{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9NSG2","secondaryAccessions":["A6NFP1","B3KU42","Q3KNQ1","Q9H8L5","Q9NVJ0"],"uniProtkbId":"FIRRM_HUMAN","entryAudit":{"firstPublicDate":"2007-03-06","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-10-01","entryVersion":162,"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":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"37347663"}],"value":"FIGNL1-interacting regulator of recombination and mitosis"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"29608566"}],"value":"FIDGETIN-like-1 interacting protein"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"29608566"}],"value":"FLIP"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"34260926"}],"value":"POLO1-associating protein"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"37347663"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:25565"}],"value":"FIRRM"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"34260926"}],"value":"APOLO1"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"37515771"}],"value":"C1orf112"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3TQQ9"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29608566"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37256941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37347663"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37515771"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37556550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38286805"}],"value":"Forms a complex with FIGL1, which regulates DNA double-strand break (DSB) repair via homologous recombination (HR) (PubMed:29608566, PubMed:37256941, PubMed:37347663, PubMed:37515771, PubMed:37556550, PubMed:38286805). The FIGNL1-FIRRM complex is essential for resolution of homologous recombination intermediates in response to DNA interstrand cross-links (ICLs) (PubMed:37256941, PubMed:37347663, PubMed:37515771, PubMed:37556550, PubMed:38286805). The complex regulates HR by promoting disassembly of RAD51 filaments from DNA and chromatin, thereby preventing DNA damage-independent RAD51 loading and persistent DNA accumulation of RAD51 recombinases (PubMed:37256941, PubMed:37347663, PubMed:37515771, PubMed:37556550, PubMed:38286805). It also regulates HR during meiosis by promoting dissociation of DMC1 filaments from DNA (By similarity). Within the complex, provides the ATPase activity to disassemble DMC1 and RAD51 filaments, while FIRRM directly binds single-stranded DNA to facilitate this unloading (PubMed:37556550). Independently of FIRRM, slso acts as a regulator of PLK1 kinase activity at kinetochores that promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities (PubMed:34260926). Phosphorylation of FIRRM by PLK1 negatively regulates its interaction with the phosphatase, PPP1CC, thus creating a negative feedback loop for maintaining proper PLK1 kinase activity during mitosis (PubMed:34260926)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29608566"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37256941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37347663"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37515771"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37556550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38286805"}],"value":"Interacts with FIGNL1; forming the FIGNL1-FIRRM complex, which regulates homologous recombination (PubMed:29608566, PubMed:37256941, PubMed:37347663, PubMed:37515771, PubMed:37556550, PubMed:38286805). Interacts (via its N-terminal region) with PLK1; controls PLK1 kinase activity (PubMed:34260926). Interacts (via the KVVXF motif) with PPP1CC; controls PLK1 kinase activity (PubMed:34260926)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9NSG2","intActId":"EBI-11128910"},"interactantTwo":{"uniProtKBAccession":"Q6PIW4","geneName":"FIGNL1","intActId":"EBI-8468390"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9NSG2","intActId":"EBI-11128910"},"interactantTwo":{"uniProtKBAccession":"Q7Z4N8","geneName":"P4HA3","intActId":"EBI-10181968"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37556550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38286805"}],"value":"Enriched at DNA damage sites (PubMed:37556550, PubMed:38286805). Exhibits cell-cycle-dependent distribution during mitosis. Detected in the nucleus in interphase (PubMed:34260926). Colocalizes with PLK1 to the centromeres in a nearby prometaphase cells (PubMed:34260926). Relocates to the central spindle in anaphase and to the midbody in telophase cells (PubMed:34260926)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37556550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38286805"}],"value":"Chromosome","id":"SL-0468"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Chromosome, centromere, kinetochore","id":"SL-0149"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Chromosome, centromere","id":"SL-0047"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Midbody","id":"SL-0469"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Cytoplasm, cytoskeleton, spindle","id":"SL-0251"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9NSG2-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9NSG2-2"],"sequenceIds":["VSP_023445"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q9NSG2-3"],"sequenceIds":["VSP_023444"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"value":"Phosphorylation at Ser-43 by PLK1 strengthens FIRRM-PLK1 interaction (PubMed:34260926). Phosphorylation at Ser-744 by PLK1 negatively regulates its interaction with PPP1CC (PubMed:34260926)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the FIRRM family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":853,"modifier":"EXACT"}},"description":"FIGNL1-interacting regulator of recombination and mitosis","featureId":"PRO_0000279461"},{"type":"Modified residue","location":{"start":{"value":43,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"Phosphoserine; by PLK1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"},{"evidenceCode":"ECO:0007744","source":"PubMed","id":"23186163"}]},{"type":"Modified residue","location":{"start":{"value":744,"modifier":"EXACT"},"end":{"value":744,"modifier":"EXACT"}},"description":"Phosphoserine; by PLK1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}]},{"type":"Modified residue","location":{"start":{"value":792,"modifier":"EXACT"},"end":{"value":792,"modifier":"EXACT"}},"description":"N6-acetyllysine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"19608861"}]},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":323,"modifier":"EXACT"}},"description":"in isoform 3","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14702039"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"15489334"}],"featureId":"VSP_023444","alternativeSequence":{}},{"type":"Alternative sequence","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":135,"modifier":"EXACT"}},"description":"in isoform 2","evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14702039"}],"featureId":"VSP_023445","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":481,"modifier":"EXACT"},"end":{"value":481,"modifier":"EXACT"}},"description":"in dbSNP:rs2272920","featureCrossReferences":[{"database":"dbSNP","id":"rs2272920"}],"featureId":"VAR_030906","alternativeSequence":{"originalSequence":"A","alternativeSequences":["S"]}},{"type":"Mutagenesis","location":{"start":{"value":43,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"Decreased binding to PLK1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":43,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"Increased binding to PLK1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34260926"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["D"]}},{"type":"Mutagenesis","location":{"start":{"value":461,"modifier":"EXACT"},"end":{"value":463,"modifier":"EXACT"}},"description":"Abolished interaction with FIGNL1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37556550"}],"alternativeSequence":{}},{"type":"Mutagenesis","location":{"start":{"value":744,"modifier":"EXACT"},"end":{"value":744,"modifier":"EXACT"}},"description":"Does not affect binding to PPP1CC. 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LOCATION":1,"ALTERNATIVE PRODUCTS":3,"PTM":1,"SIMILARITY":1},"countByFeatureType":{"Chain":1,"Modified residue":3,"Alternative sequence":2,"Natural variant":1,"Mutagenesis":5,"Sequence conflict":2},"uniParcId":"UPI000006E467"}}