UniProtKB - Q8K203 (NEIL3_MOUSE)
Protein
Endonuclease 8-like 3
Gene
Neil3
Organism
Mus musculus (Mouse)
Status
Functioni
DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). 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 (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). No activity on 8-oxoG detected (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161).By similarity6 Publications
Caution
Was originally thought to be inactive as a glycosylase, but recent reports demonstrate that cleavage of the initiator methionine is essential for catalytic activity.2 Publications
Catalytic activityi
- 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.PROSITE-ProRule annotation5 Publications EC:4.2.99.18
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 2 | Schiff-base intermediate with DNA; via amino nitrogen1 Publication | 1 | |
Sitei | 2 | Important for monofunctional glycosylase activityBy similarity | 1 | |
Sitei | 82 | Required for glycosylase activityBy similarity | 1 | |
Binding sitei | 193 | DNABy similarity | 1 | |
Binding sitei | 272 | DNABy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 248 – 282 | FPG-typePROSITE-ProRule annotationAdd BLAST | 35 | |
Zinc fingeri | 318 – 347 | RanBP2-typePROSITE-ProRule annotationAdd BLAST | 30 | |
Zinc fingeri | 506 – 550 | GRF-type 1Add BLAST | 45 | |
Zinc fingeri | 553 – 596 | GRF-type 2Add BLAST | 44 |
GO - Molecular functioni
- bubble DNA binding Source: UniProtKB
- class I DNA-(apurinic or apyrimidinic site) endonuclease activity Source: UniProtKB-EC
- damaged DNA binding Source: UniProtKB
- DNA-(apurinic or apyrimidinic site) endonuclease activity Source: UniProtKB
- DNA N-glycosylase activity Source: UniProtKB
- double-stranded DNA binding Source: UniProtKB
- MCM complex binding Source: UniProtKB
- single-stranded DNA binding Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- base-excision repair Source: UniProtKB
- interstrand cross-link repair Source: UniProtKB
- nucleotide-excision repair Source: InterPro
Keywordsi
Molecular function | DNA-binding, Glycosidase, Hydrolase, Lyase, Multifunctional enzyme |
Biological process | DNA damage, DNA repair |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-110330, Recognition and association of DNA glycosylase with site containing an affected purine R-MMU-110331, Cleavage of the damaged purine |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Neil3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2384588, Neil3 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Other locations
- Chromosome By similarity
Note: Recruited to replication stress sites via interaction with ubiquitinated CMG helicase.By similarity
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Keywords - Cellular componenti
Chromosome, NucleusPathology & Biotechi
Disruption phenotypei
Perinatal mice show reduced regeneration of neural tissue following ischemic brain damage (stroke), associated with fewer activated microglia and impaired neural stem cell proliferation. Aged mice show deficits in learning and memory, decreased anxiety-like behavior, and changes in hippocampal synapse composition. Otherwise viable and fertile.4 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCurated | |||
ChainiPRO_0000170911 | 2 – 606 | Endonuclease 8-like 3Add BLAST | 605 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 451 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q8K203 |
PaxDbi | Q8K203 |
PeptideAtlasi | Q8K203 |
PRIDEi | Q8K203 |
PTM databases
iPTMneti | Q8K203 |
PhosphoSitePlusi | Q8K203 |
Expressioni
Tissue specificityi
Expressed in testis, thymus, spleen and bone marrow. In young mice, expressed at higher levels in thymocytes than splenocytes. At 12 dpc, abundant in the subventricular zone (SVZ) of the lateral ventricles. At 17.5 dpc and P0, expression is limited to distinct cells in the cortical SVZ, in cells of the secondary matrix, the dentate gyrus migratory route and the dentate gyrus.4 Publications
Developmental stagei
Highly expressed in the developing brain at 12 dpc-13 dpc when neurogenesis starts. Expression decreases during later development and is undetectable in adult brain.2 Publications
Inductioni
By mitogen stimulation in splenocytes, and by hypoxic-ischemic injury in the striatum and hippocampus.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000039396, Expressed in secondary oocyte and 182 other tissues |
ExpressionAtlasi | Q8K203, baseline and differential |
Genevisiblei | Q8K203, MM |
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000041909 |
Miscellaneous databases
RNActi | Q8K203, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8K203 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
The N-terminal region (2-282) contains the glycosylase and lyase activities.
The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.By similarity
Sequence similaritiesi
Belongs to the FPG family.PROSITE-ProRule annotation
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 248 – 282 | FPG-typePROSITE-ProRule annotationAdd BLAST | 35 | |
Zinc fingeri | 318 – 347 | RanBP2-typePROSITE-ProRule annotationAdd BLAST | 30 | |
Zinc fingeri | 506 – 550 | GRF-type 1Add BLAST | 45 | |
Zinc fingeri | 553 – 596 | GRF-type 2Add BLAST | 44 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502QWRN, Eukaryota |
GeneTreei | ENSGT00940000153230 |
HOGENOMi | CLU_482283_0_0_1 |
InParanoidi | Q8K203 |
OMAi | PDLKSCN |
OrthoDBi | 1467835at2759 |
PhylomeDBi | Q8K203 |
TreeFami | TF331502 |
Family and domain databases
Gene3Di | 3.20.190.10, 1 hit |
InterProi | View protein in InterPro IPR015886, DNA_glyclase/AP_lyase_DNA-bd IPR015887, DNA_glyclase_Znf_dom_DNA_BS IPR012319, FPG_cat IPR035937, MutM-like_N-ter IPR010979, Ribosomal_S13-like_H2TH IPR000214, Znf_DNA_glyclase/AP_lyase IPR010666, Znf_GRF IPR001876, Znf_RanBP2 IPR036443, Znf_RanBP2_sf |
Pfami | View protein in Pfam PF06831, H2TH, 1 hit PF06839, zf-GRF, 2 hits PF00641, zf-RanBP, 1 hit |
SMARTi | View protein in SMART SM01232, H2TH, 1 hit SM00547, ZnF_RBZ, 1 hit |
SUPFAMi | SSF46946, SSF46946, 1 hit SSF81624, SSF81624, 1 hit SSF90209, SSF90209, 1 hit |
PROSITEi | View protein in 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 |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8K203-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVEGPGCTLN GEKIRARVLP GQAVTGVRGT ALQSLLGPAM SPAASLADVA
60 70 80 90 100
TSAAPMNAKD SGWKLLRLFN GYVYSGVETL GKELFMYFGP RALRIHFGMK
110 120 130 140 150
GSILINPREG ENRAGASPAL AVQLTRDLIC FYDSSVELRN SVESQQRVRV
160 170 180 190 200
MEELDICSPK FSFSRAESEV KKQGDRMLCD VLLDQRVLPG VGNIIKNEAL
210 220 230 240 250
FDSGLHPAVK VCQLSDKQAC HLVKMTRDFS ILFYRCCKAG SAISKHCKVY
260 270 280 290 300
KRPNCDQCHS KITVCRFGEN SRMTYFCPHC QKENPQCVQV CQLPTRNTEI
310 320 330 340 350
SWTPRGEDCF TDSVARKSEE QWSCVVCTLI NRPSAKACDA CLTTRPLDSV
360 370 380 390 400
LKNRENSIAF NNLVKYPCNN FENTHTEVKI NRKTAFGNTT LVLTDLSNKS
410 420 430 440 450
SALARKKRAN HTIDGESQMF LPTDIGFSDS QHPSKEGINY ITQPSNKVNI
460 470 480 490 500
SPTVCAQSKL FSSAHKKFKP AHTSATELKS YNSGLSNSEL QTNRTRGHHS
510 520 530 540 550
KSDGSPLCKM HHRRCVLRVV RKDGENKGRQ FYACSLPRGA QCGFFEWADL
560 570 580 590 600
SFPFCRHGKR SIMKTVLKIG PNNGKNFFVC PLEKKKQCNF FQWAENGPGM
EIVPGC
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketD3Z1T7 | D3Z1T7_MOUSE | Endonuclease 8-like 3 | Neil3 | 49 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 46 | L → P in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 90 | P → H in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 114 | A → G in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 150 | V → E in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 220 | C → R in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 256 | D → G in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 287 | C → R in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 325 | V → A in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 556 | R → K in strain: Czech II. 1 Publication | 1 | |
Natural varianti | 585 | K → E in strain: Czech II. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_012210 | 212 – 606 | Missing in isoform 2. 1 PublicationAdd BLAST | 395 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB072931 mRNA Translation: BAC22661.1 AK031027 mRNA Translation: BAC27219.1 BC024921 mRNA Translation: AAH24921.1 BC034753 mRNA Translation: AAH34753.1 AB202125 Genomic DNA Translation: BAE16548.1 |
CCDSi | CCDS22305.1 [Q8K203-1] |
RefSeqi | NP_666320.1, NM_146208.2 [Q8K203-1] |
Genome annotation databases
Ensembli | ENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396 [Q8K203-1] |
GeneIDi | 234258 |
KEGGi | mmu:234258 |
UCSCi | uc009lsa.2, mouse [Q8K203-1] uc009lsb.2, mouse [Q8K203-2] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB072931 mRNA Translation: BAC22661.1 AK031027 mRNA Translation: BAC27219.1 BC024921 mRNA Translation: AAH24921.1 BC034753 mRNA Translation: AAH34753.1 AB202125 Genomic DNA Translation: BAE16548.1 |
CCDSi | CCDS22305.1 [Q8K203-1] |
RefSeqi | NP_666320.1, NM_146208.2 [Q8K203-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3W0F | X-ray | 2.00 | A | 2-282 | [»] | |
SMRi | Q8K203 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000041909 |
PTM databases
iPTMneti | Q8K203 |
PhosphoSitePlusi | Q8K203 |
Proteomic databases
EPDi | Q8K203 |
PaxDbi | Q8K203 |
PeptideAtlasi | Q8K203 |
PRIDEi | Q8K203 |
Protocols and materials databases
Antibodypediai | 17262, 173 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000047768; ENSMUSP00000041909; ENSMUSG00000039396 [Q8K203-1] |
GeneIDi | 234258 |
KEGGi | mmu:234258 |
UCSCi | uc009lsa.2, mouse [Q8K203-1] uc009lsb.2, mouse [Q8K203-2] |
Organism-specific databases
CTDi | 55247 |
MGIi | MGI:2384588, Neil3 |
Phylogenomic databases
eggNOGi | ENOG502QWRN, Eukaryota |
GeneTreei | ENSGT00940000153230 |
HOGENOMi | CLU_482283_0_0_1 |
InParanoidi | Q8K203 |
OMAi | PDLKSCN |
OrthoDBi | 1467835at2759 |
PhylomeDBi | Q8K203 |
TreeFami | TF331502 |
Enzyme and pathway databases
Reactomei | R-MMU-110330, Recognition and association of DNA glycosylase with site containing an affected purine R-MMU-110331, Cleavage of the damaged purine |
Miscellaneous databases
BioGRID-ORCSi | 234258, 2 hits in 18 CRISPR screens |
ChiTaRSi | Neil3, mouse |
PROi | PR:Q8K203 |
RNActi | Q8K203, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000039396, Expressed in secondary oocyte and 182 other tissues |
ExpressionAtlasi | Q8K203, baseline and differential |
Genevisiblei | Q8K203, MM |
Family and domain databases
Gene3Di | 3.20.190.10, 1 hit |
InterProi | View protein in InterPro IPR015886, DNA_glyclase/AP_lyase_DNA-bd IPR015887, DNA_glyclase_Znf_dom_DNA_BS IPR012319, FPG_cat IPR035937, MutM-like_N-ter IPR010979, Ribosomal_S13-like_H2TH IPR000214, Znf_DNA_glyclase/AP_lyase IPR010666, Znf_GRF IPR001876, Znf_RanBP2 IPR036443, Znf_RanBP2_sf |
Pfami | View protein in Pfam PF06831, H2TH, 1 hit PF06839, zf-GRF, 2 hits PF00641, zf-RanBP, 1 hit |
SMARTi | View protein in SMART SM01232, H2TH, 1 hit SM00547, ZnF_RBZ, 1 hit |
SUPFAMi | SSF46946, SSF46946, 1 hit SSF81624, SSF81624, 1 hit SSF90209, SSF90209, 1 hit |
PROSITEi | View protein in 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NEIL3_MOUSE | |
Accessioni | Q8K203Primary (citable) accession number: Q8K203 Secondary accession number(s): Q4ADY6, Q8CD85, Q8R3P4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 7, 2004 |
Last sequence update: | October 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 137 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) 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