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Protein

Endonuclease 8-like 3

Gene

NEIL3

Organism
Homo sapiens (Human)
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.4 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 nitrogenPROSITE-ProRule annotation1
Sitei2Important for monofunctional glycosylase activity1
Sitei81Required for glycosylase and lyase activities1
Binding sitei192DNABy similarity1
Binding sitei271DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri247 – 281FPG-typePROSITE-ProRule annotationAdd BLAST35
Zinc fingeri317 – 346RanBP2-typePROSITE-ProRule annotationAdd BLAST30

GO - Molecular functioni

GO - Biological processi

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:24573. NEIL3.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2V → P: No effect on AP lyase activity. Impairs monofunctional glycosylase activity. 2 Publications1
Mutagenesisi3E → A: No effect on AP lyase activity. 1 Publication1
Mutagenesisi81K → A: Loss of glycosylase and lyase activities. 1 Publication1
Mutagenesisi276C → S: Abolishes AP lyase activity. 1 Publication1
Mutagenesisi279C → S: Abolishes AP lyase activity. 1 Publication1

Organism-specific databases

DisGeNETi55247.
OpenTargetsiENSG00000109674.
PharmGKBiPA134889634.

Polymorphism and mutation databases

BioMutaiNEIL3.
DMDMi302393810.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCurated
ChainiPRO_00001709102 – 605Endonuclease 8-like 3Add BLAST604

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei450PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8TAT5.
MaxQBiQ8TAT5.
PaxDbiQ8TAT5.
PeptideAtlasiQ8TAT5.
PRIDEiQ8TAT5.

PTM databases

iPTMnetiQ8TAT5.
PhosphoSitePlusiQ8TAT5.

Expressioni

Tissue specificityi

Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts.4 Publications

Developmental stagei

Up-regulated during early S phase of the cell cycle, and sustained through G/M phase. Low expression levels in quiescent cells.1 Publication

Gene expression databases

BgeeiENSG00000109674.
CleanExiHS_NEIL3.
ExpressionAtlasiQ8TAT5. baseline and differential.
GenevisibleiQ8TAT5. HS.

Organism-specific databases

HPAiHPA065761.

Interactioni

Protein-protein interaction databases

BioGridi120538. 19 interactors.
IntActiQ8TAT5. 19 interactors.
STRINGi9606.ENSP00000264596.

Structurei

3D structure databases

ProteinModelPortaliQ8TAT5.
SMRiQ8TAT5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The N-terminal region (2-281) contains the glycosylase and lyase activities.By similarity

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 fingeri247 – 281FPG-typePROSITE-ProRule annotationAdd BLAST35
Zinc fingeri317 – 346RanBP2-typePROSITE-ProRule annotationAdd BLAST30

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IETI. Eukaryota.
ENOG410ZE81. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000113754.
HOVERGENiHBG052594.
InParanoidiQ8TAT5.
KOiK10569.
OMAiCFFDSSV.
OrthoDBiEOG091G038I.
PhylomeDBiQ8TAT5.
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]

Sequencei

Sequence statusi: Complete.

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

Q8TAT5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVEGPGCTLN GEKIRARVLP GQAVTGVRGS ALRSLQGRAL RLAASTVVVS
60 70 80 90 100
PQAAALNNDS SQNVLSLFNG YVYSGVETLG KELFMYFGPK ALRIHFGMKG
110 120 130 140 150
FIMINPLEYK YKNGASPVLE VQLTKDLICF FDSSVELRNS MESQQRIRMM
160 170 180 190 200
KELDVCSPEF SFLRAESEVK KQKGRMLGDV LMDQNVLPGV GNIIKNEALF
210 220 230 240 250
DSGLHPAVKV CQLTDEQIHH LMKMIRDFSI LFYRCRKAGL ALSKHYKVYK
260 270 280 290 300
RPNCGQCHCR ITVCRFGDNN RMTYFCPHCQ KENPQHVDIC KLPTRNTIIS
310 320 330 340 350
WTSSRVDHVM DSVARKSEEH WTCVVCTLIN KPSSKACDAC LTSRPIDSVL
360 370 380 390 400
KSEENSTVFS HLMKYPCNTF GKPHTEVKIN RKTAFGTTTL VLTDFSNKSS
410 420 430 440 450
TLERKTKQNQ ILDEEFQNSP PASVCLNDIQ HPSKKTTNDI TQPSSKVNIS
460 470 480 490 500
PTISSESKLF SPAHKKPKTA QYSSPELKSC NPGYSNSELQ INMTDGPRTL
510 520 530 540 550
NPDSPRCSKH NRLCILRVVG KDGENKGRQF YACPLPREAQ CGFFEWADLS
560 570 580 590 600
FPFCNHGKRS TMKTVLKIGP NNGKNFFVCP LGKEKQCNFF QWAENGPGIK

IIPGC
Length:605
Mass (Da):67,769
Last modified:August 10, 2010 - v3
Checksum:i528B17873ABC9D89
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35L → P in BAA91860 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02580638R → C.1 PublicationCorresponds to variant rs34007209dbSNPEnsembl.1
Natural variantiVAR_02580758N → NN.1 Publication1
Natural variantiVAR_02580876V → M.1 PublicationCorresponds to variant rs34112288dbSNPEnsembl.1
Natural variantiVAR_020590117P → R.2 PublicationsCorresponds to variant rs7689099dbSNPEnsembl.1
Natural variantiVAR_025809172Q → H.1 PublicationCorresponds to variant rs17064658dbSNPEnsembl.1
Natural variantiVAR_025810286H → R.1 PublicationCorresponds to variant rs34193982dbSNPEnsembl.1
Natural variantiVAR_025811346I → V.1 PublicationCorresponds to variant rs17064676dbSNPEnsembl.1
Natural variantiVAR_020591443P → L.4 PublicationsCorresponds to variant rs13112358dbSNPEnsembl.1
Natural variantiVAR_025812471Q → H.4 PublicationsCorresponds to variant rs13112390dbSNPEnsembl.1
Natural variantiVAR_020592520G → R.4 PublicationsCorresponds to variant rs1876268dbSNPEnsembl.1
Natural variantiVAR_025813547A → S.1 PublicationCorresponds to variant rs36005630dbSNPEnsembl.1
Natural variantiVAR_025814556H → R.1 PublicationCorresponds to variant rs35418725dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079071 mRNA. Translation: BAC06479.1.
AK001720 mRNA. Translation: BAA91860.1.
DQ310721 Genomic DNA. Translation: ABC40719.1.
AC027627 Genomic DNA. No translation available.
BC025954 mRNA. Translation: AAH25954.1.
CCDSiCCDS3828.1.
RefSeqiNP_060718.2. NM_018248.2.
UniGeneiHs.405467.

Genome annotation databases

EnsembliENST00000264596; ENSP00000264596; ENSG00000109674.
GeneIDi55247.
KEGGihsa:55247.
UCSCiuc003iut.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079071 mRNA. Translation: BAC06479.1.
AK001720 mRNA. Translation: BAA91860.1.
DQ310721 Genomic DNA. Translation: ABC40719.1.
AC027627 Genomic DNA. No translation available.
BC025954 mRNA. Translation: AAH25954.1.
CCDSiCCDS3828.1.
RefSeqiNP_060718.2. NM_018248.2.
UniGeneiHs.405467.

3D structure databases

ProteinModelPortaliQ8TAT5.
SMRiQ8TAT5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120538. 19 interactors.
IntActiQ8TAT5. 19 interactors.
STRINGi9606.ENSP00000264596.

PTM databases

iPTMnetiQ8TAT5.
PhosphoSitePlusiQ8TAT5.

Polymorphism and mutation databases

BioMutaiNEIL3.
DMDMi302393810.

Proteomic databases

EPDiQ8TAT5.
MaxQBiQ8TAT5.
PaxDbiQ8TAT5.
PeptideAtlasiQ8TAT5.
PRIDEiQ8TAT5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264596; ENSP00000264596; ENSG00000109674.
GeneIDi55247.
KEGGihsa:55247.
UCSCiuc003iut.3. human.

Organism-specific databases

CTDi55247.
DisGeNETi55247.
GeneCardsiNEIL3.
HGNCiHGNC:24573. NEIL3.
HPAiHPA065761.
MIMi608934. gene.
neXtProtiNX_Q8TAT5.
OpenTargetsiENSG00000109674.
PharmGKBiPA134889634.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IETI. Eukaryota.
ENOG410ZE81. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000113754.
HOVERGENiHBG052594.
InParanoidiQ8TAT5.
KOiK10569.
OMAiCFFDSSV.
OrthoDBiEOG091G038I.
PhylomeDBiQ8TAT5.
TreeFamiTF331502.

Miscellaneous databases

GeneWikiiNEIL3_(gene).
GenomeRNAii55247.
PROiQ8TAT5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109674.
CleanExiHS_NEIL3.
ExpressionAtlasiQ8TAT5. baseline and differential.
GenevisibleiQ8TAT5. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q8TAT5
Secondary accession number(s): Q2PPJ3, Q8NG51, Q9NV95
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: August 10, 2010
Last modified: November 2, 2016
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was originally thought to be inactive as a glycosylase (PMID:12200441,PMID:19121397), but recent reports (PMID:22569481, PMID:20185759) demonstrate that cleavage of the initiator methionine is essential for catalytic activity.Curated

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.