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Protein

Endonuclease 8-like 3

Gene

Neil3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.6 Publications

Catalytic activityi

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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2Schiff-base intermediate with DNA; via amino nitrogen1 Publication1
Sitei2Important for monofunctional glycosylase activityBy similarity1
Sitei82Required for glycosylase activityBy similarity1
Binding sitei193DNABy similarity1
Binding sitei272DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri248 – 282FPG-typePROSITE-ProRule annotationAdd BLAST35
Zinc fingeri318 – 347RanBP2-typePROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

  • bubble DNA binding Source: UniProtKB
  • damaged DNA binding Source: InterPro
  • DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
  • DNA N-glycosylase activity Source: UniProtKB
  • double-stranded DNA binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • base-excision repair Source: UniProtKB
  • nucleotide-excision repair Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase, Lyase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
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 namesi
Name:Neil3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2384588. Neil3.

Subcellular locationi

  • Nucleus 1 Publication

GO - Cellular componenti

  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCurated
ChainiPRO_00001709112 – 606Endonuclease 8-like 3Add BLAST605

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei451PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8K203.
PaxDbiQ8K203.
PeptideAtlasiQ8K203.
PRIDEiQ8K203.

PTM databases

iPTMnetiQ8K203.
PhosphoSitePlusiQ8K203.

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

Highly expressed in the developing brain at E12-E13 when neurogenesis starts. Expression decreases during later development and is undetectable in adult brain.2 Publications

Inductioni

By mitogen stimulation in splenocytes, and by hypoxic-ischemic injury in the striatum and hippocampus.2 Publications

Gene expression databases

BgeeiENSMUSG00000039396.
CleanExiMM_NEIL3.
ExpressionAtlasiQ8K203. baseline and differential.
GenevisibleiQ8K203. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000041909.

Structurei

Secondary structure

1606
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 17Combined sources14
Beta strandi23 – 28Combined sources6
Helixi30 – 34Combined sources5
Helixi64 – 68Combined sources5
Turni69 – 71Combined sources3
Beta strandi73 – 80Combined sources8
Beta strandi83 – 88Combined sources6
Beta strandi91 – 106Combined sources16
Beta strandi119 – 126Combined sources8
Beta strandi128 – 140Combined sources13
Helixi141 – 151Combined sources11
Helixi152 – 154Combined sources3
Helixi163 – 171Combined sources9
Beta strandi175 – 177Combined sources3
Helixi178 – 183Combined sources6
Turni185 – 187Combined sources3
Helixi193 – 203Combined sources11
Helixi211 – 213Combined sources3
Helixi216 – 239Combined sources24
Helixi243 – 246Combined sources4
Turni256 – 258Combined sources3
Beta strandi263 – 265Combined sources3
Beta strandi274 – 276Combined sources3
Turni278 – 280Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3W0FX-ray2.00A2-282[»]
ProteinModelPortaliQ8K203.
SMRiQ8K203.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

Sequence similaritiesi

Belongs to the FPG family.PROSITE-ProRule annotation
Contains 1 FPG-type zinc finger.PROSITE-ProRule annotation
Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri248 – 282FPG-typePROSITE-ProRule annotationAdd BLAST35
Zinc fingeri318 – 347RanBP2-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IETI. Eukaryota.
ENOG410ZE81. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000113754.
HOVERGENiHBG052594.
InParanoidiQ8K203.
KOiK10569.
OMAiCFFDSSV.
OrthoDBiEOG091G038I.
PhylomeDBiQ8K203.
TreeFamiTF331502.

Family and domain databases

InterProiIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR015887. DNA_glyclase_Znf_dom_DNA_BS.
IPR012319. FPG_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
IPR010666. Znf_GRF.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF06831. H2TH. 1 hit.
PF06839. zf-GRF. 2 hits.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTiSM01232. H2TH. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
SSF90209. SSF90209. 1 hit.
PROSITEiPS51068. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8K203-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVEGPGCTLN GEKIRARVLP GQAVTGVRGT ALQSLLGPAM SPAASLADVA
60 70 80 90 100
TSAAPMNAKD SGWKLLRLFN GYVYSGVETL GKELFMYFGP RALRIHFGMK
110 120 130 140 150
GSILINPREG ENRAGASPAL AVQLTRDLIC FYDSSVELRN SVESQQRVRV
160 170 180 190 200
MEELDICSPK FSFSRAESEV KKQGDRMLCD VLLDQRVLPG VGNIIKNEAL
210 220 230 240 250
FDSGLHPAVK VCQLSDKQAC HLVKMTRDFS ILFYRCCKAG SAISKHCKVY
260 270 280 290 300
KRPNCDQCHS KITVCRFGEN SRMTYFCPHC QKENPQCVQV CQLPTRNTEI
310 320 330 340 350
SWTPRGEDCF TDSVARKSEE QWSCVVCTLI NRPSAKACDA CLTTRPLDSV
360 370 380 390 400
LKNRENSIAF NNLVKYPCNN FENTHTEVKI NRKTAFGNTT LVLTDLSNKS
410 420 430 440 450
SALARKKRAN HTIDGESQMF LPTDIGFSDS QHPSKEGINY ITQPSNKVNI
460 470 480 490 500
SPTVCAQSKL FSSAHKKFKP AHTSATELKS YNSGLSNSEL QTNRTRGHHS
510 520 530 540 550
KSDGSPLCKM HHRRCVLRVV RKDGENKGRQ FYACSLPRGA QCGFFEWADL
560 570 580 590 600
SFPFCRHGKR SIMKTVLKIG PNNGKNFFVC PLEKKKQCNF FQWAENGPGM

EIVPGC
Length:606
Mass (Da):67,416
Last modified:October 1, 2002 - v1
Checksum:i941C38FA8538BAA8
GO
Isoform 2 (identifier: Q8K203-2) [UniParc]FASTAAdd to basket

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

Note: May be due to an intron retention.
Show »
Length:211
Mass (Da):22,840
Checksum:iE7643F8B173F69CE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti46L → P in strain: Czech II. 1 Publication1
Natural varianti90P → H in strain: Czech II. 1 Publication1
Natural varianti114A → G in strain: Czech II. 1 Publication1
Natural varianti150V → E in strain: Czech II. 1 Publication1
Natural varianti220C → R in strain: Czech II. 1 Publication1
Natural varianti256D → G in strain: Czech II. 1 Publication1
Natural varianti287C → R in strain: Czech II. 1 Publication1
Natural varianti325V → A in strain: Czech II. 1 Publication1
Natural varianti556R → K in strain: Czech II. 1 Publication1
Natural varianti585K → E in strain: Czech II. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012210212 – 606Missing in isoform 2. 1 PublicationAdd BLAST395

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS22305.1. [Q8K203-1]
RefSeqiNP_666320.1. NM_146208.2. [Q8K203-1]
UniGeneiMm.281749.

Genome annotation databases

EnsembliENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396. [Q8K203-1]
GeneIDi234258.
KEGGimmu:234258.
UCSCiuc009lsa.2. mouse. [Q8K203-1]
uc009lsb.2. mouse. [Q8K203-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS22305.1. [Q8K203-1]
RefSeqiNP_666320.1. NM_146208.2. [Q8K203-1]
UniGeneiMm.281749.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3W0FX-ray2.00A2-282[»]
ProteinModelPortaliQ8K203.
SMRiQ8K203.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000041909.

PTM databases

iPTMnetiQ8K203.
PhosphoSitePlusiQ8K203.

Proteomic databases

EPDiQ8K203.
PaxDbiQ8K203.
PeptideAtlasiQ8K203.
PRIDEiQ8K203.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396. [Q8K203-1]
GeneIDi234258.
KEGGimmu:234258.
UCSCiuc009lsa.2. mouse. [Q8K203-1]
uc009lsb.2. mouse. [Q8K203-2]

Organism-specific databases

CTDi55247.
MGIiMGI:2384588. Neil3.

Phylogenomic databases

eggNOGiENOG410IETI. Eukaryota.
ENOG410ZE81. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000113754.
HOVERGENiHBG052594.
InParanoidiQ8K203.
KOiK10569.
OMAiCFFDSSV.
OrthoDBiEOG091G038I.
PhylomeDBiQ8K203.
TreeFamiTF331502.

Miscellaneous databases

PROiQ8K203.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039396.
CleanExiMM_NEIL3.
ExpressionAtlasiQ8K203. baseline and differential.
GenevisibleiQ8K203. MM.

Family and domain databases

InterProiIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR015887. DNA_glyclase_Znf_dom_DNA_BS.
IPR012319. FPG_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
IPR010666. Znf_GRF.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF06831. H2TH. 1 hit.
PF06839. zf-GRF. 2 hits.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTiSM01232. H2TH. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
SSF90209. SSF90209. 1 hit.
PROSITEiPS51068. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiNEIL3_MOUSE
AccessioniPrimary (citable) accession number: Q8K203
Secondary accession number(s): Q4ADY6, Q8CD85, Q8R3P4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: October 1, 2002
Last modified: November 2, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.