UniProt Accession

 NEIL3_HUMAN; Q8TAT5; Q2PPJ3; Q8NG51; Q9NV95 

Genbank Protein ID

 AB079071; AK001720; DQ310721; AC027627; BC025954 

Genbank Nucleotide ID

 BAC06479.1; BAA91860.1; ABC40719.1; AAH25954.1 

Protein Name

 Endonuclease 8-like 3 

Protein Synonyms/Alias

 DNA glycosylase FPG2; DNA glycosylase/AP lyase Neil3; Endonuclease VIII-like 3; Nei-like protein 3 

Gene Name

 NEIL3 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
13	GCTLNGEKIRARVLP	ubiquitination	[1]
90	LFMYFGPKALRIHFG	ubiquitination	[1]
110	MINPLEYKYKNGASP	ubiquitination	[1, 2, 3, 4]
112	NPLEYKYKNGASPVL	ubiquitination	[1, 5]
151	QQRIRMMKELDVCSP	ubiquitination	[1, 4, 5]
195	PGVGNIIKNEALFDS	ubiquitination	[1]
209	SGLHPAVKVCQLTDE	ubiquitination	[1]
223	EQIHHLMKMIRDFSI	ubiquitination	[1]
237	ILFYRCRKAGLALSK	ubiquitination	[1]
244	KAGLALSKHYKVYKR	ubiquitination	[1, 5]
247	LALSKHYKVYKRPNC	ubiquitination	[1]
281	YFCPHCQKENPQHVD	ubiquitination	[1]
291	PQHVDICKLPTRNTI	ubiquitination	[1, 5]
316	VMDSVARKSEEHWTC	ubiquitination	[1]
331	VVCTLINKPSSKACD	ubiquitination	[1]
351	RPIDSVLKSEENSTV	ubiquitination	[1, 4, 5]
364	TVFSHLMKYPCNTFG	ubiquitination	[1]
372	YPCNTFGKPHTEVKI	ubiquitination	[1, 5]
378	GKPHTEVKINRKTAF	ubiquitination	[1]
382	TEVKINRKTAFGTTT	ubiquitination	[1]
398	VLTDFSNKSSTLERK	ubiquitination	[1, 3, 4, 5]
407	STLERKTKQNQILDE	ubiquitination	[1]
434	NDIQHPSKKTTNDIT	ubiquitination	[1]
435	DIQHPSKKTTNDITQ	ubiquitination	[1, 6]
446	DITQPSSKVNISPTI	ubiquitination	[3]
465	KLFSPAHKKPKTAQY	ubiquitination	[1]
466	LFSPAHKKPKTAQYS	ubiquitination	[1]
468	SPAHKKPKTAQYSSP	ubiquitination	[1]
558	FPFCNHGKRSTMKTV	ubiquitination	[1]
563	HGKRSTMKTVLKIGP	ubiquitination	[1]
567	STMKTVLKIGPNNGK	ubiquitination	[1, 3, 5]
574	KIGPNNGKNFFVCPL	ubiquitination	[1, 5, 6]
583	FFVCPLGKEKQCNFF	ubiquitination	[1]
585	VCPLGKEKQCNFFQW	ubiquitination	[1, 5, 6]
600	AENGPGIKIIPGC**	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 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 PubMed:19170771 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. 

Sequence Annotation

 ZN_FING 247 281 FPG-type.
 ZN_FING 317 346 RanBP2-type.
 ACT_SITE 2 2 Schiff-base intermediate with DNA; via
 BINDING 192 192 DNA (By similarity).
 BINDING 271 271 DNA (By similarity).  

Keyword

 Complete proteome; DNA damage; DNA repair; DNA-binding; Glycosidase; Hydrolase; Lyase; Metal-binding; Multifunctional enzyme; Nucleus; Polymorphism; Reference proteome; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 605 AA 

Protein Sequence

Gene Ontology

 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0000405; F:bubble DNA binding; ISS:UniProtKB.
 GO:0003684; F:damaged DNA binding; IEA:InterPro.
 GO:0019104; F:DNA N-glycosylase activity; ISS:UniProtKB.
 GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase activity; IDA:UniProtKB.
 GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
 GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006284; P:base-excision repair; ISS:UniProtKB.
 GO:0006289; P:nucleotide-excision repair; IEA:InterPro. 

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. 

Pfam

 PF06831; H2TH
 PF06839; zf-GRF
 PF00641; zf-RanBP 

SMART

 SM00547; ZnF_RBZ 

PROSITE

 PS51068; FPG_CAT
 PS01242; ZF_FPG_1
 PS51066; ZF_FPG_2
 PS01358; ZF_RANBP2_1
 PS50199; ZF_RANBP2_2 

PRINTS