Q9H816 · DCR1B_HUMAN
- Protein5' exonuclease Apollo
- GeneDCLRE1B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids532 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (PubMed:31434986).
Miscellaneous
Was named 'Apollo' in reference to the twin brother of 'Artemis' in Greek mythology (PubMed:16730175, PubMed:16730176).
Artemis/DCLRE1C is a related nuclease
Artemis/DCLRE1C is a related nuclease
Catalytic activity
- a beta-lactam + H2O = a substituted beta-amino acid
Activity regulation
Beta-lactamase activity is inhibited by sulbactam.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centrosome | |
Cellular Component | chromosome, telomeric region | |
Cellular Component | cytoplasm | |
Cellular Component | nuclear body | |
Cellular Component | nucleoplasm | |
Molecular Function | 5'-3' DNA exonuclease activity | |
Molecular Function | 5'-3' exonuclease activity | |
Molecular Function | beta-lactamase activity | |
Molecular Function | damaged DNA binding | |
Molecular Function | protein homodimerization activity | |
Molecular Function | protein-containing complex binding | |
Biological Process | double-strand break repair via nonhomologous end joining | |
Biological Process | interstrand cross-link repair | |
Biological Process | protection from non-homologous end joining at telomere | |
Biological Process | telomere capping | |
Biological Process | telomere maintenance | |
Biological Process | telomere maintenance via telomere lengthening | |
Biological Process | telomeric 3' overhang formation | |
Biological Process | telomeric loop formation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name5' exonuclease Apollo
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H816
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Dyskeratosis congenita, autosomal recessive, 8 (DKCB8)
- Note
- DescriptionA form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. Additional DKCB8 features include microcephaly, intrauterine growth retardation, and developmental anomalies in some patients. DKCB8 patients exhibit normal global telemore length, although there is evidence of telomere instability.
- See alsoMIM:620133
Natural variants in DKCB8
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087866 | 122-532 | missing | in DKCB8 | |
VAR_087867 | 142 | L>F | in DKCB8; decreased interaction with TERF2 | |
VAR_087868 | 142 | L>S | in DKCB8; decreased interaction with TERF2; dbSNP:rs763252884 | |
VAR_087869 | 158-532 | missing | in DKCB8 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 14 | In Apm3; abolishes exonuclease activity and function on telomere maintenance. Impairs interaction with SPAG5. | ||||
Sequence: D → N | ||||||
Mutagenesis | 33 | In Apm1; abolishes exonuclease activity and function on telomere maintenance; when associated with N-35. | ||||
Sequence: H → A | ||||||
Mutagenesis | 35 | 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. | ||||
Sequence: D → N | ||||||
Natural variant | VAR_023292 | 46 | in dbSNP:rs28381069 | |||
Sequence: R → L | ||||||
Natural variant | VAR_023293 | 61 | in dbSNP:rs11552449 | |||
Sequence: H → Y | ||||||
Natural variant | VAR_087866 | 122-532 | in DKCB8 | |||
Sequence: Missing | ||||||
Natural variant | VAR_087867 | 142 | in DKCB8; decreased interaction with TERF2 | |||
Sequence: L → F | ||||||
Natural variant | VAR_087868 | 142 | in DKCB8; decreased interaction with TERF2; dbSNP:rs763252884 | |||
Sequence: L → S | ||||||
Natural variant | VAR_087869 | 158-532 | in DKCB8 | |||
Sequence: Missing | ||||||
Mutagenesis | 276 | Slightly affects interaction with SPAG5. | ||||
Sequence: H → A | ||||||
Natural variant | VAR_023294 | 462 | in dbSNP:rs28381079 | |||
Sequence: D → N | ||||||
Mutagenesis | 504 | Abolishes interaction with TERF2. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 506 | Abolishes interaction with TERF2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 508 | Abolishes interaction with TERF2. | ||||
Sequence: P → A | ||||||
Natural variant | VAR_048891 | 510 | in dbSNP:rs35397235 | |||
Sequence: N → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 581 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000209119 | 1-532 | UniProt | 5' exonuclease Apollo | |||
Sequence: MNGVLIPHTPIAVDFWSLRRAGTARLFFLSHMHSDHTVGLSSTWARPLYCSPITAHLLHRHLQVSKQWIQALEVGESHVLPLDEIGQETMTVTLLDANHCPGSVMFLFEGYFGTILYTGDFRYTPSMLKEPALTLGKQIHTLYLDNTNCNPALVLPSRQEAAHQIVQLIRKHPQHNIKIGLYSLGKESLLEQLALEFQTWVVLSPRRLELVQLLGLADVFTVEEKAGRIHAVDHMEICHSNMLRWNQTHPTIAILPTSRKIHSSHPDIHVIPYSDHSSYSELRAFVAALKPCQVVPIVSRRPCGGFQDSLSPRISVPLIPDSVQQYMSSSSRKPSLLWLLERRLKRPRTQGVVFESPEESADQSQADRDSKKAKKEKLSPWPADLEKQPSHHPLRIKKQLFPDLYSKEWNKAVPFCESQKRVTMLTAPLGFSVHLRSTDEEFISQKTREEIGLGSPLVPMGDDDGGPEATGNQSAWMGHGSPLSHSSKGTPLLATEFRGLALKYLLTPVNFFQAGYSSRRFDQQVEKYHKPC | |||||||
Cross-link | 333 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 356 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated, leading to its degradation. Interaction with TERF2 protects it from ubiquitination.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with TERF2; the interaction is direct (PubMed:16606622, PubMed:16730175, PubMed:16730176, PubMed:18468965, PubMed:18593705, PubMed:20655466, PubMed:35007328).
Interacts with MUS81, MRE11 and FANCD2 (PubMed:18469862).
Interacts with HSPA2, HSPA8 and HSPA14 (PubMed:19411856).
Interacts with SPAG5 (PubMed:19197158).
Interacts with MUS81, MRE11 and FANCD2 (PubMed:18469862).
Interacts with HSPA2, HSPA8 and HSPA14 (PubMed:19411856).
Interacts with SPAG5 (PubMed:19197158).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9H816 | APOE P02649 | 3 | EBI-3508943, EBI-1222467 | |
BINARY | Q9H816 | ATXN3 P54252 | 3 | EBI-3508943, EBI-946046 | |
BINARY | Q9H816 | COMT P21964-2 | 3 | EBI-3508943, EBI-10200977 | |
BINARY | Q9H816 | DNM2 P50570-2 | 3 | EBI-3508943, EBI-10968534 | |
BINARY | Q9H816 | ELAVL4 P26378-2 | 3 | EBI-3508943, EBI-21603100 | |
BINARY | Q9H816 | HTT P42858 | 9 | EBI-3508943, EBI-466029 | |
BINARY | Q9H816 | NDRG1 Q92597 | 3 | EBI-3508943, EBI-716486 | |
BINARY | Q9H816 | NOXA1 Q86UR1-2 | 3 | EBI-3508943, EBI-12025760 | |
BINARY | Q9H816 | PSEN1 P49768-2 | 3 | EBI-3508943, EBI-11047108 | |
BINARY | Q9H816 | SPRED1 Q7Z699 | 3 | EBI-3508943, EBI-5235340 | |
BINARY | Q9H816 | TDP1 Q9NUW8 | 3 | EBI-3508943, EBI-2902553 | |
BINARY | Q9H816 | TERF2 Q15554 | 11 | EBI-3508943, EBI-706637 | |
BINARY | Q9H816 | WFS1 O76024 | 3 | EBI-3508943, EBI-720609 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 350-392 | Disordered | ||||
Sequence: QGVVFESPEESADQSQADRDSKKAKKEKLSPWPADLEKQPSHH | ||||||
Compositional bias | 361-392 | Basic and acidic residues | ||||
Sequence: ADQSQADRDSKKAKKEKLSPWPADLEKQPSHH | ||||||
Region | 453-482 | Disordered | ||||
Sequence: LGSPLVPMGDDDGGPEATGNQSAWMGHGSP | ||||||
Motif | 496-511 | TBM | ||||
Sequence: EFRGLALKYLLTPVNF |
Domain
The TBM domain mediates interaction with TERF2.
Sequence similarities
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length532
- Mass (Da)60,002
- Last updated2001-03-01 v1
- Checksum601A800CCD43CFDA
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3B3IT16 | A0A3B3IT16_HUMAN | DCLRE1B | 72 | ||
A0A3B3ITQ0 | A0A3B3ITQ0_HUMAN | DCLRE1B | 471 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 237 | in Ref. 1; BAB14284 | ||||
Sequence: I → T | ||||||
Compositional bias | 361-392 | Basic and acidic residues | ||||
Sequence: ADQSQADRDSKKAKKEKLSPWPADLEKQPSHH |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK022872 EMBL· GenBank· DDBJ | BAB14284.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK024060 EMBL· GenBank· DDBJ | BAB14807.1 EMBL· GenBank· DDBJ | mRNA | ||
AY849379 EMBL· GenBank· DDBJ | AAV97812.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL137856 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC029687 EMBL· GenBank· DDBJ | AAH29687.1 EMBL· GenBank· DDBJ | mRNA |