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Protein

Endonuclease 8-like 2

Gene

NEIL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

Activity 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

Keywordsi

Molecular functionDNA-binding, Glycosidase, Hydrolase, Lyase, Multifunctional enzyme
Biological processDNA damage, DNA repair
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000154328.15
HGNCiHGNC:18956 NEIL2
MIMi608933 gene
neXtProtiNX_Q969S2

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
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

EPDiQ969S2
MaxQBiQ969S2
PaxDbiQ969S2
PeptideAtlasiQ969S2
PRIDEiQ969S2
ProteomicsDBi75827
75828 [Q969S2-2]
75829 [Q969S2-3]
75830 [Q969S2-4]

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 Expressed in 183 organ(s), highest expression level in female gonad
CleanExiHS_NEIL2
ExpressionAtlasiQ969S2 baseline and differential
GenevisibleiQ969S2 HS

Organism-specific databases

HPAiHPA073029
HPA073916

Interactioni

Subunit structurei

Binds EP300.

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128946, 6 interactors
CORUMiQ969S2
IntActiQ969S2, 8 interactors
STRINGi9606.ENSP00000284503

Structurei

3D structure databases

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

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
OMAiSPFVGQQ
OrthoDBiEOG091G0G2K
PhylomeDBiQ969S2
TreeFamiTF331502

Family and domain databases

InterProiView protein in InterPro
IPR015886 DNA_glyclase/AP_lyase_DNA-bd
IPR012319 FPG_cat
IPR010979 Ribosomal_S13-like_H2TH
IPR000214 Znf_DNA_glyclase/AP_lyase
PfamiView protein in Pfam
PF06831 H2TH, 1 hit
SMARTiView protein in SMART
SM01232 H2TH, 1 hit
SUPFAMiSSF46946 SSF46946, 1 hit
PROSITEiView protein in PROSITE
PS51068 FPG_CAT, 1 hit
PS51066 ZF_FPG_2, 1 hit

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

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PPL4E9PPL4_HUMAN
Endonuclease 8-like 2
NEIL2
60Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02058570T → S1 PublicationCorresponds to variant dbSNP:rs8191611Ensembl.1
Natural variantiVAR_020586103R → Q2 PublicationsCorresponds to variant dbSNP:rs8191613Ensembl.1
Natural variantiVAR_020587103R → W1 PublicationCorresponds to variant dbSNP:rs8191612Ensembl.1
Natural variantiVAR_020588257R → L1 PublicationCorresponds to variant dbSNP:rs8191664Ensembl.1
Natural variantiVAR_020589304P → T1 PublicationCorresponds to variant dbSNP:rs8191666Ensembl.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

Similar proteinsi

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
CORUMiQ969S2
IntActiQ969S2, 8 interactors
STRINGi9606.ENSP00000284503

PTM databases

iPTMnetiQ969S2
PhosphoSitePlusiQ969S2

Polymorphism and mutation databases

BioMutaiNEIL2
DMDMi56404653

Proteomic databases

EPDiQ969S2
MaxQBiQ969S2
PaxDbiQ969S2
PeptideAtlasiQ969S2
PRIDEiQ969S2
ProteomicsDBi75827
75828 [Q969S2-2]
75829 [Q969S2-3]
75830 [Q969S2-4]

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
EuPathDBiHostDB:ENSG00000154328.15
GeneCardsiNEIL2
HGNCiHGNC:18956 NEIL2
HPAiHPA073029
HPA073916
MIMi608933 gene
neXtProtiNX_Q969S2
OpenTargetsiENSG00000154328
PharmGKBiPA38769
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
PROiPR:Q969S2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154328 Expressed in 183 organ(s), highest expression level in female gonad
CleanExiHS_NEIL2
ExpressionAtlasiQ969S2 baseline and differential
GenevisibleiQ969S2 HS

Family and domain databases

InterProiView protein in InterPro
IPR015886 DNA_glyclase/AP_lyase_DNA-bd
IPR012319 FPG_cat
IPR010979 Ribosomal_S13-like_H2TH
IPR000214 Znf_DNA_glyclase/AP_lyase
PfamiView protein in Pfam
PF06831 H2TH, 1 hit
SMARTiView protein in SMART
SM01232 H2TH, 1 hit
SUPFAMiSSF46946 SSF46946, 1 hit
PROSITEiView protein in PROSITE
PS51068 FPG_CAT, 1 hit
PS51066 ZF_FPG_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNEIL2_HUMAN
AccessioniPrimary (citable) accession number: Q969S2
Secondary accession number(s): B4DFR7
, Q7Z3Q7, Q8N842, Q8NG52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 148 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health

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