{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9H816","secondaryAccessions":["Q9H9E5"],"uniProtkbId":"DCR1B_HUMAN","entryAudit":{"firstPublicDate":"2005-08-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-03-01","entryVersion":182,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"5' exonuclease Apollo"},"ecNumbers":[{"value":"3.1.-.-"}]},"alternativeNames":[{"fullName":{"value":"Beta-lactamase DCLRE1B"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31434986"}],"value":"3.5.2.6"}]},{"fullName":{"value":"DNA cross-link repair 1B protein"}},{"fullName":{"value":"SNM1 homolog B"},"shortNames":[{"value":"SNMIB"},{"value":"hSNM1B"}]}]},"genes":[{"geneName":{"value":"DCLRE1B"},"synonyms":[{"value":"SNM1B"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15467758"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15572677"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18468965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18469862"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19197158"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19411856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20655466"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31434986"}],"value":"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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a beta-lactam + H2O = a substituted beta-amino acid","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:20401"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:35627"},{"database":"ChEBI","id":"CHEBI:140347"}],"ecNumber":"3.5.2.6","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31434986"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31434986"}],"value":"Beta-lactamase activity is inhibited by sulbactam"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16606622"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18202258"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18468965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18469862"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593705"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19197158"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19411856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20655466"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}],"value":"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)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P02649","geneName":"APOE","intActId":"EBI-1222467"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P54252","geneName":"ATXN3","intActId":"EBI-946046"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P21964-2","geneName":"COMT","intActId":"EBI-10200977"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P50570-2","geneName":"DNM2","intActId":"EBI-10968534"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P26378-2","geneName":"ELAVL4","intActId":"EBI-21603100"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P42858","geneName":"HTT","intActId":"EBI-466029"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"Q92597","geneName":"NDRG1","intActId":"EBI-716486"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"Q86UR1-2","geneName":"NOXA1","intActId":"EBI-12025760"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"P49768-2","geneName":"PSEN1","intActId":"EBI-11047108"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"Q7Z699","geneName":"SPRED1","intActId":"EBI-5235340"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"Q9NUW8","geneName":"TDP1","intActId":"EBI-2902553"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"Q15554","geneName":"TERF2","intActId":"EBI-706637"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9H816","intActId":"EBI-3508943"},"interactantTwo":{"uniProtKBAccession":"O76024","geneName":"WFS1","intActId":"EBI-720609"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"value":"Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome"}]},"subcellularLocations":[{"location":{"value":"Chromosome, telomere","id":"SL-0276"}},{"location":{"value":"Nucleus","id":"SL-0191"}},{"location":{"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","id":"SL-0048"}}]},{"texts":[{"value":"The TBM domain mediates interaction with TERF2"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593705"}],"value":"Ubiquitinated, leading to its degradation. Interaction with TERF2 protects it from ubiquitination"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Dyskeratosis congenita, autosomal recessive, 8","diseaseAccession":"DI-06549","acronym":"DKCB8","description":"A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. 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DKCB8 patients exhibit normal global telemore length, although there is evidence of telomere instability.","diseaseCrossReference":{"database":"MIM","id":"620133"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20479256"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20479256"}],"value":"The disease is caused by variants affecting the gene represented in this entry. In addition to missense and stop-gain variants, an aberrant splice variant of DCLRE1B, designated Apollo-Delta, has been found in a patient with severe dyskeratosis congenita and features of Hoyeraal-Hreidarsson syndrome (PubMed:20479256). Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome"}]}},{"texts":[{"value":"Was named 'Apollo' in reference to the twin brother of 'Artemis' in Greek mythology (PubMed:16730175, PubMed:16730176). Artemis/DCLRE1C is a related nuclease"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAB14284.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":532,"modifier":"EXACT"}},"description":"5' exonuclease Apollo","featureId":"PRO_0000209119"},{"type":"Region","location":{"start":{"value":350,"modifier":"EXACT"},"end":{"value":392,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":453,"modifier":"EXACT"},"end":{"value":482,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Motif","location":{"start":{"value":496,"modifier":"EXACT"},"end":{"value":511,"modifier":"EXACT"}},"description":"TBM"},{"type":"Cross-link","location":{"start":{"value":333,"modifier":"EXACT"},"end":{"value":333,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"28112733"}]},{"type":"Natural variant","location":{"start":{"value":46,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"in dbSNP:rs28381069","featureCrossReferences":[{"database":"dbSNP","id":"rs28381069"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.2"}],"featureId":"VAR_023292","alternativeSequence":{"originalSequence":"R","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":61,"modifier":"EXACT"},"end":{"value":61,"modifier":"EXACT"}},"description":"in dbSNP:rs11552449","featureCrossReferences":[{"database":"dbSNP","id":"rs11552449"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.2"}],"featureId":"VAR_023293","alternativeSequence":{"originalSequence":"H","alternativeSequences":["Y"]}},{"type":"Natural variant","location":{"start":{"value":122,"modifier":"EXACT"},"end":{"value":532,"modifier":"EXACT"}},"description":"in DKCB8","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}],"featureId":"VAR_087866","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"in DKCB8; decreased interaction with TERF2","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}],"featureId":"VAR_087867","alternativeSequence":{"originalSequence":"L","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":142,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"in DKCB8; decreased interaction with TERF2; dbSNP:rs763252884","featureCrossReferences":[{"database":"dbSNP","id":"rs763252884"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}],"featureId":"VAR_087868","alternativeSequence":{"originalSequence":"L","alternativeSequences":["S"]}},{"type":"Natural variant","location":{"start":{"value":158,"modifier":"EXACT"},"end":{"value":532,"modifier":"EXACT"}},"description":"in DKCB8","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35007328"}],"featureId":"VAR_087869","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":462,"modifier":"EXACT"},"end":{"value":462,"modifier":"EXACT"}},"description":"in dbSNP:rs28381079","featureCrossReferences":[{"database":"dbSNP","id":"rs28381079"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.2"}],"featureId":"VAR_023294","alternativeSequence":{"originalSequence":"D","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":510,"modifier":"EXACT"},"end":{"value":510,"modifier":"EXACT"}},"description":"in dbSNP:rs35397235","featureCrossReferences":[{"database":"dbSNP","id":"rs35397235"}],"featureId":"VAR_048891","alternativeSequence":{"originalSequence":"N","alternativeSequences":["Y"]}},{"type":"Mutagenesis","location":{"start":{"value":14,"modifier":"EXACT"},"end":{"value":14,"modifier":"EXACT"}},"description":"In Apm3; abolishes exonuclease activity and function on telomere maintenance. 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