Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q969S2 (NEIL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NEIL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length332 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.10

Catalytic activity

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.

Enzyme regulation

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

Subunit structure

Binds EP300.

Subcellular location

Nucleus Ref.7.

Tissue specificity

Detected in testis, skeletal muscle, heart, brain, placenta, lung, pancreas, kidney and liver. Ref.7

Domain

The zinc-finger domain is important for DNA binding.

Sequence similarities

Belongs to the FPG family.

Contains 1 FPG-type zinc finger.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q969S2-1)

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.
Isoform 2 (identifier: Q969S2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     79-94: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q969S2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q969S2-4)

The sequence of this isoform differs from the canonical sequence as follows:
     48-163: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 332331Endonuclease 8-like 2
PRO_0000170908

Regions

Zinc finger284 – 32037FPG-type

Sites

Active site21Schiff-base intermediate with DNA Probable
Active site31Proton donor Probable
Active site501Proton donor; for beta-elimination activity Probable
Active site3101Proton donor; for delta-elimination activity Probable
Binding site2311DNA By similarity

Amino acid modifications

Modified residue501N6-acetyllysine Ref.9
Modified residue1541N6-acetyllysine Ref.9

Natural variations

Alternative sequence1 – 6161Missing in isoform 3.
VSP_012208
Alternative sequence48 – 163116Missing in isoform 4.
VSP_043343
Alternative sequence79 – 9416Missing in isoform 2.
VSP_012209
Natural variant701T → S. Ref.4
Corresponds to variant rs8191611 [ dbSNP | Ensembl ].
VAR_020585
Natural variant1031R → Q. Ref.1 Ref.4
Corresponds to variant rs8191613 [ dbSNP | Ensembl ].
VAR_020586
Natural variant1031R → W. Ref.4
Corresponds to variant rs8191612 [ dbSNP | Ensembl ].
VAR_020587
Natural variant2571R → L. Ref.4
Corresponds to variant rs8191664 [ dbSNP | Ensembl ].
VAR_020588
Natural variant3041P → T. Ref.4
Corresponds to variant rs8191666 [ dbSNP | Ensembl ].
VAR_020589

Experimental info

Mutagenesis501K → R: Loss of glycosylase and AP lyase activity. Ref.8 Ref.9
Mutagenesis1541K → R: No effect on glycosylase and AP lyase activity. Ref.9
Mutagenesis2911C → S: Loss of glycosylase and AP lyase activity. Ref.10
Mutagenesis2951H → A: Loss of glycosylase and AP lyase activity. Ref.10
Mutagenesis3101R → Q: Strongly reduces strand AP lyase activity. Ref.10
Mutagenesis3151C → S: Loss of glycosylase and AP lyase activity. Ref.10
Mutagenesis3181C → S: Loss of glycosylase and AP lyase activity. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 8A8E76B75ABADE6D

FASTA33236,826
        10         20         30         40         50         60 
MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVHGK KLFLRFDLDE 

        70         80         90        100        110        120 
EMGPPGSSPT PEPPQKEVQK EGAADPKQVG EPSGQKTLDG SSRSAELVPQ GEDDSEYLER 

       130        140        150        160        170        180 
DAPAGDAGRW LRVSFGLFGS VWVNDFSRAK KANKRGDWRD PSPRLVLHFG GGGFLAFYNC 

       190        200        210        220        230        240 
QLSWSSSPVV TPTCDILSEK FHRGQALEAL GQAQPVCYTL LDQRYFSGLG NIIKNEALYR 

       250        260        270        280        290        300 
AGIHPLSLGS VLSASRREVL VDHVVEFSTA WLQGKFQGRP QHTQVYQKEQ CPAGHQVMKE 

       310        320        330 
AFGPEDGLQR LTWWCPQCQP QLSEEPEQCQ FS 

« Hide

Isoform 2 [UniParc].

Checksum: 3183DDC0C41936DC
Show »

FASTA31635,247
Isoform 3 [UniParc].

Checksum: A23E2B89F5256AE6
Show »

FASTA27129,930
Isoform 4 [UniParc].

Checksum: 250E84C5B5DAF3CB
Show »

FASTA21624,136

References

« Hide 'large scale' references
[1]"A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue."
Takao M., Kanno S., Kobayashi K., Zhang Q.-M., Yonei S., van der Horst G.T.J., Yasui A.
J. Biol. Chem. 277:42205-42213(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-103.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Tissue: Amygdala and Testis.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Fetal kidney.
[4]NIEHS SNPs program
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-70; GLN-103; TRP-103; LEU-257 AND THR-304.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[7]"Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions."
Hazra T.K., Kow Y.W., Hatahet Z., Imhoff B., Boldogh I., Mokkapati S.K., Mitra S., Izumi T.
J. Biol. Chem. 277:30417-30420(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-10, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2."
Dou H., Mitra S., Hazra T.K.
J. Biol. Chem. 278:49679-49684(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-50.
[9]"Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity."
Bhakat K.K., Hazra T.K., Mitra S.
Nucleic Acids Res. 32:3033-3039(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 40-57 AND 142-161, FUNCTION, MUTAGENESIS OF LYS-50 AND LYS-154, INTERACTION WITH EP300, ACETYLATION AT LYS-50 AND LYS-154.
[10]"Identification of a zinc finger domain in the human NEIL2 (Nei-like-2) protein."
Das A., Rajagopalan L., Mathura V.S., Rigby S.J., Mitra S., Hazra T.K.
J. Biol. Chem. 279:47132-47138(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-291; HIS-295; ARG-310; CYS-315 AND CYS-318, FUNCTION, IDENTIFICATION OF ZINC-FINGER, ZINC-BINDING, 3D-STRUCTURE MODELING OF 192-319, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001129218.1. NM_001135746.1.
NP_001129219.1. NM_001135747.1.
NP_001129220.1. NM_001135748.1.
NP_659480.1. NM_145043.2.
XP_005272438.1. XM_005272381.1.
XP_005272439.1. XM_005272382.1.
XP_005272440.1. XM_005272383.1.
UniGeneHs.293818.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VZPmodel-A192-319[»]
ProteinModelPortalQ969S2.
SMRQ969S2. Positions 3-320.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128946. 4 interactions.
MINTMINT-4720021.
STRING9606.ENSP00000284503.

PTM databases

PhosphoSiteQ969S2.

Polymorphism databases

DMDM56404653.

Proteomic databases

PaxDbQ969S2.
PRIDEQ969S2.

Protocols and materials databases

DNASU252969.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284503; ENSP00000284503; ENSG00000154328. [Q969S2-1]
ENST00000403422; ENSP00000384070; ENSG00000154328. [Q969S2-3]
ENST00000436750; ENSP00000394023; ENSG00000154328. [Q969S2-1]
ENST00000455213; ENSP00000397538; ENSG00000154328. [Q969S2-1]
ENST00000528323; ENSP00000435657; ENSG00000154328. [Q969S2-4]
GeneID252969.
KEGGhsa:252969.
UCSCuc003wue.2. human. [Q969S2-1]
uc011kxd.1. human. [Q969S2-4]

Organism-specific databases

CTD252969.
GeneCardsGC08P011627.
HGNCHGNC:18956. NEIL2.
MIM608933. gene.
neXtProtNX_Q969S2.
PharmGKBPA38769.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG73546.
HOGENOMHOG000069913.
HOVERGENHBG082014.
InParanoidQ969S2.
KOK10568.
OMAGHQVMKE.
OrthoDBEOG7Z69CR.
PhylomeDBQ969S2.
TreeFamTF331502.

Gene expression databases

ArrayExpressQ969S2.
BgeeQ969S2.
CleanExHS_NEIL2.
GenevestigatorQ969S2.

Family and domain databases

InterProIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
[Graphical view]
PfamPF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
[Graphical view]
SUPFAMSSF46946. SSF46946. 1 hit.
PROSITEPS51068. FPG_CAT. 1 hit.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNEIL2. human.
GeneWikiNEIL2.
GenomeRNAi252969.
NextBio92030.
PROQ969S2.
SOURCESearch...

Entry information

Entry nameNEIL2_HUMAN
AccessionPrimary (citable) accession number: Q969S2
Secondary accession number(s): B4DFR7 expand/collapse secondary AC list , Q7Z3Q7, Q8N842, Q8NG52
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 108 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM