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Q8TAT5 (NEIL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:NEIL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length605 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.9 Ref.12 Ref.13

Catalytic activity

Removes damaged bases from DNA, leaving an abasic site. Ref.11 Ref.13

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. Ref.11 Ref.13

Subcellular location

Nucleus Ref.6.

Tissue specificity

Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts. Ref.6 Ref.7 Ref.8 Ref.11

Developmental stage

Up-regulated during early S phase of the cell cycle, and sustained through G/M phase. Low expression levels in quiescent cells. Ref.11

Domain

The N-terminal region (2-281) contains the glycosylase and lyase activities By similarity.

Sequence similarities

Belongs to the FPG family.

Contains 1 FPG-type zinc finger.

Contains 1 RanBP2-type zinc finger.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Probable
Chain2 – 605604Endonuclease 8-like 3
PRO_0000170910

Regions

Zinc finger247 – 28135FPG-type
Zinc finger317 – 34630RanBP2-type

Sites

Active site21Schiff-base intermediate with DNA; via amino nitrogen By similarity
Binding site1921DNA By similarity
Binding site2711DNA By similarity
Site21Important for monofunctional glycosylase activity
Site811Required for glycosylase and lyase activities

Natural variations

Natural variant381R → C. Ref.3
Corresponds to variant rs34007209 [ dbSNP | Ensembl ].
VAR_025806
Natural variant581N → NN. Ref.3
VAR_025807
Natural variant761V → M. Ref.3
Corresponds to variant rs34112288 [ dbSNP | Ensembl ].
VAR_025808
Natural variant1171P → R. Ref.3 Ref.5
Corresponds to variant rs7689099 [ dbSNP | Ensembl ].
VAR_020590
Natural variant1721Q → H. Ref.3
Corresponds to variant rs17064658 [ dbSNP | Ensembl ].
VAR_025809
Natural variant2861H → R. Ref.3
Corresponds to variant rs34193982 [ dbSNP | Ensembl ].
VAR_025810
Natural variant3461I → V. Ref.3
Corresponds to variant rs17064676 [ dbSNP | Ensembl ].
VAR_025811
Natural variant4431P → L. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs13112358 [ dbSNP | Ensembl ].
VAR_020591
Natural variant4711Q → H. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs13112390 [ dbSNP | Ensembl ].
VAR_025812
Natural variant5201G → R. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs1876268 [ dbSNP | Ensembl ].
VAR_020592
Natural variant5471A → S. Ref.3
Corresponds to variant rs36005630 [ dbSNP | Ensembl ].
VAR_025813
Natural variant5561H → R. Ref.3
Corresponds to variant rs35418725 [ dbSNP | Ensembl ].
VAR_025814

Experimental info

Mutagenesis21V → P: No effect on AP lyase activity. Impairs monofunctional glycosylase activity. Ref.9 Ref.13
Mutagenesis31E → A: No effect on AP lyase activity. Ref.9
Mutagenesis811K → A: Loss of glycosylase and lyase activities. Ref.13
Mutagenesis2761C → S: Abolishes AP lyase activity. Ref.9
Mutagenesis2791C → S: Abolishes AP lyase activity. Ref.9
Sequence conflict351L → P in BAA91860. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q8TAT5 [UniParc].

Last modified August 10, 2010. Version 3.
Checksum: 528B17873ABC9D89

FASTA60567,769
        10         20         30         40         50         60 
MVEGPGCTLN GEKIRARVLP GQAVTGVRGS ALRSLQGRAL RLAASTVVVS PQAAALNNDS 

        70         80         90        100        110        120 
SQNVLSLFNG YVYSGVETLG KELFMYFGPK ALRIHFGMKG FIMINPLEYK YKNGASPVLE 

       130        140        150        160        170        180 
VQLTKDLICF FDSSVELRNS MESQQRIRMM KELDVCSPEF SFLRAESEVK KQKGRMLGDV 

       190        200        210        220        230        240 
LMDQNVLPGV GNIIKNEALF DSGLHPAVKV CQLTDEQIHH LMKMIRDFSI LFYRCRKAGL 

       250        260        270        280        290        300 
ALSKHYKVYK RPNCGQCHCR ITVCRFGDNN RMTYFCPHCQ KENPQHVDIC KLPTRNTIIS 

       310        320        330        340        350        360 
WTSSRVDHVM DSVARKSEEH WTCVVCTLIN KPSSKACDAC LTSRPIDSVL KSEENSTVFS 

       370        380        390        400        410        420 
HLMKYPCNTF GKPHTEVKIN RKTAFGTTTL VLTDFSNKSS TLERKTKQNQ ILDEEFQNSP 

       430        440        450        460        470        480 
PASVCLNDIQ HPSKKTTNDI TQPSSKVNIS PTISSESKLF SPAHKKPKTA QYSSPELKSC 

       490        500        510        520        530        540 
NPGYSNSELQ INMTDGPRTL NPDSPRCSKH NRLCILRVVG KDGENKGRQF YACPLPREAQ 

       550        560        570        580        590        600 
CGFFEWADLS FPFCNHGKRS TMKTVLKIGP NNGKNFFVCP LGKEKQCNFF QWAENGPGIK 


IIPGC 

« Hide

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], VARIANTS LEU-443; HIS-471 AND ARG-520.
Tissue: Skin.
[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], VARIANTS LEU-443; HIS-471 AND ARG-520.
[3]NIEHS SNPs program
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-38; ASN-58 INS; MET-76; ARG-117; HIS-172; ARG-286; VAL-346; LEU-443; HIS-471; ARG-520; SER-547 AND ARG-556.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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], VARIANTS ARG-117; LEU-443; HIS-471 AND ARG-520.
Tissue: B-cell.
[6]"Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA."
Morland I., Rolseth V., Luna L., Rognes T., Bjoeraas M., Seeberg E.
Nucleic Acids Res. 30:4926-4936(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein."
Torisu K., Tsuchimoto D., Ohnishi Y., Nakabeppu Y.
J. Biochem. 138:763-772(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Expression patterns of Neil3 during embryonic brain development and neoplasia."
Hildrestrand G.A., Neurauter C.G., Diep D.B., Castellanos C.G., Krauss S., Bjoras M., Luna L.
BMC Neurosci. 10:45-45(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Human Nei-like protein NEIL3 has AP lyase activity specific for single-stranded DNA and confers oxidative stress resistance in Escherichia coli mutant."
Takao M., Oohata Y., Kitadokoro K., Kobayashi K., Iwai S., Yasui A., Yonei S., Zhang Q.M.
Genes Cells 14:261-270(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF VAL-2; GLU-3; CYS-276 AND CYS-279.
[10]"Expression and purification of NEIL3, a human DNA glycosylase homolog."
Krokeide S.Z., Bolstad N., Laerdahl J.K., Bjoras M., Luna L.
Protein Expr. Purif. 65:160-164(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
[11]"Release from quiescence stimulates the expression of human NEIL3 under the control of the Ras dependent ERK-MAP kinase pathway."
Neurauter C.G., Luna L., Bjoras M.
DNA Repair 11:401-409(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[12]"Expression and purification of active mouse and human NEIL3 proteins."
Liu M., Bandaru V., Holmes A., Averill A.M., Cannan W., Wallace S.S.
Protein Expr. Purif. 84:130-139(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A GLYCOSYLASE, PROBABLE CLEAVAGE OF INITIATOR METHIONINE.
[13]"Human NEIL3 is mainly a monofunctional DNA glycosylase removing spiroimindiohydantoin and guanidinohydantoin."
Krokeide S.Z., Laerdahl J.K., Salah M., Luna L., Cederkvist F.H., Fleming A.M., Burrows C.J., Dalhus B., Bjoras M.
DNA Repair 12:1159-1164(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, PROBABLE CLEAVAGE OF INITIATOR METHIONINE, MUTAGENESIS OF VAL-2 AND LYS-81.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3828.1.
RefSeqNP_060718.2. NM_018248.2.
UniGeneHs.405467.

3D structure databases

ProteinModelPortalQ8TAT5.
SMRQ8TAT5. Positions 2-281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120538. 2 interactions.
STRING9606.ENSP00000264596.

PTM databases

PhosphoSiteQ8TAT5.

Polymorphism databases

DMDM302393810.

Proteomic databases

MaxQBQ8TAT5.
PaxDbQ8TAT5.
PRIDEQ8TAT5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264596; ENSP00000264596; ENSG00000109674.
GeneID55247.
KEGGhsa:55247.
UCSCuc003iut.2. human.

Organism-specific databases

CTD55247.
GeneCardsGC04P178230.
HGNCHGNC:24573. NEIL3.
MIM608934. gene.
neXtProtNX_Q8TAT5.
PharmGKBPA134889634.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0266.
HOGENOMHOG000113754.
HOVERGENHBG052594.
InParanoidQ8TAT5.
KOK10569.
OMAICFFDSS.
OrthoDBEOG7W153D.
PhylomeDBQ8TAT5.
TreeFamTF331502.

Gene expression databases

ArrayExpressQ8TAT5.
BgeeQ8TAT5.
CleanExHS_NEIL3.
GenevestigatorQ8TAT5.

Family and domain databases

InterProIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR015887. DNA_glyclase_Znf_dom_DNA_BS.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR010979. Ribosomal_S13-like_H2TH.
IPR000214. Znf_DNA_glyclase/AP_lyase.
IPR010666. Znf_GRF.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamPF06831. H2TH. 1 hit.
PF06839. zf-GRF. 2 hits.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
SMARTSM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMSSF46946. SSF46946. 1 hit.
SSF81624. SSF81624. 1 hit.
PROSITEPS51068. 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.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNEIL3_(gene).
GenomeRNAi55247.
NextBio59296.
PROQ8TAT5.
SOURCESearch...

Entry information

Entry nameNEIL3_HUMAN
AccessionPrimary (citable) accession number: Q8TAT5
Secondary accession number(s): Q2PPJ3, Q8NG51, Q9NV95
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: August 10, 2010
Last modified: July 9, 2014
This is version 104 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

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 4

Human chromosome 4: entries, gene names and cross-references to MIM