Q8TAT5 (NEIL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	605 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reports about DNA glycosylase activity are contradictory. A number of references report finding no DNA glycosylase activity and the protein lacks a proline residue at the N-terminus which functions as an active site residue in other members of the FPG family. However, the mouse ortholog has been shown to have both DNA glycosylase and AP lyase activities and Ref.9 demonstrates AP lyase activity. Prefers single-stranded DNA or partially single-stranded DNA structures such as bubble and fork structures to double-stranded DNA in vitro. Displays a broad recognition spectrum, preferring FapyA and FapyG followed by 5-OHU, 5-PHC and 5-OHMH and then Tg and 8-oxoA. No activity on 8-oxoG detected. Ref.1 Ref.6 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.
Subcellular location	Nucleus Ref.6.
Tissue specificity	Detected in thymus and testis. Expressed at higher levels in tumor tissue than in the corresponding normal tissues except for pancreas and testis where expression is higher in normal than tumor tissue. Ref.6 Ref.7 Ref.8
Sequence similarities	Belongs to the FPG family. Contains 1 FPG-type zinc finger. Contains 1 RanBP2-type zinc finger.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Glycosidase Hydrolase Lyase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	base-excision repair Inferred from sequence or structural similarity. Source: UniProtKB nucleotide-excision repair Inferred from electronic annotation. Source: InterPro
Cellular_component	nucleus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	DNA N-glycosylase activity Inferred from sequence or structural similarity. Source: UniProtKB DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay Ref.9. Source: UniProtKB bubble DNA binding Inferred from sequence or structural similarity. Source: UniProtKB damaged DNA binding Inferred from electronic annotation. Source: InterPro double-stranded DNA binding Inferred from sequence or structural similarity. Source: UniProtKB single-stranded DNA binding Inferred from direct assay Ref.9. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 605	604	Endonuclease 8-like 3		PRO_0000170910
Regions
	Zinc finger	247 – 281	35	FPG-type
	Zinc finger	317 – 346	30	RanBP2-type
Sites
	Active site	2	1	Schiff-base intermediate with DNA; via amino nitrogen By similarity
	Binding site	192	1	DNA By similarity
	Binding site	271	1	DNA By similarity
Natural variations
	Natural variant	38	1	R → C. Ref.3 Corresponds to variant rs34007209 [ dbSNP | Ensembl ].		VAR_025806
	Natural variant	58	1	N → NN. Ref.3		VAR_025807
	Natural variant	76	1	V → M. Ref.3 Corresponds to variant rs34112288 [ dbSNP | Ensembl ].		VAR_025808
	Natural variant	117	1	P → R. Ref.3 Ref.5 Corresponds to variant rs7689099 [ dbSNP | Ensembl ].		VAR_020590
	Natural variant	172	1	Q → H. Ref.3 Corresponds to variant rs17064658 [ dbSNP | Ensembl ].		VAR_025809
	Natural variant	286	1	H → R. Ref.3 Corresponds to variant rs34193982 [ dbSNP | Ensembl ].		VAR_025810
	Natural variant	346	1	I → V. Ref.3 Corresponds to variant rs17064676 [ dbSNP | Ensembl ].		VAR_025811
	Natural variant	443	1	P → L. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs13112358 [ dbSNP | Ensembl ].		VAR_020591
	Natural variant	471	1	Q → H. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs13112390 [ dbSNP | Ensembl ].		VAR_025812
	Natural variant	520	1	G → R. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs1876268 [ dbSNP | Ensembl ].		VAR_020592
	Natural variant	547	1	A → S. Ref.3 Corresponds to variant rs36005630 [ dbSNP | Ensembl ].		VAR_025813
	Natural variant	556	1	H → R. Ref.3 Corresponds to variant rs35418725 [ dbSNP | Ensembl ].		VAR_025814
Experimental info
	Mutagenesis	2	1	V → P: No effect on AP lyase activity. Ref.9
	Mutagenesis	3	1	E → A: No effect on AP lyase activity. Ref.9
	Mutagenesis	276	1	C → S: Abolishes AP lyase activity. Ref.9
	Mutagenesis	279	1	C → S: Abolishes AP lyase activity. Ref.9
	Sequence conflict	35	1	L → P in BAA91860. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8TAT5 [UniParc]. Last modified August 10, 2010. Version 3. Checksum: 528B17873ABC9D89	FASTA	605	67,769
	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

References

	« Hide 'large scale' referencesShow '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], LACK OF GLYCOSYLASE FUNCTION, 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. , 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. , 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: LACK OF GLYCOSYLASE FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

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.
IPI	IPI00303135.
RefSeq	NP_060718.2. NM_018248.2.
UniGene	Hs.405467.
3D structure databases
ProteinModelPortal	Q8TAT5.
SMR	Q8TAT5. Positions 70-284.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000264596.
PTM databases
PhosphoSite	Q8TAT5.
Polymorphism databases
DMDM	302393810.
Proteomic databases
PaxDb	Q8TAT5.
PRIDE	Q8TAT5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264596; ENSP00000264596; ENSG00000109674.
GeneID	55247.
KEGG	hsa:55247.
UCSC	uc003iut.2. human.
Organism-specific databases
CTD	55247.
GeneCards	GC04P178230.
HGNC	HGNC:24573. NEIL3.
MIM	608934. gene.
neXtProt	NX_Q8TAT5.
PharmGKB	PA134889634.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0266.
HOGENOM	HOG000113754.
HOVERGEN	HBG052594.
InParanoid	Q8TAT5.
KO	K10569.
OMA	TKDLICF.
OrthoDB	EOG48GW30.
PhylomeDB	Q8TAT5.
Gene expression databases
ArrayExpress	Q8TAT5.
Bgee	Q8TAT5.
CleanEx	HS_NEIL3.
Genevestigator	Q8TAT5.
GermOnline	ENSG00000109674. Homo sapiens.
Family and domain databases
InterPro	IPR015886. 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]
Pfam	PF06831. H2TH. 1 hit. PF06839. zf-GRF. 2 hits. PF00641. zf-RanBP. 1 hit. [Graphical view]
SMART	SM00547. ZnF_RBZ. 1 hit. [Graphical view]
SUPFAM	SSF81624. Form_DNAglyc_cat. 1 hit. SSF46946. Ribosomal_H2TH. 1 hit.
PROSITE	PS51068. 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]
ProtoNet	Search...
Other
GenomeRNAi	55247.
NextBio	59296.
SOURCE	Search...

Entry information

Entry name

NEIL3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.