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Protein

Endonuclease 8-like 1

Gene

NEIL1

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. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 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. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2Schiff-base intermediate with DNACurated1
Active sitei3Proton donorCurated1
Active sitei54Proton donor; for beta-elimination activityCurated1
Binding sitei176DNABy similarity1
Active sitei339Proton donor; for delta-elimination activityCurated1
Binding sitei339DNABy similarity1

GO - Molecular functioni

GO - Biological processi

  • base-excision repair Source: UniProtKB
  • depyrimidination Source: Reactome
  • negative regulation of nuclease activity Source: UniProtKB
  • nucleotide-excision repair Source: InterPro
  • response to oxidative stress Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

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
SIGNORiQ96FI4

Names & Taxonomyi

Protein namesi
Recommended name:
Endonuclease 8-like 1 (EC:3.2.2.-, EC:4.2.99.18)
Alternative name(s):
DNA glycosylase/AP lyase Neil1
DNA-(apurinic or apyrimidinic site) lyase Neil1
Endonuclease VIII-like 1
FPG1
Nei homolog 1
Short name:
NEH1
Nei-like protein 1
Gene namesi
Name:NEIL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000140398.13
HGNCiHGNC:18448 NEIL1
MIMi608844 gene
neXtProtiNX_Q96FI4

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

Chromosome, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2P → T: Loss of glycosylase and AP lyase activity. 2 Publications1
Mutagenesisi2Missing : Loss of glycosylase activity. 2 Publications1
Mutagenesisi3E → Q: Loss of glycosylase and AP lyase activity. 1 Publication1
Mutagenesisi54K → L: Loss of glycosylase activity. 1 Publication1
Mutagenesisi277R → A: Strongly reduced glycosylase activity. Has little effect on AP lyase activity. 1 Publication1

Organism-specific databases

DisGeNETi79661
OpenTargetsiENSG00000140398
PharmGKBiPA38334

Chemistry databases

DrugBankiDB03754 Tris

Polymorphism and mutation databases

BioMutaiNEIL1
DMDMi56404654

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00001709052 – 390Endonuclease 8-like 1Add BLAST389

Proteomic databases

EPDiQ96FI4
PaxDbiQ96FI4
PeptideAtlasiQ96FI4
PRIDEiQ96FI4
ProteomicsDBi76532

PTM databases

iPTMnetiQ96FI4
PhosphoSitePlusiQ96FI4

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Inductioni

Up-regulated during S-phase.1 Publication

Gene expression databases

BgeeiENSG00000140398
CleanExiHS_NEIL1
ExpressionAtlasiQ96FI4 baseline and differential
GenevisibleiQ96FI4 HS

Organism-specific databases

HPAiHPA054084

Interactioni

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122787, 6 interactors
CORUMiQ96FI4
STRINGi9606.ENSP00000347170

Structurei

Secondary structure

1390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 18Combined sources15
Beta strandi23 – 26Combined sources4
Beta strandi41 – 52Combined sources12
Beta strandi55 – 62Combined sources8
Beta strandi73 – 78Combined sources6
Turni80 – 82Combined sources3
Beta strandi83 – 89Combined sources7
Helixi90 – 92Combined sources3
Beta strandi97 – 103Combined sources7
Beta strandi105 – 107Combined sources3
Beta strandi110 – 116Combined sources7
Beta strandi122 – 127Combined sources6
Turni137 – 139Combined sources3
Helixi141 – 150Combined sources10
Turni151 – 153Combined sources3
Helixi155 – 158Combined sources4
Helixi161 – 164Combined sources4
Turni168 – 170Combined sources3
Helixi176 – 186Combined sources11
Helixi194 – 198Combined sources5
Helixi199 – 201Combined sources3
Helixi212 – 218Combined sources7
Turni219 – 221Combined sources3
Helixi225 – 240Combined sources16
Helixi243 – 245Combined sources3
Helixi249 – 259Combined sources11
Beta strandi269 – 272Combined sources4
Beta strandi278 – 283Combined sources6

3D structure databases

ProteinModelPortaliQ96FI4
SMRiQ96FI4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96FI4

Family & Domainsi

Sequence similaritiesi

Belongs to the FPG family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IEAW Eukaryota
ENOG410ZTEH LUCA
GeneTreeiENSGT00390000016671
HOGENOMiHOG000067872
HOVERGENiHBG052592
InParanoidiQ96FI4
KOiK10567
OMAiHLASHFV
OrthoDBiEOG091G07LM
PhylomeDBiQ96FI4
TreeFamiTF333272

Family and domain databases

Gene3Di3.20.190.10, 1 hit
InterProiView protein in InterPro
IPR015886 DNA_glyclase/AP_lyase_DNA-bd
IPR015371 Endonuclease-VIII_DNA-bd
IPR012319 FPG_cat
IPR035937 MutM-like_N-ter
IPR010979 Ribosomal_S13-like_H2TH
PfamiView protein in Pfam
PF01149 Fapy_DNA_glyco, 1 hit
PF06831 H2TH, 1 hit
PF09292 Neil1-DNA_bind, 1 hit
SMARTiView protein in SMART
SM00898 Fapy_DNA_glyco, 1 hit
SM01232 H2TH, 1 hit
SUPFAMiSSF46946 SSF46946, 1 hit
SSF81624 SSF81624, 1 hit
PROSITEiView protein in PROSITE
PS51068 FPG_CAT, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q96FI4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPEGPELHLA SQFVNEACRA LVFGGCVEKS SVSRNPEVPF ESSAYRISAS
60 70 80 90 100
ARGKELRLIL SPLPGAQPQQ EPLALVFRFG MSGSFQLVPR EELPRHAHLR
110 120 130 140 150
FYTAPPGPRL ALCFVDIRRF GRWDLGGKWQ PGRGPCVLQE YQQFRENVLR
160 170 180 190 200
NLADKAFDRP ICEALLDQRF FNGIGNYLRA EILYRLKIPP FEKARSVLEA
210 220 230 240 250
LQQHRPSPEL TLSQKIRTKL QNPDLLELCH SVPKEVVQLG GKGYGSESGE
260 270 280 290 300
EDFAAFRAWL RCYGMPGMSS LQDRHGRTIW FQGDPGPLAP KGRKSRKKKS
310 320 330 340 350
KATQLSPEDR VEDALPPSKA PSRTRRAKRD LPKRTATQRP EGTSLQQDPE
360 370 380 390
APTVPKKGRR KGRQAASGHC RPRKVKADIP SLEPEGTSAS
Length:390
Mass (Da):43,684
Last modified:January 23, 2007 - v3
Checksum:iB2B058486C4EF835
GO

Sequence cautioni

The sequence AK128372 differs from that shown. Erroneous CDS prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147N → S in BAB15337 (PubMed:14702039).Curated1

RNA editingi

Edited at position 242.1 Publication
The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. The recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02058082S → C1 PublicationCorresponds to variant dbSNP:rs5745905Ensembl.1
Natural variantiVAR_02058183G → D1 PublicationCorresponds to variant dbSNP:rs5745906Ensembl.1
Natural variantiVAR_020582136C → R1 PublicationCorresponds to variant dbSNP:rs5745907Ensembl.1
Natural variantiVAR_065963159R → Q1 PublicationCorresponds to variant dbSNP:rs769880000Ensembl.1
Natural variantiVAR_065964181E → K Found in a patient with nephrotic syndrome also carrying mutation P-159 in MYO1E. 1 PublicationCorresponds to variant dbSNP:rs749636951Ensembl.1
Natural variantiVAR_020583182I → M. Corresponds to variant dbSNP:rs7183491Ensembl.1
Natural variantiVAR_065018242K → R in RNA edited version. 1
Natural variantiVAR_020584252D → N1 PublicationCorresponds to variant dbSNP:rs5745926Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079068 mRNA Translation: BAC06476.1
AK026055 mRNA Translation: BAB15337.1
AK128372 mRNA No translation available.
AY257544 Genomic DNA Translation: AAO74826.1
AC068338 Genomic DNA No translation available.
CH471136 Genomic DNA Translation: EAW99255.1
CH471136 Genomic DNA Translation: EAW99260.1
BC010876 mRNA Translation: AAH10876.1
CCDSiCCDS10278.1
RefSeqiNP_001243481.1, NM_001256552.1
NP_078884.2, NM_024608.3
XP_005254716.1, XM_005254659.4
XP_006720743.1, XM_006720680.1
XP_006720744.1, XM_006720681.1
XP_011520304.1, XM_011522002.1
XP_011520305.1, XM_011522003.2
XP_011520306.1, XM_011522004.2
UniGeneiHs.512732

Genome annotation databases

EnsembliENST00000355059; ENSP00000347170; ENSG00000140398
ENST00000564784; ENSP00000457352; ENSG00000140398
ENST00000569035; ENSP00000455730; ENSG00000140398
GeneIDi79661
KEGGihsa:79661
UCSCiuc002bad.5 human

Keywords - Coding sequence diversityi

Polymorphism, RNA editing

Similar proteinsi

Entry informationi

Entry nameiNEIL1_HUMAN
AccessioniPrimary (citable) accession number: Q96FI4
Secondary accession number(s): D3DW75
, Q6ZRA7, Q86XW7, Q9H6C3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 155 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, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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

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