{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9Y297","secondaryAccessions":["B5MD49","Q5W141","Q5W142","Q9Y213"],"uniProtkbId":"FBW1A_HUMAN","entryAudit":{"firstPublicDate":"2001-02-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1999-11-01","entryVersion":239,"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":"F-box/WD repeat-containing protein 1A"}},"alternativeNames":[{"fullName":{"value":"E3RSIkappaB"}},{"fullName":{"value":"Epididymis tissue protein Li 2a"}},{"fullName":{"value":"F-box and WD repeats protein beta-TrCP"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9859996"}],"value":"pIkappaBalpha-E3 receptor subunit"}}]},"genes":[{"geneName":{"value":"BTRC"},"synonyms":[{"value":"BTRCP"},{"value":"FBW1A"},{"value":"FBXW1A"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3ULA2"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10066435"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10497169"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10644755"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10835356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158290"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11238952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11359933"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11994270"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077367"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12791267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12820959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12902344"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14603323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14673179"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14681206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14988407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448698"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15917222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16371461"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16705181"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18354482"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21258371"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017875"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017877"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22087322"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25503564"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25704143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33110214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38225265"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9859996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9990852"}],"value":"Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11158290, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:25503564, PubMed:25704143, PubMed:36608670, PubMed:9859996, PubMed:9990852). Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11158290, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:25503564, PubMed:25704143, PubMed:36608670, PubMed:9859996, PubMed:9990852). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14603323, PubMed:14681206). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:9859996). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). The SCF(FBXW11) complex also regulates NF-kappa-B by mediating ubiquitination of phosphorylated NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to its degradation (PubMed:10835356, PubMed:11158290, PubMed:14673179). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25503564, PubMed:25704143). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. SCF(BTRC) acts as a negative regulator of smoothened signaling by mediating ubiquitination of GLI2 and GLI3 in absence of smoothened, promoting their processing into transcription repressors (PubMed:16705181, PubMed:16371461). Mediates ubiquitination of REST, thereby leading to its proteasomal degradation (PubMed:18354482, PubMed:21258371). SCF(BTRC) mediates the ubiquitination and subsequent proteasomal degradation of KLF4; thereby negatively regulating cell pluripotency maintenance and embryogenesis (By similarity). SCF(BTRC) acts as a regulator of mTORC1 signaling pathway by catalyzing ubiquitination and subsequent proteasomal degradation of phosphorylated DEPTOR, TFE3 and MITF (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:33110214, PubMed:36608670). SCF(BTRC) directs 'Lys-48'-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway (PubMed:38225265)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10835356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158290"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16371461"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16705181"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017875"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017877"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36608670"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9859996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9990852"}],"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3ULA2"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10066435"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10497169"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10644755"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10835356"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10983987"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11238952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11359933"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12037680"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12077367"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12791267"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12820959"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12902344"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14603323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14681206"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14988407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15448698"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15647282"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15917222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17079684"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17574027"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18354482"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18794143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20068069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017875"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017876"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22017877"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22087322"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25503564"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25704143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29420262"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36608670"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38225265"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9990852"}],"value":"Homodimer. Self-associates. Component of the SCF(BTRC) complex formed of CUL1, SKP1, RBX1 and a BTRC dimer (PubMed:10066435, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:36608670, PubMed:9990852). Direct interaction with SKP1 occurs via the F-box domain. Interacts with phosphorylated ubiquitination substrates SMAD3 and SMAD4. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of the 2 serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (PubMed:25503564, PubMed:25704143). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By similarity). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 (By similarity). Interacts with INAVA (PubMed:29420262). Interacts with IL10RA; this interaction leads to IL10RA ubiquitination and subsequent degradation (PubMed:22087322). Interacts with REST (PubMed:18354482). Interacts with KLF4; this interaction leads to KLF4 ubiquitination and subsequent degradation (By similarity). Interacts with UBR2, as part of a SCF(BTRC) complex; the interaction mediates 'Lys-48'-linked ubiquitination of UBR2 and is regulated by DUSP22 in the T-cell receptor signaling pathway (PubMed:38225265)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23468625"}],"value":"(Microbial infection) Interacts with vaccinia virus A49; this interaction inhibits NF-kappa-B activation"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9660940"}],"value":"(Microbial infection) Interacts with HIV-1 Vpu"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q5JTC6","geneName":"AMER1","intActId":"EBI-6169747"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"P18848","geneName":"ATF4","intActId":"EBI-492498"},"numberOfExperiments":21,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q9Y2T1","geneName":"AXIN2","intActId":"EBI-4400025"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q76N32","geneName":"CEP68","intActId":"EBI-9051024"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q7L5N1","geneName":"COPS6","intActId":"EBI-486838"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"P35222","geneName":"CTNNB1","intActId":"EBI-491549"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q13616","geneName":"CUL1","intActId":"EBI-359390"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q12959","geneName":"DLG1","intActId":"EBI-357481"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"P10070","geneName":"GLI2","intActId":"EBI-10821567"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"P28799","geneName":"GRN","intActId":"EBI-747754"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q13651","geneName":"IL10RA","intActId":"EBI-1031656"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q3KP66","geneName":"INAVA","intActId":"EBI-7545562"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q8WXH2","geneName":"JPH3","intActId":"EBI-1055254"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q02750","geneName":"MAP2K1","intActId":"EBI-492564"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q00987","geneName":"MDM2","intActId":"EBI-389668"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"P49821","geneName":"NDUFV1","intActId":"EBI-748312"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q15843","geneName":"NEDD8","intActId":"EBI-716247"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q16621","geneName":"NFE2","intActId":"EBI-726369"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q16236","geneName":"NFE2L2","intActId":"EBI-2007911"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q5HYW2","geneName":"NHSL2","intActId":"EBI-2859639"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"O00444","geneName":"PLK4","intActId":"EBI-746202"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q99952","geneName":"PTPN18","intActId":"EBI-1384210"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9Y297","intActId":"EBI-307461"},"interactantTwo":{"uniProtKBAccession":"Q99952-1","geneName":"PTPN18","intActId":"EBI-12739708"},"numberOfExperiments":2,"organismDi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LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3ULA2"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3ULA2"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9Y297-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9Y297-2"],"sequenceIds":["VSP_006764"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20736409"}],"value":"Expressed in epididymis (at protein level)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17574027"}],"value":"The N-terminal D domain mediates 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