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MGP005414

UniProt Annotations

Entry Information
Gene NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Protein EntryFBXW7_HUMAN
UniProt IDQ969H0
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Archipelago alpha, FBW7alpha, 110K, common; IsoId=Q969H0-1; Sequence=Displayed; Name=2; Synonyms=Archipelago beta, FBW7beta, 69K; IsoId=Q969H0-2; Sequence=VSP_009483, VSP_009484; Note=Ref.6 (AAH37320) sequence is in conflict in position: 7:G->V. Ref.7 (BAA91986) sequence is in conflict in position: 50:L->I. {ECO:0000305}; Name=3; Synonyms=Archipelago gamma, FBW7gamma, Hippocampal; IsoId=Q969H0-4; Sequence=VSP_009482, VSP_009485;
DomainThe F-box domain mediates interaction with SKP1. {ECO:0000269|PubMed:17434132}.
DomainThe WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:17434132}.
FunctionSubstrate recognition component of an SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination. Identified substrates include cyclin-E, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522}.
InteractionSelf; NbExp=3; IntAct=EBI-359574, EBI-359574; Q16204:CCDC6; NbExp=9; IntAct=EBI-359574, EBI-1045350; P24941:CDK2; NbExp=2; IntAct=EBI-6502391, EBI-375096; P01106:MYC; NbExp=4; IntAct=EBI-359574, EBI-447544; P63208:SKP1; NbExp=5; IntAct=EBI-359574, EBI-307486; Q9UBI4:STOML1; NbExp=3; IntAct=EBI-6502391, EBI-2681162;
Sequence CautionSequence=BAA91986.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityContains 1 F-box domain. {ECO:0000255|PROSITE- ProRule:PRU00080}.
SimilarityContains 7 WD repeats. {ECO:0000255|PROSITE- ProRule:PRU00221}.
Subcellular LocationIsoform 1: Nucleus, nucleoplasm.
Subcellular LocationIsoform 2: Cytoplasm.
Subcellular LocationIsoform 3: Nucleus, nucleolus.
Subcellular LocationNucleus {ECO:0000250}.
SubunitHomodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (PubMed:17434132). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7. Interacts with PSEN1, cyclin E, NOTCH1 intracellular domain/NICD, NOTCH4 intracellular domain/NICD and SKP1. Interacts with MYC (when phosphorylated). Isoform 1 interacts with USP28, leading to counteract ubiquitination of MYC. Isoform 3 interacts (via WD repeats) with SV40 large T antigen (via CPD region). Forms a trimeric complex with NOTCH1 and SGK1. {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:12354302, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:15611062, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:21147854}.
Tissue SpecificityIsoform 1 is widely expressed. Isoform 3 is expressed in brain. {ECO:0000269|PubMed:12354302}.
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