Entry information

Entry nameNEIL3_MOUSE
AccessionPrimary (citable) accession number: Q8K203
Secondary accession number(s): Q4ADY6, Q8CD85, Q8R3P4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot