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Protein

Endonuclease 8-like 3

Gene

NEIL3

Organism
Homo sapiens (Human)
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.4 Publications

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

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 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

  • base-excision repair Source: HGNC
  • nucleotide-excision repair Source: InterPro

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

Organism-specific databases

EuPathDBiHostDB:ENSG00000109674.3
HGNCiHGNC:24573 NEIL3
MIMi608934 gene
neXtProtiNX_Q8TAT5

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

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
ProteomicsDBi73916

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, 20 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

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
OMAiIHFGMKG
OrthoDBiEOG091G038I
PhylomeDBiQ8TAT5
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

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 → C1 PublicationCorresponds to variant dbSNP:rs34007209Ensembl.1
Natural variantiVAR_02580758N → NN1 Publication1
Natural variantiVAR_02580876V → M1 PublicationCorresponds to variant dbSNP:rs34112288Ensembl.1
Natural variantiVAR_020590117P → R2 PublicationsCorresponds to variant dbSNP:rs7689099Ensembl.1
Natural variantiVAR_025809172Q → H1 PublicationCorresponds to variant dbSNP:rs17064658Ensembl.1
Natural variantiVAR_025810286H → R1 PublicationCorresponds to variant dbSNP:rs34193982Ensembl.1
Natural variantiVAR_025811346I → V1 PublicationCorresponds to variant dbSNP:rs17064676Ensembl.1
Natural variantiVAR_020591443P → L4 PublicationsCorresponds to variant dbSNP:rs13112358Ensembl.1
Natural variantiVAR_025812471Q → H4 PublicationsCorresponds to variant dbSNP:rs13112390Ensembl.1
Natural variantiVAR_020592520G → R4 PublicationsCorresponds to variant dbSNP:rs1876268Ensembl.1
Natural variantiVAR_025813547A → S1 PublicationCorresponds to variant dbSNP:rs36005630Ensembl.1
Natural variantiVAR_025814556H → R1 PublicationCorresponds to variant dbSNP:rs35418725Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiNEIL3_HUMAN
AccessioniPrimary (citable) accession number: Q8TAT5
Secondary accession number(s): Q2PPJ3, Q8NG51, Q9NV95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: August 10, 2010
Last modified: June 20, 2018
This is version 134 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

Complete proteome, 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

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