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Reviewed, UniProtKB/Swiss-Prot Q96FI4 (NEIL1_HUMAN)

Last modified June 16, 2009. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Endonuclease VIII-like 1
      Short name=Nei-like 1
    EC=3.2.2.-
    EC=4.2.99.18
Alternative name(s):
    DNA glycosylase/AP lyase Neil1
    DNA-(apurinic or apyrimidinic site) lyase Neil1
    NEH1
    FPG1
Gene names
Name: NEIL1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length390 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. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 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. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Ref.1 Ref.5 Ref.6 Ref.7

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.

Tissue specificity

Ubiquitous. Ref.6

Induction

Up-regulated during S-phase. Ref.6

Sequence similarities

Belongs to the FPG family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96FI4-1)

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: Q96FI4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     75-139: LVFRFGMSGS...QPGRGPCVLQ → PRGAATPCPP...QGECATKPSG
     140-390: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 390389Endonuclease VIII-like 1
PRO_0000170905

Sites

Active site21Schiff-base intermediate with DNA Probable
Active site31Proton donor Probable
Active site541Proton donor; for beta-elimination activity Probable
Active site3391Proton donor; for delta-elimination activity Probable
Binding site1761DNA By similarity
Binding site3391DNA By similarity

Natural variations

Alternative sequence75 – 13965LVFRF…PCVLQ → PRGAATPCPPALLHGPAWPP ARPMFRGHPPVRPLGPWGKV AAGPRALCLAGVPAVQGECA TKPSG in isoform 2.
VSP_012205
Alternative sequence140 – 390251Missing in isoform 2.
VSP_012206
Natural variant821S → C in dnSNP:5745905. Ref.3
VAR_020580
Natural variant831G → D in dnSNP:5745906. Ref.3
VAR_020581
Natural variant1361C → R in dnSNP:5745907. Ref.3
VAR_020582
Natural variant1821I → M in dnSNP:7183491.
VAR_020583
Natural variant2521D → N: dbSNP rs5745926. Ref.3
VAR_020584

Experimental info

Mutagenesis21P → T: Loss of glycosylase and AP lyase activity. Ref.5 Ref.6
Mutagenesis21Missing: Loss of glycosylase activity. Ref.5 Ref.6
Mutagenesis31E → Q: Loss of glycosylase and AP lyase activity. Ref.5
Mutagenesis541K → L: Loss of glycosylase activity. Ref.7
Mutagenesis2771R → A: Strongly reduced glycosylase activity. Has little effect on AP lyase activity. Ref.8
Sequence conflict1471N → S in BAB15337. Ref.2
Sequence conflict2421K → R in BAC06476. Ref.1
Sequence conflict2421K → R in BAB15337. Ref.2
Sequence conflict2421K → R in AAH10876. Ref.4

Secondary structure

................................................... 390
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2007. Version 3.
Checksum: B2B058486C4EF835

FASTA39043,684
        10         20         30         40         50         60 
MPEGPELHLA SQFVNEACRA LVFGGCVEKS SVSRNPEVPF ESSAYRISAS ARGKELRLIL 

        70         80         90        100        110        120 
SPLPGAQPQQ EPLALVFRFG MSGSFQLVPR EELPRHAHLR FYTAPPGPRL ALCFVDIRRF 

       130        140        150        160        170        180 
GRWDLGGKWQ PGRGPCVLQE YQQFRENVLR NLADKAFDRP ICEALLDQRF FNGIGNYLRA 

       190        200        210        220        230        240 
EILYRLKIPP FEKARSVLEA LQQHRPSPEL TLSQKIRTKL QNPDLLELCH SVPKEVVQLG 

       250        260        270        280        290        300 
GKGYGSESGE EDFAAFRAWL RCYGMPGMSS LQDRHGRTIW FQGDPGPLAP KGRKSRKKKS 

       310        320        330        340        350        360 
KATQLSPEDR VEDALPPSKA PSRTRRAKRD LPKRTATQRP EGTSLQQDPE APTVPKKGRR 

       370        380        390 
KGRQAASGHC RPRKVKADIP SLEPEGTSAS 

« Hide

Isoform 2.

Checksum: A5F4799A7C37471D
Show »

FASTA13914,483

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: 12200441] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
Tissue: Testis.
[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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[3]NIEHS SNPs program
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-82; ASP-83; ARG-136 AND ASN-252.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[5]"A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII."
Bandaru V., Sunkara S., Wallace S.S., Bond J.P.
DNA Repair 1:517-529(2002) [PubMed: 12509226] [Abstract]
Cited for: MUTAGENESIS OF PRO-2 AND GLU-3, FUNCTION.
[6]"Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA."
Hazra T.K., Izumi T., Boldogh I., Imhoff B., Kow Y.W., Jaruga P., Dizdaroglu M., Mitra S.
Proc. Natl. Acad. Sci. U.S.A. 99:3523-3528(2002) [PubMed: 11904416] [Abstract]
Cited for: MUTAGENESIS OF PRO-2, FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[7]"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: 14522990] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-54.
[8]"The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity."
Doublie S., Bandaru V., Bond J.P., Wallace S.S.
Proc. Natl. Acad. Sci. U.S.A. 101:10284-10289(2004) [PubMed: 15232006] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-334, MUTAGENESIS OF ARG-277.
+Additional computationally mapped references.

Cross-references

Sequence databases

AB079068 mRNA. Translation: BAC06476.1.
AK026055 mRNA. Translation: BAB15337.1.
AK128372 mRNA. No translation available.
AY257544 Genomic DNA. Translation: AAO74826.1.
BC010876 mRNA. Translation: AAH10876.1.
IPIIPI00305213.
IPI00746550.
RefSeqNP_078884.2.
UniGeneHs.512732

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1TDHX-ray2.10A1-390[»]
ModBaseSearch...

PTM databases

PhosphoSiteQ96FI4.

Proteomic databases

PRIDEQ96FI4.

Genome annotation databases

EnsemblENSG00000140398. Homo sapiens. [Contig view]
GeneID79661.
KEGGhsa:79661.

Organism-specific databases

GeneCardsGC15P073426.
H-InvDBHIX0012440.
HGNCHGNC:18448. NEIL1.
MIM608844. gene.
PharmGKBPA38334.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ96FI4.
HOVERGENQ96FI4.
OMAQ96FI4. WFQGDPG.

Enzyme and pathway databases

BRENDA3.2.2.23. 247.
4.2.99.18. 247.

Gene expression databases

BgeeQ96FI4.
CleanExHS_NEIL1.
GermOnlineENSG00000140398. Homo sapiens.

Family and domain databases

InterProIPR015886. DNA_glyclase/AP_lyase_DNA-bd.
IPR012319. DNA_glycosylase/AP_lyase_cat.
IPR015371. Endonuclease-VIII_DNA_bd.
[Graphical view]
PfamPF01149. Fapy_DNA_glyco. 1 hit.
PF06831. H2TH. 1 hit.
PF09292. Neil1-DNA_bind. 1 hit.
[Graphical view]
ProDomPD003680. Fapy_DNA_glyco. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS51068. FPG_CAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio68852.
SOURCESearch...

Entry information

Entry nameNEIL1_HUMAN
AccessionPrimary (citable) accession number: Q96FI4
Secondary accession number(s): Q6ZRA7, Q86XW7, Q9H6C3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: January 23, 2007
Last modified: June 16, 2009
This is version 74 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents