Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Endonuclease 8-like 2

Gene

NEIL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Has DNA glycosylase activity towards 5-hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched double-stranded DNA (DNA bubbles). Has low or no DNA glycosylase activity towards thymine glycol, 2-hydroxyadenine, hypoxanthine and 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.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

Enzyme regulationi

Acetylation of Lys-50 leads to loss of DNA nicking activity. Acetylation of Lys-154 has no effect.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2Schiff-base intermediate with DNACurated1
Active sitei3Proton donorCurated1
Active sitei50Proton donor; for beta-elimination activityCurated1
Binding sitei231DNABy similarity1
Active sitei310Proton donor; for delta-elimination activityCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri284 – 320FPG-typePROSITE-ProRule annotationAdd BLAST37

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

Enzyme and pathway databases

BioCyciZFISH:HS07973-MONOMER.
BRENDAi3.2.2.23. 2681.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-5649702. APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Endonuclease 8-like 2 (EC:3.2.2.-, EC:4.2.99.18)
Alternative name(s):
DNA glycosylase/AP lyase Neil2
DNA-(apurinic or apyrimidinic site) lyase Neil2
Endonuclease VIII-like 2
Nei homolog 2
Short name:
NEH2
Nei-like protein 2
Gene namesi
Name:NEIL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:18956. NEIL2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi50K → R: Loss of glycosylase and AP lyase activity. 2 Publications1
Mutagenesisi154K → R: No effect on glycosylase and AP lyase activity. 1 Publication1
Mutagenesisi291C → S: Loss of glycosylase and AP lyase activity. 1 Publication1
Mutagenesisi295H → A: Loss of glycosylase and AP lyase activity. 1 Publication1
Mutagenesisi310R → Q: Strongly reduces strand AP lyase activity. 1 Publication1
Mutagenesisi315C → S: Loss of glycosylase and AP lyase activity. 1 Publication1
Mutagenesisi318C → S: Loss of glycosylase and AP lyase activity. 1 Publication1

Organism-specific databases

DisGeNETi252969.
OpenTargetsiENSG00000154328.
PharmGKBiPA38769.

Polymorphism and mutation databases

BioMutaiNEIL2.
DMDMi56404653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001709082 – 332Endonuclease 8-like 2Add BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50N6-acetyllysine1 Publication1
Modified residuei68PhosphoserineCombined sources1
Modified residuei154N6-acetyllysine1 Publication1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ969S2.
PaxDbiQ969S2.
PeptideAtlasiQ969S2.
PRIDEiQ969S2.

PTM databases

iPTMnetiQ969S2.
PhosphoSitePlusiQ969S2.

Expressioni

Tissue specificityi

Detected in testis, skeletal muscle, heart, brain, placenta, lung, pancreas, kidney and liver.1 Publication

Gene expression databases

BgeeiENSG00000154328.
CleanExiHS_NEIL2.
ExpressionAtlasiQ969S2. baseline and differential.
GenevisibleiQ969S2. HS.

Organism-specific databases

HPAiCAB017713.

Interactioni

Subunit structurei

Binds EP300.

Binary interactionsi

WithEntry#Exp.IntActNotes
MEOX1P502215EBI-10281234,EBI-2864512
RELQ048643EBI-10281234,EBI-307352
TRIM27P143735EBI-10281234,EBI-719493

Protein-protein interaction databases

BioGridi128946. 6 interactors.
IntActiQ969S2. 7 interactors.
MINTiMINT-4720021.
STRINGi9606.ENSP00000284503.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VZPmodel-A192-319[»]
ProteinModelPortaliQ969S2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The zinc-finger domain is important for DNA binding.

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri284 – 320FPG-typePROSITE-ProRule annotationAdd BLAST37

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJ89. Eukaryota.
ENOG4112BNS. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000069913.
HOVERGENiHBG082014.
InParanoidiQ969S2.
KOiK10568.
OMAiFLVFYNC.
OrthoDBiEOG091G0G2K.
PhylomeDBiQ969S2.
TreeFamiTF331502.

Family and domain databases

InterProiIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. FPG_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
[Graphical view]
PfamiPF06831. H2TH. 1 hit.
[Graphical view]
SMARTiSM01232. H2TH. 1 hit.
[Graphical view]
SUPFAMiSSF46946. SSF46946. 1 hit.
PROSITEiPS51068. FPG_CAT. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969S2-1) [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
MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVHGK
60 70 80 90 100
KLFLRFDLDE EMGPPGSSPT PEPPQKEVQK EGAADPKQVG EPSGQKTLDG
110 120 130 140 150
SSRSAELVPQ GEDDSEYLER DAPAGDAGRW LRVSFGLFGS VWVNDFSRAK
160 170 180 190 200
KANKRGDWRD PSPRLVLHFG GGGFLAFYNC QLSWSSSPVV TPTCDILSEK
210 220 230 240 250
FHRGQALEAL GQAQPVCYTL LDQRYFSGLG NIIKNEALYR AGIHPLSLGS
260 270 280 290 300
VLSASRREVL VDHVVEFSTA WLQGKFQGRP QHTQVYQKEQ CPAGHQVMKE
310 320 330
AFGPEDGLQR LTWWCPQCQP QLSEEPEQCQ FS
Length:332
Mass (Da):36,826
Last modified:January 23, 2007 - v3
Checksum:i8A8E76B75ABADE6D
GO
Isoform 2 (identifier: Q969S2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     79-94: Missing.

Note: No experimental confirmation available.
Show »
Length:316
Mass (Da):35,247
Checksum:i3183DDC0C41936DC
GO
Isoform 3 (identifier: Q969S2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.

Note: No experimental confirmation available.
Show »
Length:271
Mass (Da):29,930
Checksum:iA23E2B89F5256AE6
GO
Isoform 4 (identifier: Q969S2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     48-163: Missing.

Note: No experimental confirmation available.
Show »
Length:216
Mass (Da):24,136
Checksum:i250E84C5B5DAF3CB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02058570T → S.1 PublicationCorresponds to variant rs8191611dbSNPEnsembl.1
Natural variantiVAR_020586103R → Q.2 PublicationsCorresponds to variant rs8191613dbSNPEnsembl.1
Natural variantiVAR_020587103R → W.1 PublicationCorresponds to variant rs8191612dbSNPEnsembl.1
Natural variantiVAR_020588257R → L.1 PublicationCorresponds to variant rs8191664dbSNPEnsembl.1
Natural variantiVAR_020589304P → T.1 PublicationCorresponds to variant rs8191666dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0122081 – 61Missing in isoform 3. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_04334348 – 163Missing in isoform 4. 1 PublicationAdd BLAST116
Alternative sequenceiVSP_01220979 – 94Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079070 mRNA. Translation: BAC06478.1.
AK056206 mRNA. Translation: BAB71120.1.
AK097389 mRNA. Translation: BAC05030.1.
AK294224 mRNA. Translation: BAG57528.1.
BX537529 mRNA. Translation: CAD97774.1.
AY306127 Genomic DNA. Translation: AAP45052.1.
AC069185 Genomic DNA. No translation available.
BC013952 mRNA. Translation: AAH13952.1.
BC013964 mRNA. Translation: AAH13964.1.
CCDSiCCDS47802.1. [Q969S2-4]
CCDS47803.1. [Q969S2-3]
CCDS5984.1. [Q969S2-1]
RefSeqiNP_001129218.1. NM_001135746.1. [Q969S2-1]
NP_001129219.1. NM_001135747.1. [Q969S2-3]
NP_001129220.1. NM_001135748.1. [Q969S2-4]
NP_659480.1. NM_145043.2. [Q969S2-1]
XP_005272439.1. XM_005272382.2. [Q969S2-3]
XP_005272440.1. XM_005272383.2. [Q969S2-3]
XP_016868790.1. XM_017013301.1. [Q969S2-3]
UniGeneiHs.293818.

Genome annotation databases

EnsembliENST00000284503; ENSP00000284503; ENSG00000154328. [Q969S2-1]
ENST00000403422; ENSP00000384070; ENSG00000154328. [Q969S2-3]
ENST00000436750; ENSP00000394023; ENSG00000154328. [Q969S2-1]
ENST00000455213; ENSP00000397538; ENSG00000154328. [Q969S2-1]
ENST00000528323; ENSP00000435657; ENSG00000154328. [Q969S2-4]
GeneIDi252969.
KEGGihsa:252969.
UCSCiuc003wue.3. human. [Q969S2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079070 mRNA. Translation: BAC06478.1.
AK056206 mRNA. Translation: BAB71120.1.
AK097389 mRNA. Translation: BAC05030.1.
AK294224 mRNA. Translation: BAG57528.1.
BX537529 mRNA. Translation: CAD97774.1.
AY306127 Genomic DNA. Translation: AAP45052.1.
AC069185 Genomic DNA. No translation available.
BC013952 mRNA. Translation: AAH13952.1.
BC013964 mRNA. Translation: AAH13964.1.
CCDSiCCDS47802.1. [Q969S2-4]
CCDS47803.1. [Q969S2-3]
CCDS5984.1. [Q969S2-1]
RefSeqiNP_001129218.1. NM_001135746.1. [Q969S2-1]
NP_001129219.1. NM_001135747.1. [Q969S2-3]
NP_001129220.1. NM_001135748.1. [Q969S2-4]
NP_659480.1. NM_145043.2. [Q969S2-1]
XP_005272439.1. XM_005272382.2. [Q969S2-3]
XP_005272440.1. XM_005272383.2. [Q969S2-3]
XP_016868790.1. XM_017013301.1. [Q969S2-3]
UniGeneiHs.293818.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VZPmodel-A192-319[»]
ProteinModelPortaliQ969S2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128946. 6 interactors.
IntActiQ969S2. 7 interactors.
MINTiMINT-4720021.
STRINGi9606.ENSP00000284503.

PTM databases

iPTMnetiQ969S2.
PhosphoSitePlusiQ969S2.

Polymorphism and mutation databases

BioMutaiNEIL2.
DMDMi56404653.

Proteomic databases

MaxQBiQ969S2.
PaxDbiQ969S2.
PeptideAtlasiQ969S2.
PRIDEiQ969S2.

Protocols and materials databases

DNASUi252969.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000284503; ENSP00000284503; ENSG00000154328. [Q969S2-1]
ENST00000403422; ENSP00000384070; ENSG00000154328. [Q969S2-3]
ENST00000436750; ENSP00000394023; ENSG00000154328. [Q969S2-1]
ENST00000455213; ENSP00000397538; ENSG00000154328. [Q969S2-1]
ENST00000528323; ENSP00000435657; ENSG00000154328. [Q969S2-4]
GeneIDi252969.
KEGGihsa:252969.
UCSCiuc003wue.3. human. [Q969S2-1]

Organism-specific databases

CTDi252969.
DisGeNETi252969.
GeneCardsiNEIL2.
HGNCiHGNC:18956. NEIL2.
HPAiCAB017713.
MIMi608933. gene.
neXtProtiNX_Q969S2.
OpenTargetsiENSG00000154328.
PharmGKBiPA38769.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJ89. Eukaryota.
ENOG4112BNS. LUCA.
GeneTreeiENSGT00730000110955.
HOGENOMiHOG000069913.
HOVERGENiHBG082014.
InParanoidiQ969S2.
KOiK10568.
OMAiFLVFYNC.
OrthoDBiEOG091G0G2K.
PhylomeDBiQ969S2.
TreeFamiTF331502.

Enzyme and pathway databases

BioCyciZFISH:HS07973-MONOMER.
BRENDAi3.2.2.23. 2681.
ReactomeiR-HSA-110328. Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
R-HSA-110329. Cleavage of the damaged pyrimidine.
R-HSA-5649702. APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.

Miscellaneous databases

ChiTaRSiNEIL2. human.
GeneWikiiNEIL2.
GenomeRNAii252969.
PROiQ969S2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154328.
CleanExiHS_NEIL2.
ExpressionAtlasiQ969S2. baseline and differential.
GenevisibleiQ969S2. HS.

Family and domain databases

InterProiIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. FPG_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
[Graphical view]
PfamiPF06831. H2TH. 1 hit.
[Graphical view]
SMARTiSM01232. H2TH. 1 hit.
[Graphical view]
SUPFAMiSSF46946. SSF46946. 1 hit.
PROSITEiPS51068. FPG_CAT. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEIL2_HUMAN
AccessioniPrimary (citable) accession number: Q969S2
Secondary accession number(s): B4DFR7
, Q7Z3Q7, Q8N842, Q8NG52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 133 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.