Q969S2 (NEIL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	332 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	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.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Glycosidase Hydrolase Lyase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	base-excision repair Inferred from electronic annotation. Source: InterPro nucleotide-excision repair Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle microtubule Inferred from electronic annotation. Source: Compara
Molecular_function	DNA-(apurinic or apyrimidinic site) lyase activity Inferred from electronic annotation. Source: EC damaged DNA binding Inferred from electronic annotation. Source: InterPro hydrolase activity, hydrolyzing N-glycosyl compounds Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 332	331	Endonuclease 8-like 2		PRO_0000170908
Regions
	Zinc finger	284 – 320	37	FPG-type
Sites
	Active site	2	1	Schiff-base intermediate with DNA Probable
	Active site	3	1	Proton donor Probable
	Active site	50	1	Proton donor; for beta-elimination activity Probable
	Active site	310	1	Proton donor; for delta-elimination activity Probable
	Binding site	231	1	DNA By similarity
Amino acid modifications
	Modified residue	50	1	N6-acetyllysine Ref.9
	Modified residue	154	1	N6-acetyllysine Ref.9
Natural variations
	Alternative sequence	1 – 61	61	Missing in isoform 3.		VSP_012208
	Alternative sequence	48 – 163	116	Missing in isoform 4.		VSP_043343
	Alternative sequence	79 – 94	16	Missing in isoform 2.		VSP_012209
	Natural variant	70	1	T → S. Ref.4 Corresponds to variant rs8191611 [ dbSNP | Ensembl ].		VAR_020585
	Natural variant	103	1	R → Q. Ref.1 Ref.4 Corresponds to variant rs8191613 [ dbSNP | Ensembl ].		VAR_020586
	Natural variant	103	1	R → W. Ref.4 Corresponds to variant rs8191612 [ dbSNP | Ensembl ].		VAR_020587
	Natural variant	257	1	R → L. Ref.4 Corresponds to variant rs8191664 [ dbSNP | Ensembl ].		VAR_020588
	Natural variant	304	1	P → T. Ref.4 Corresponds to variant rs8191666 [ dbSNP | Ensembl ].		VAR_020589
Experimental info
	Mutagenesis	50	1	K → R: Loss of glycosylase and AP lyase activity. Ref.8 Ref.9
	Mutagenesis	154	1	K → R: No effect on glycosylase and AP lyase activity. Ref.9
	Mutagenesis	291	1	C → S: Loss of glycosylase and AP lyase activity. Ref.10
	Mutagenesis	295	1	H → A: Loss of glycosylase and AP lyase activity. Ref.10
	Mutagenesis	310	1	R → Q: Strongly reduces strand AP lyase activity. Ref.10
	Mutagenesis	315	1	C → S: Loss of glycosylase and AP lyase activity. Ref.10
	Mutagenesis	318	1	C → S: Loss of glycosylase and AP lyase activity. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 8A8E76B75ABADE6D	FASTA	332	36,826
	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
	Isoform 2 [UniParc]. Checksum: 3183DDC0C41936DC	FASTA	316	35,247
	10 20 30 40 50 60 MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVHGK KLFLRFDLDE 70 80 90 100 110 120 EMGPPGSSPT PEPPQKEVQK TLDGSSRSAE LVPQGEDDSE YLERDAPAGD AGRWLRVSFG 130 140 150 160 170 180 LFGSVWVNDF SRAKKANKRG DWRDPSPRLV LHFGGGGFLA FYNCQLSWSS SPVVTPTCDI 190 200 210 220 230 240 LSEKFHRGQA LEALGQAQPV CYTLLDQRYF SGLGNIIKNE ALYRAGIHPL SLGSVLSASR 250 260 270 280 290 300 REVLVDHVVE FSTAWLQGKF QGRPQHTQVY QKEQCPAGHQ VMKEAFGPED GLQRLTWWCP 310 QCQPQLSEEP EQCQFS
	Isoform 3 [UniParc]. Checksum: A23E2B89F5256AE6	FASTA	271	29,930
	10 20 30 40 50 60 MGPPGSSPTP EPPQKEVQKE GAADPKQVGE PSGQKTLDGS SRSAELVPQG EDDSEYLERD 70 80 90 100 110 120 APAGDAGRWL RVSFGLFGSV WVNDFSRAKK ANKRGDWRDP SPRLVLHFGG GGFLAFYNCQ 130 140 150 160 170 180 LSWSSSPVVT PTCDILSEKF HRGQALEALG QAQPVCYTLL DQRYFSGLGN IIKNEALYRA 190 200 210 220 230 240 GIHPLSLGSV LSASRREVLV DHVVEFSTAW LQGKFQGRPQ HTQVYQKEQC PAGHQVMKEA 250 260 270 FGPEDGLQRL TWWCPQCQPQ LSEEPEQCQF S
	Isoform 4 [UniParc]. Checksum: 250E84C5B5DAF3CB	FASTA	216	24,136
	10 20 30 40 50 60 MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVRLV LHFGGGGFLA 70 80 90 100 110 120 FYNCQLSWSS SPVVTPTCDI LSEKFHRGQA LEALGQAQPV CYTLLDQRYF SGLGNIIKNE 130 140 150 160 170 180 ALYRAGIHPL SLGSVLSASR REVLVDHVVE FSTAWLQGKF QGRPQHTQVY QKEQCPAGHQ 190 200 210 VMKEAFGPED GLQRLTWWCP QCQPQLSEEP EQCQFS

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] (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. , 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. , 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, MASS SPECTROMETRY, 3D-STRUCTURE MODELING OF 192-319.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

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.

IPI

IPI00410616.
IPI00478031.
IPI00478436.

RefSeq

NP_001129218.1. NM_001135746.1.
NP_001129219.1. NM_001135747.1.
NP_001129220.1. NM_001135748.1.
NP_659480.1. NM_145043.2.

UniGene

Hs.293818.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VZP	model	-	A	192-319	[»]

ProteinModelPortal

Q969S2.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000284503.

PTM databases

PhosphoSite

Q969S2.

Polymorphism databases

DMDM

56404653.

Proteomic databases

PaxDb

Q969S2.

PRIDE

Q969S2.

Protocols and materials databases

DNASU

252969.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000284503; ENSP00000284503; ENSG00000154328.
ENST00000403422; ENSP00000384070; ENSG00000154328.
ENST00000436750; ENSP00000394023; ENSG00000154328.
ENST00000455213; ENSP00000397538; ENSG00000154328.
ENST00000528323; ENSP00000435657; ENSG00000154328.

GeneID

252969.

KEGG

hsa:252969.

UCSC

uc003wue.2. human.

Organism-specific databases

CTD

252969.

GeneCards

GC08P011627.

HGNC

HGNC:18956. NEIL2.

MIM

608933. gene.

neXtProt

NX_Q969S2.

PharmGKB

PA38769.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG73546.

HOGENOM

HOG000069913.

HOVERGEN

HBG082014.

InParanoid

Q969S2.

KO

K10568.

OMA

GHQVMKE.

OrthoDB

EOG4GTKDB.

PhylomeDB

Q969S2.

Gene expression databases

ArrayExpress

Q969S2.

Bgee

Q969S2.

CleanEx

HS_NEIL2.

Genevestigator

Q969S2.

GermOnline

ENSG00000154328. Homo sapiens.

Family and domain databases

InterPro

IPR015886. 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]

Pfam

PF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
[Graphical view]

SUPFAM

SSF46946. Ribosomal_H2TH. 1 hit.

PROSITE

PS51068. FPG_CAT. 1 hit.
PS01242. ZF_FPG_1. False negative.
PS51066. ZF_FPG_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NEIL2. human.

GenomeRNAi

252969.

NextBio

92030.

SOURCE

Search...

Entry information

Entry name

NEIL2_HUMAN

Accession

Primary (citable) accession number: Q969S2
Secondary accession number(s): B4DFR7 , Q7Z3Q7, Q8N842, Q8NG52

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 99 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.