UniProtKB - Q9H816 (DCR1B_HUMAN)
5' exonuclease Apollo
DCLRE1B
Functioni
5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (PubMed:31434986).
Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (PubMed:31434986).
10 PublicationsMiscellaneous
Catalytic activityi
- EC:3.5.2.61 Publication
Activity regulationi
GO - Molecular functioni
- 5'-3' exodeoxyribonuclease activity Source: GO_Central
- 5'-3' exonuclease activity Source: UniProtKB
- beta-lactamase activity Source: UniProtKB
- damaged DNA binding Source: GO_Central
- protein-containing complex binding Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
GO - Biological processi
- double-strand break repair via nonhomologous end joining Source: GO_Central
- interstrand cross-link repair Source: BHF-UCL
- protection from non-homologous end joining at telomere Source: UniProtKB
- telomere capping Source: BHF-UCL
- telomere maintenance Source: UniProtKB
- telomere maintenance via telomere lengthening Source: BHF-UCL
- telomeric 3' overhang formation Source: UniProtKB
- telomeric loop formation Source: UniProtKB
Keywordsi
Molecular function | Exonuclease, Hydrolase, Nuclease |
Biological process | DNA damage, DNA repair |
Enzyme and pathway databases
PathwayCommonsi | Q9H816 |
Reactomei | R-HSA-6783310, Fanconi Anemia Pathway |
SignaLinki | Q9H816 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:DCLRE1B Synonyms:SNM1B |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17641, DCLRE1B |
MIMi | 609683, gene |
neXtProti | NX_Q9H816 |
VEuPathDBi | HostDB:ENSG00000118655 |
Subcellular locationi
Cytoskeleton
Nucleus
Other locations
Note: Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome.
Cytoskeleton
- centrosome Source: UniProtKB
Nucleus
- nuclear body Source: HPA
- nucleoplasm Source: HPA
Other locations
- chromosome, telomeric region Source: UniProtKB
- cytoplasm Source: UniProtKB-KW
Keywords - Cellular componenti
Chromosome, Cytoplasm, Cytoskeleton, Nucleus, TelomerePathology & Biotechi
Involvement in diseasei
Hoyeraal-Hreidarsson syndrome (HHS)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 14 | D → N in Apm3; abolishes exonuclease activity and function on telomere maintenance. Impairs interaction with SPAG5. 2 Publications | 1 | |
Mutagenesisi | 33 | H → A in Apm1; abolishes exonuclease activity and function on telomere maintenance; when associated with N-35. 1 Publication | 1 | |
Mutagenesisi | 35 | D → N in Apm2; abolishes exonuclease activity and function on telomere maintenance. In Apm1; abolishes exonuclease activity and function on telomere maintenance; when associated with A-33. 1 Publication | 1 | |
Mutagenesisi | 276 | H → A: Slightly affects interaction with SPAG5. 1 Publication | 1 | |
Mutagenesisi | 504 | Y → A: Abolishes interaction with TERF2. 1 Publication | 1 | |
Mutagenesisi | 506 | L → A: Abolishes interaction with TERF2. 1 Publication | 1 | |
Mutagenesisi | 508 | P → A: Abolishes interaction with TERF2. 1 Publication | 1 |
Keywords - Diseasei
Dyskeratosis congenitaOrganism-specific databases
DisGeNETi | 64858 |
MIMi | 305000, phenotype |
OpenTargetsi | ENSG00000118655 |
PharmGKBi | PA27175 |
Miscellaneous databases
Pharosi | Q9H816, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105944 |
Genetic variation databases
BioMutai | DCLRE1B |
DMDMi | 73620756 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000209119 | 1 – 532 | 5' exonuclease ApolloAdd BLAST | 532 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 333 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Ubl conjugationProteomic databases
EPDi | Q9H816 |
MassIVEi | Q9H816 |
PaxDbi | Q9H816 |
PeptideAtlasi | Q9H816 |
PRIDEi | Q9H816 |
ProteomicsDBi | 81169 |
PTM databases
iPTMneti | Q9H816 |
PhosphoSitePlusi | Q9H816 |
Expressioni
Gene expression databases
Bgeei | ENSG00000118655, Expressed in secondary oocyte and 188 other tissues |
ExpressionAtlasi | Q9H816, baseline and differential |
Genevisiblei | Q9H816, HS |
Organism-specific databases
HPAi | ENSG00000118655, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with TERF2; the interaction is direct.
Interacts with MUS81, MRE11 and FANCD2.
Interacts with HSPA2, HSPA8 and HSPA14.
Interacts with SPAG5.
10 PublicationsBinary interactionsi
Q9H816
GO - Molecular functioni
- protein homodimerization activity Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 122331, 30 interactors |
DIPi | DIP-42669N |
ELMi | Q9H816 |
IntActi | Q9H816, 31 interactors |
MINTi | Q9H816 |
STRINGi | 9606.ENSP00000358576 |
Chemistry databases
BindingDBi | Q9H816 |
Miscellaneous databases
RNActi | Q9H816, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q9H816 |
SMRi | Q9H816 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9H816 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 350 – 392 | DisorderedSequence analysisAdd BLAST | 43 | |
Regioni | 453 – 482 | DisorderedSequence analysisAdd BLAST | 30 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 496 – 511 | TBMAdd BLAST | 16 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 361 – 392 | Basic and acidic residuesSequence analysisAdd BLAST | 32 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1361, Eukaryota |
GeneTreei | ENSGT00940000158175 |
HOGENOMi | CLU_034741_0_0_1 |
OMAi | KMVTVLT |
OrthoDBi | 1441774at2759 |
PhylomeDBi | Q9H816 |
TreeFami | TF329572 |
Family and domain databases
DisProti | DP01268 |
Gene3Di | 3.60.15.10, 1 hit |
IDEALi | IID00116 |
InterProi | View protein in InterPro IPR011084, DRMBL IPR036866, RibonucZ/Hydroxyglut_hydro |
Pfami | View protein in Pfam PF07522, DRMBL, 1 hit |
SUPFAMi | SSF56281, SSF56281, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MNGVLIPHTP IAVDFWSLRR AGTARLFFLS HMHSDHTVGL SSTWARPLYC
60 70 80 90 100
SPITAHLLHR HLQVSKQWIQ ALEVGESHVL PLDEIGQETM TVTLLDANHC
110 120 130 140 150
PGSVMFLFEG YFGTILYTGD FRYTPSMLKE PALTLGKQIH TLYLDNTNCN
160 170 180 190 200
PALVLPSRQE AAHQIVQLIR KHPQHNIKIG LYSLGKESLL EQLALEFQTW
210 220 230 240 250
VVLSPRRLEL VQLLGLADVF TVEEKAGRIH AVDHMEICHS NMLRWNQTHP
260 270 280 290 300
TIAILPTSRK IHSSHPDIHV IPYSDHSSYS ELRAFVAALK PCQVVPIVSR
310 320 330 340 350
RPCGGFQDSL SPRISVPLIP DSVQQYMSSS SRKPSLLWLL ERRLKRPRTQ
360 370 380 390 400
GVVFESPEES ADQSQADRDS KKAKKEKLSP WPADLEKQPS HHPLRIKKQL
410 420 430 440 450
FPDLYSKEWN KAVPFCESQK RVTMLTAPLG FSVHLRSTDE EFISQKTREE
460 470 480 490 500
IGLGSPLVPM GDDDGGPEAT GNQSAWMGHG SPLSHSSKGT PLLATEFRGL
510 520 530
ALKYLLTPVN FFQAGYSSRR FDQQVEKYHK PC
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A3B3ITQ0 | A0A3B3ITQ0_HUMAN | 5' exonuclease Apollo | DCLRE1B | 471 | Annotation score: | ||
A0A3B3IT16 | A0A3B3IT16_HUMAN | 5' exonuclease Apollo | DCLRE1B | 72 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 237 | I → T in BAB14284 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023292 | 46 | R → L1 PublicationCorresponds to variant dbSNP:rs28381069EnsemblClinVar. | 1 | |
Natural variantiVAR_023293 | 61 | H → Y1 PublicationCorresponds to variant dbSNP:rs11552449EnsemblClinVar. | 1 | |
Natural variantiVAR_023294 | 462 | D → N1 PublicationCorresponds to variant dbSNP:rs28381079EnsemblClinVar. | 1 | |
Natural variantiVAR_048891 | 510 | N → Y. Corresponds to variant dbSNP:rs35397235EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK022872 mRNA Translation: BAB14284.1 Different initiation. AK024060 mRNA Translation: BAB14807.1 AY849379 Genomic DNA Translation: AAV97812.1 AL137856 Genomic DNA No translation available. BC029687 mRNA Translation: AAH29687.1 |
CCDSi | CCDS866.1 |
RefSeqi | NP_001306876.1, NM_001319947.1 NP_073747.1, NM_022836.3 |
Genome annotation databases
Ensembli | ENST00000650450.2; ENSP00000498042.1; ENSG00000118655.7 |
GeneIDi | 64858 |
KEGGi | hsa:64858 |
MANE-Selecti | ENST00000650450.2; ENSP00000498042.1; NM_022836.4; NP_073747.1 |
UCSCi | uc001eeg.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK022872 mRNA Translation: BAB14284.1 Different initiation. AK024060 mRNA Translation: BAB14807.1 AY849379 Genomic DNA Translation: AAV97812.1 AL137856 Genomic DNA No translation available. BC029687 mRNA Translation: AAH29687.1 |
CCDSi | CCDS866.1 |
RefSeqi | NP_001306876.1, NM_001319947.1 NP_073747.1, NM_022836.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3BUA | X-ray | 2.50 | E/F/G/H | 495-530 | [»] | |
5AHO | X-ray | 2.16 | A | 1-335 | [»] | |
7A1F | X-ray | 1.80 | A/L | 1-335 | [»] | |
7B2X | X-ray | 3.10 | A | 2-335 | [»] | |
7B9B | X-ray | 2.80 | A | 1-335 | [»] | |
AlphaFoldDBi | Q9H816 | |||||
SMRi | Q9H816 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 122331, 30 interactors |
DIPi | DIP-42669N |
ELMi | Q9H816 |
IntActi | Q9H816, 31 interactors |
MINTi | Q9H816 |
STRINGi | 9606.ENSP00000358576 |
Chemistry databases
BindingDBi | Q9H816 |
ChEMBLi | CHEMBL4105944 |
PTM databases
iPTMneti | Q9H816 |
PhosphoSitePlusi | Q9H816 |
Genetic variation databases
BioMutai | DCLRE1B |
DMDMi | 73620756 |
Proteomic databases
EPDi | Q9H816 |
MassIVEi | Q9H816 |
PaxDbi | Q9H816 |
PeptideAtlasi | Q9H816 |
PRIDEi | Q9H816 |
ProteomicsDBi | 81169 |
Protocols and materials databases
Antibodypediai | 46943, 158 antibodies from 24 providers |
DNASUi | 64858 |
Genome annotation databases
Ensembli | ENST00000650450.2; ENSP00000498042.1; ENSG00000118655.7 |
GeneIDi | 64858 |
KEGGi | hsa:64858 |
MANE-Selecti | ENST00000650450.2; ENSP00000498042.1; NM_022836.4; NP_073747.1 |
UCSCi | uc001eeg.4, human |
Organism-specific databases
CTDi | 64858 |
DisGeNETi | 64858 |
GeneCardsi | DCLRE1B |
HGNCi | HGNC:17641, DCLRE1B |
HPAi | ENSG00000118655, Low tissue specificity |
MIMi | 305000, phenotype 609683, gene |
neXtProti | NX_Q9H816 |
OpenTargetsi | ENSG00000118655 |
PharmGKBi | PA27175 |
VEuPathDBi | HostDB:ENSG00000118655 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1361, Eukaryota |
GeneTreei | ENSGT00940000158175 |
HOGENOMi | CLU_034741_0_0_1 |
OMAi | KMVTVLT |
OrthoDBi | 1441774at2759 |
PhylomeDBi | Q9H816 |
TreeFami | TF329572 |
Enzyme and pathway databases
PathwayCommonsi | Q9H816 |
Reactomei | R-HSA-6783310, Fanconi Anemia Pathway |
SignaLinki | Q9H816 |
Miscellaneous databases
BioGRID-ORCSi | 64858, 422 hits in 1102 CRISPR screens |
ChiTaRSi | DCLRE1B, human |
EvolutionaryTracei | Q9H816 |
GeneWikii | DCLRE1B |
GenomeRNAii | 64858 |
Pharosi | Q9H816, Tbio |
PROi | PR:Q9H816 |
RNActi | Q9H816, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000118655, Expressed in secondary oocyte and 188 other tissues |
ExpressionAtlasi | Q9H816, baseline and differential |
Genevisiblei | Q9H816, HS |
Family and domain databases
DisProti | DP01268 |
Gene3Di | 3.60.15.10, 1 hit |
IDEALi | IID00116 |
InterProi | View protein in InterPro IPR011084, DRMBL IPR036866, RibonucZ/Hydroxyglut_hydro |
Pfami | View protein in Pfam PF07522, DRMBL, 1 hit |
SUPFAMi | SSF56281, SSF56281, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DCR1B_HUMAN | |
Accessioni | Q9H816Primary (citable) accession number: Q9H816 Secondary accession number(s): Q9H9E5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 16, 2005 |
Last sequence update: | March 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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