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Protein

Endonuclease 8-like 3

Gene

Neil3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

Catalytic activityi

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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Glycosidase, Hydrolase, Lyase, Multifunctional enzyme
Biological processDNA damage, DNA repair
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2384588 Neil3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 165 organ(s), highest expression level in bone marrow
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

3D structure databases

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

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
OMAiELDVCSP
OrthoDBiEOG091G038I
PhylomeDBiQ8K203
TreeFamiTF331502

Family and domain databases

Gene3Di3.20.190.10, 1 hit
InterProiView protein in InterPro
IPR015886 DNA_glyclase/AP_lyase_DNA-bd
IPR015887 DNA_glyclase_Znf_dom_DNA_BS
IPR012319 FPG_cat
IPR035937 MutM-like_N-ter
IPR010979 Ribosomal_S13-like_H2TH
IPR000214 Znf_DNA_glyclase/AP_lyase
IPR010666 Znf_GRF
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PfamiView protein in Pfam
PF06831 H2TH, 1 hit
PF06839 zf-GRF, 2 hits
PF00641 zf-RanBP, 1 hit
SMARTiView protein in SMART
SM01232 H2TH, 1 hit
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF46946 SSF46946, 1 hit
SSF81624 SSF81624, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in 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

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z1T7D3Z1T7_MOUSE
Endonuclease 8-like 3
Neil3
49Annotation score:

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

Similar proteinsi

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
OMAiELDVCSP
OrthoDBiEOG091G038I
PhylomeDBiQ8K203
TreeFamiTF331502

Miscellaneous databases

ChiTaRSiNeil3 mouse
PROiPR:Q8K203
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039396 Expressed in 165 organ(s), highest expression level in bone marrow
CleanExiMM_NEIL3
ExpressionAtlasiQ8K203 baseline and differential
GenevisibleiQ8K203 MM

Family and domain databases

Gene3Di3.20.190.10, 1 hit
InterProiView protein in InterPro
IPR015886 DNA_glyclase/AP_lyase_DNA-bd
IPR015887 DNA_glyclase_Znf_dom_DNA_BS
IPR012319 FPG_cat
IPR035937 MutM-like_N-ter
IPR010979 Ribosomal_S13-like_H2TH
IPR000214 Znf_DNA_glyclase/AP_lyase
IPR010666 Znf_GRF
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PfamiView protein in Pfam
PF06831 H2TH, 1 hit
PF06839 zf-GRF, 2 hits
PF00641 zf-RanBP, 1 hit
SMARTiView protein in SMART
SM01232 H2TH, 1 hit
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF46946 SSF46946, 1 hit
SSF81624 SSF81624, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in 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
ProtoNetiSearch...

Entry informationi

Entry nameiNEIL3_MOUSE
AccessioniPrimary (citable) accession number: Q8K203
Secondary accession number(s): Q4ADY6, Q8CD85, Q8R3P4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: October 1, 2002
Last modified: November 7, 2018
This is version 126 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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