{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q969H0","secondaryAccessions":["B7ZLP9","Q68DR0","Q96A16","Q96LE0","Q96RI2","Q9NUX6"],"uniProtkbId":"FBXW7_HUMAN","entryAudit":{"firstPublicDate":"2004-03-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2001-12-01","entryVersion":214,"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:0000305"}],"value":"F-box/WD repeat-containing protein 7"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11565033"}],"value":"Archipelago homolog"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11565033"}],"value":"hAgo"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"F-box and WD-40 domain-containing protein 7"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"10531037"}],"value":"F-box protein FBX30"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12354302"}],"value":"SEL-10"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11565034"}],"value":"hCdc4"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:16712"}],"value":"FBXW7"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAK57547.1"}],"value":"FBW7"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAK60269.1"}],"value":"FBX30"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAL07271.1"}],"value":"SEL10"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11565034"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11585921"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14739463"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15103331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17434132"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17558397"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17873522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22608923"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22748924"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25775507"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25897075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26774286"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26976582"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27238018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28007894"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28727686"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29149593"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34102342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34741373"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35395208"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12354302"}],"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:17434132, PubMed:22748924, PubMed:26976582, PubMed:28727686, PubMed:34741373, PubMed:35395208). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:17434132, PubMed:22748924, PubMed:26774286, PubMed:26976582, PubMed:28727686, PubMed:34741373). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:11585921, PubMed:12354302, PubMed:14739463, PubMed:15103331, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:25775507, PubMed:25897075, PubMed:26976582, PubMed:28007894, PubMed:28727686, PubMed:29149593, PubMed:34102342). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15103331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25897075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34741373"}],"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8VBV4"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11565034"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11585921"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12354302"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14739463"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15103331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15611062"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17434132"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17558397"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17873522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21147854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22608923"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23082202"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24000165"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24344117"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25897075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26774286"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27238018"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27458189"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27837025"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28007894"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29149593"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34102342"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34741373"}],"value":"Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (PubMed:17434132, PubMed:22608923, PubMed:28007894). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11565034, PubMed:15103331, PubMed:22748924, PubMed:26774286, PubMed:26976582, PubMed:28007894, PubMed:28727686, PubMed:34741373). Interacts (via F-box domain) with SKP1 (PubMed:11585921, PubMed:17434132, PubMed:26976582, PubMed:28007894, PubMed:28727686). Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (PubMed:28007894). Interacts with cyclin-E (CCNE1 or CCNE2) (PubMed:11565034, PubMed:17434132). Interacts with PSEN1 (PubMed:12354302). Forms a trimeric complex with NOTCH1 and SGK1 (PubMed:21147854). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (PubMed:11585921). Interacts with NOTCH2 intracellular domain (N2ICD) (PubMed:29149593). Interacts with MYC (when phosphorylated) (PubMed:17873522, PubMed:25775507, PubMed:28007894). Interacts with USP28, counteracting ubiquitination of MYC (PubMed:17873522). Interacts with JUN (PubMed:14739463, PubMed:22608923). Found in a complex with JUN and PRR7 (PubMed:27458189). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation, promoting its phosphorylation and transcriptional activity (PubMed:27458189). Interacts (when phosphorylated at Thr-205) with PIN1, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Interacts with UBE2QL1 (PubMed:24000165). Interacts with FAM83D; promotes FBXW7 degradation (PubMed:24344117). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025). Interacts with STOML1 (PubMed:23082202). Interacts with NFE2L1 (By similarity). Interacts with USP36, counteracting ubiquitination of MYC (PubMed:25775507). Interacts with NR1D1 (PubMed:27238018). Interacts with RICTOR; mediates RICTOR ubiquitination and degradation (PubMed:25897075). Interacts with USP38, counteracting ubiquitination of MYC (PubMed:34102342)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15611062"}],"value":"(Microbial infection) Interacts (via WD repeats) with SV40 large T antigen (via CPD region)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P31749","geneName":"AKT1","intActId":"EBI-296087"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q16204","geneName":"CCDC6","intActId":"EBI-1045350"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P24385","geneName":"CCND1","intActId":"EBI-375001"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P11802","geneName":"CDK4","intActId":"EBI-295644"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P46527","geneName":"CDKN1B","intActId":"EBI-519280"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q13616","geneName":"CUL1","intActId":"EBI-359390"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q00597","geneName":"FANCC","intActId":"EBI-81625"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q969H0","geneName":"FBXW7","intActId":"EBI-359574"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P01112","geneName":"HRAS","intActId":"EBI-350145"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P08238","geneName":"HSP90AB1","intActId":"EBI-352572"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P52333","geneName":"JAK3","intActId":"EBI-518246"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q16539","geneName":"MAPK14","intActId":"EBI-73946"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P42345","geneName":"MTOR","intActId":"EBI-359260"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P01106","geneName":"MYC","intActId":"EBI-447544"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P04198","geneName":"MYCN","intActId":"EBI-878369"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P46531","geneName":"NOTCH1","intActId":"EBI-636374"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P63208","geneName":"SKP1","intActId":"EBI-307486"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"P63208-1","geneName":"SKP1","intActId":"EBI-307497"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q15797","geneName":"SMAD1","intActId":"EBI-1567153"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q8WUJ0","geneName":"STYX","intActId":"EBI-20979851"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q9NR00","geneName":"TCIM","intActId":"EBI-2843495"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q9Z0Z7","geneName":"Klf5","intActId":"EBI-647919"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q969H0","intActId":"EBI-359574"},"interactantTwo":{"uniProtKBAccession":"Q91LX9","intActId":"EBI-15662601"},"numberOfExperiments":5,"organismDiffer":true},{"interactantO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3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17434132"}],"value":"The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17434132"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28007894"}],"value":"The F-box domain mediates interaction with SKP1"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22608923"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26774286"}],"value":"Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4 (PubMed:26774286)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22608923"}],"value":"Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation (PubMed:22608923)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Developmental delay, hypotonia, and impaired language","diseaseAccession":"DI-06489","acronym":"DEDHIL","description":"An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, borderline to severe intellectual disability, language difficulties, hypotonia, and gastrointestinal problems. Brain imaging shows variable structural abnormalities affecting the cerebellum, corpus collosum, and white matter.","diseaseCrossReference":{"database":"MIM","id":"620012"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35395208"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAA91986.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":707,"modifier":"EXACT"}},"description":"F-box/WD repeat-containing protein 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