FBXW7_MOUSE
ID FBXW7_MOUSE Reviewed; 710 AA.
AC Q8VBV4; A2RRI5; D3YUA5; Q8CCS5; Q8VHP4;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 25-APR-2018, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=F-box/WD repeat-containing protein 7 {ECO:0000305};
DE AltName: Full=F-box and WD-40 domain-containing protein 7 {ECO:0000312|MGI:MGI:1354695};
DE AltName: Full=F-box protein FBW7 {ECO:0000305};
DE AltName: Full=F-box protein Fbxw6 {ECO:0000303|PubMed:11735228};
DE AltName: Full=F-box-WD40 repeat protein 6 {ECO:0000303|PubMed:11735228};
DE AltName: Full=SEL-10 {ECO:0000303|PubMed:11425854};
GN Name=Fbxw7 {ECO:0000312|MGI:MGI:1354695};
GN Synonyms=Fbw7 {ECO:0000305}, Fbwd6 {ECO:0000312|EMBL:AAL50052.1},
GN Fbxw6 {ECO:0000312|EMBL:AAL40930.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INTERACTION WITH
RP SKP1 AND CUL1.
RC STRAIN=129/Sv;
RX PubMed=11735228; DOI=10.1006/geno.2001.6658;
RA Maruyama S., Hatakeyama S., Nakayama K., Ishida N., Kawakami K.,
RA Nakayama K.;
RT "Characterization of a mouse gene (Fbxw6) that encodes a homologue of
RT Caenorhabditis elegans SEL-10.";
RL Genomics 78:214-222(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ilyin G.P.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 386-710.
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP INTERACTION WITH NOTCH1 NICD.
RX PubMed=11425854; DOI=10.1074/jbc.m101343200;
RA Gupta-Rossi N., Le Bail O., Gonen H., Brou C., Logeat F., Six E.,
RA Ciechanover A., Israel A.;
RT "Functional interaction between SEL-10, an F-box protein, and the nuclear
RT form of activated Notch1 receptor.";
RL J. Biol. Chem. 276:34371-34378(2001).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NOTCH1 NICD.
RX PubMed=11461910; DOI=10.1074/jbc.m103992200;
RA Oeberg C., Li J., Pauley A., Wolf E., Gurney M., Lendahl U.;
RT "The Notch intracellular domain is ubiquitinated and negatively regulated
RT by the mammalian Sel-10 homolog.";
RL J. Biol. Chem. 276:35847-35853(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH NFE2L1.
RX PubMed=21953459; DOI=10.1074/jbc.m111.253807;
RA Biswas M., Phan D., Watanabe M., Chan J.Y.;
RT "The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1
RT transcription factor turnover through proteasome-mediated proteolysis.";
RL J. Biol. Chem. 286:39282-39289(2011).
RN [9]
RP FUNCTION, AND UBIQUITINATION.
RX PubMed=22748924; DOI=10.1016/j.molcel.2012.05.044;
RA Duda D.M., Olszewski J.L., Tron A.E., Hammel M., Lambert L.J.,
RA Waddell M.B., Mittag T., DeCaprio J.A., Schulman B.A.;
RT "Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase
RT through masking of its E2-binding surface.";
RL Mol. Cell 47:371-382(2012).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27238018; DOI=10.1016/j.cell.2016.05.012;
RA Zhao X., Hirota T., Han X., Cho H., Chong L.W., Lamia K., Liu S.,
RA Atkins A.R., Banayo E., Liddle C., Yu R.T., Yates J.R. III, Kay S.A.,
RA Downes M., Evans R.M.;
RT "Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha
RT degradation.";
RL Cell 165:1644-1657(2016).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29149593; DOI=10.1016/j.molcel.2017.10.018;
RA Fukushima H., Shimizu K., Watahiki A., Hoshikawa S., Kosho T., Oba D.,
RA Sakano S., Arakaki M., Yamada A., Nagashima K., Okabe K., Fukumoto S.,
RA Jimi E., Bigas A., Nakayama K.I., Nakayama K., Aoki Y., Wei W., Inuzuka H.;
RT "NOTCH2 Hajdu-Cheney mutations escape SCFFBW7-dependent proteolysis to
RT promote osteoporosis.";
RL Mol. Cell 68:645-658(2017).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins (PubMed:21953459, PubMed:22748924). Recognizes and binds
CC phosphorylated sites/phosphodegrons within target proteins and
CC thereafter brings them to the SCF complex for ubiquitination
CC (PubMed:22748924). Mediates ubiquitination and subsequent degradation
CC of CCNE1 and MYC (PubMed:22748924). Identified substrates include
CC cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch
CC intracellular domain (NICD), NOTCH2, MCL1, RICTOR and probably PSEN1
CC (By similarity). Acts as a negative regulator of JNK signaling by
CC binding to phosphorylated JUN and promoting its ubiquitination and
CC subsequent degradation (By similarity). SCF(FBXW7) complex mediates the
CC ubiquitination and subsequent degradation of NFE2L1 (PubMed:21953459).
CC Involved in bone homeostasis and negative regulation of osteoclast
CC differentiation (PubMed:29149593). Regulates the amplitude of the
CC cyclic expression of hepatic core clock genes and genes involved in
CC lipid and glucose metabolism via ubiquitination and proteasomal
CC degradation of their transcriptional repressor NR1D1; CDK1-dependent
CC phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated
CC ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked
CC ubiquitination in response to DNA damage (By similarity). The
CC SCF(FBXW7) complex facilitates double-strand break repair following
CC phosphorylation by ATM: phosphorylation promotes localization to sites
CC of double-strand breaks and 'Lys-63'-linked ubiquitination of
CC phosphorylated XRCC4, enhancing DNA non-homologous end joining (By
CC similarity). {ECO:0000250|UniProtKB:Q969H0,
CC ECO:0000269|PubMed:16141072, ECO:0000269|PubMed:21953459,
CC ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:27238018,
CC ECO:0000269|PubMed:29149593}.
CC -!- SUBUNIT: Homodimer; homodimerization plays a role in substrate binding
CC and/or ubiquitination and degradation (By similarity). Component of the
CC SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7
CC (PubMed:11735228). Interacts (via F-box domain) with SKP1
CC (PubMed:11735228). Interacts (via F-box domain) with pseudophosphatase
CC STYX; the interaction is direct and prevents FBXW7 interaction with
CC SKP1 (By similarity). Interacts with cyclin-E (CCNE1 or CCNE2) (By
CC similarity). Interacts with PSEN1 (By similarity). Forms a trimeric
CC complex with NOTCH1 and SGK1 (By similarity). Interacts with NOTCH1
CC intracellular domain/NICD and NOTCH4 intracellular domain/NICD
CC (PubMed:11425854, PubMed:11461910). Interacts with NOTCH2 intracellular
CC domain (N2ICD) (By similarity). Interacts with MYC (when
CC phosphorylated) (By similarity). Interacts with USP28, counteracting
CC ubiquitination of MYC (By similarity). Interacts (when phosphorylated
CC at Thr-208) with PIN1, disrupting FBXW7 dimerization and promoting
CC FBXW7 autoubiquitination and degradation (By similarity). Interacts
CC with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7
CC degradation (By similarity). Interacts with MYCN; FBXW7 competes with
CC AURKA for binding to unphosphorylated MYCN but not for binding to
CC phosphorylated MYCN (By similarity). Interacts with JUN (By
CC similarity). Found in a complex with JUN and PRR7 (By similarity).
CC Interacts with JUN and PRR7; the interaction inhibits ubiquitination-
CC mediated JUN degradation, promoting its phosphorylation and
CC transcriptional activity (By similarity). Interacts with NFE2L1
CC (PubMed:21953459). Interacts with NR1D1 (By similarity). Interacts with
CC RICTOR; mediates RICTOR ubiquitination and degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q969H0, ECO:0000269|PubMed:11425854,
CC ECO:0000269|PubMed:11461910, ECO:0000269|PubMed:11735228,
CC ECO:0000269|PubMed:21953459}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:11461910}. Chromosome
CC {ECO:0000250|UniProtKB:Q969H0}. Note=Localizes to site of double-strand
CC breaks following phosphorylation by ATM.
CC {ECO:0000250|UniProtKB:Q969H0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VBV4-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VBV4-1; Sequence=VSP_059530;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in brain,
CC heart and testis. {ECO:0000269|PubMed:11735228}.
CC -!- DOMAIN: The WD repeats mediate interaction with substrates of the SCF
CC (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.
CC {ECO:0000250|UniProtKB:Q969H0}.
CC -!- DOMAIN: The F-box domain mediates interaction with SKP1.
CC {ECO:0000250|UniProtKB:Q969H0}.
CC -!- PTM: Phosphorylation at Thr-208 promotes interaction with PIN1, leading
CC to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination
CC and degradation. Phosphorylated by ATM at Ser-26 in response to DNA
CC damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked
CC ubiquitination of phosphorylated XRCC4. {ECO:0000250|UniProtKB:Q969H0}.
CC -!- PTM: Ubiquitinated: autoubiquitinates following phosphorylation at Thr-
CC 208 and subsequent interaction with PIN1 (By similarity).
CC Ubiquitination leads to its proteasomal degradation (PubMed:22748924).
CC {ECO:0000250|UniProtKB:Q969H0, ECO:0000269|PubMed:22748924}.
CC -!- DISRUPTION PHENOTYPE: Whole body FBW7 knockout is embryonic lethal.
CC Conditional knockout mice in which FBW7 expression is specifically
CC abolished in osteoclasts display severe bone resorption, bone fragility
CC and low bone mass (PubMed:29149593). Conditional knockout in liver
CC reduces the amplitude of the diurnal expression of many core clock
CC genes and the altered expression of a large number of genes controlling
CC liver metabolic pathways (PubMed:27238018).
CC {ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:29149593}.
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DR EMBL; AF391202; AAL40930.1; -; Genomic_DNA.
DR EMBL; AF391193; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391194; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391195; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391196; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391197; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391198; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391199; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391200; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391201; AAL40930.1; JOINED; Genomic_DNA.
DR EMBL; AF391192; AAL40928.1; -; mRNA.
DR EMBL; AF427101; AAL50052.1; -; mRNA.
DR EMBL; AC124496; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC158583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC131648; AAI31649.1; -; mRNA.
DR EMBL; AK032174; BAC27743.1; -; mRNA.
DR CCDS; CCDS17440.1; -. [Q8VBV4-1]
DR CCDS; CCDS50940.1; -. [Q8VBV4-2]
DR RefSeq; NP_001171244.1; NM_001177773.1. [Q8VBV4-2]
DR RefSeq; NP_001171245.1; NM_001177774.1. [Q8VBV4-2]
DR RefSeq; NP_536353.2; NM_080428.3. [Q8VBV4-1]
DR RefSeq; XP_006501719.1; XM_006501656.3. [Q8VBV4-2]
DR RefSeq; XP_006501720.1; XM_006501657.3. [Q8VBV4-2]
DR AlphaFoldDB; Q8VBV4; -.
DR SMR; Q8VBV4; -.
DR BioGRID; 206088; 56.
DR DIP; DIP-61083N; -.
DR IntAct; Q8VBV4; 3.
DR MINT; Q8VBV4; -.
DR STRING; 10090.ENSMUSP00000103306; -.
DR iPTMnet; Q8VBV4; -.
DR PhosphoSitePlus; Q8VBV4; -.
DR jPOST; Q8VBV4; -.
DR PaxDb; Q8VBV4; -.
DR PRIDE; Q8VBV4; -.
DR ProteomicsDB; 271558; -. [Q8VBV4-2]
DR ProteomicsDB; 332538; -.
DR Antibodypedia; 27779; 681 antibodies from 36 providers.
DR DNASU; 50754; -.
DR Ensembl; ENSMUST00000029727; ENSMUSP00000029727; ENSMUSG00000028086. [Q8VBV4-1]
DR Ensembl; ENSMUST00000107678; ENSMUSP00000103305; ENSMUSG00000028086. [Q8VBV4-2]
DR Ensembl; ENSMUST00000107679; ENSMUSP00000103306; ENSMUSG00000028086. [Q8VBV4-2]
DR GeneID; 50754; -.
DR KEGG; mmu:50754; -.
DR UCSC; uc008pqk.2; mouse.
DR UCSC; uc008pql.2; mouse. [Q8VBV4-2]
DR CTD; 55294; -.
DR MGI; MGI:1354695; Fbxw7.
DR VEuPathDB; HostDB:ENSMUSG00000028086; -.
DR eggNOG; KOG0274; Eukaryota.
DR GeneTree; ENSGT00940000154986; -.
DR InParanoid; Q8VBV4; -.
DR OrthoDB; 927943at2759; -.
DR PhylomeDB; Q8VBV4; -.
DR TreeFam; TF101074; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 50754; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Fbxw7; mouse.
DR PRO; PR:Q8VBV4; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8VBV4; protein.
DR Bgee; ENSMUSG00000028086; Expressed in retrosplenial region and 251 other tissues.
DR ExpressionAtlas; Q8VBV4; baseline and differential.
DR Genevisible; Q8VBV4; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050816; F:phosphothreonine residue binding; ISS:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; TAS:Reactome.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0097027; F:ubiquitin-protein transferase activator activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:2001205; P:negative regulation of osteoclast development; IMP:UniProtKB.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:ParkinsonsUK-UCL.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:ParkinsonsUK-UCL.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0031648; P:protein destabilization; IDA:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:MGI.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IMP:CACAO.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010992; P:ubiquitin recycling; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; IMP:MGI.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF00400; WD40; 7.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00320; WD40; 8.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 5.
DR PROSITE; PS50082; WD_REPEATS_2; 7.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; Chromosome; DNA damage;
KW DNA repair; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..710
FT /note="F-box/WD repeat-containing protein 7"
FT /id="PRO_0000050995"
FT DOMAIN 281..327
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 381..421
FT /note="WD 1"
FT REPEAT 423..459
FT /note="WD 2"
FT REPEAT 462..501
FT /note="WD 3"
FT REPEAT 503..539
FT /note="WD 4"
FT REPEAT 542..581
FT /note="WD 5"
FT REPEAT 583..621
FT /note="WD 6"
FT REPEAT 625..662
FT /note="WD 7"
FT REGION 1..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..133
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..158
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT MOD_RES 230
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT VAR_SEQ 1..169
FT /note="MNQELLSVGSKRRRTGGSLRGNASSSQVDEGQMNRVVEEDPQQQARHQEEEH
FT TARNGELVGANPRPGDQNDTQQGQVEENNNRFISVDEDSSGNQEEQEEDEEHAGEQEEE
FT EEEEEEEEEMDQESDDFDPSDDSSREDEHTHNSNVTNCSSVSDLPAHQLSSPFYTKTT
FT -> MRVCVPSSVLVLSCVCWCWGVLLPVPLPNLPFLACLSMSTLESVTYLPEKGLYCQR
FT LPSSRTHGGTESLKGKNTENMGFYGTLKMIFY (in isoform 2)"
FT /id="VSP_059530"
FT CONFLICT 73
FT /note="Q -> R (in Ref. 2; AAL50052)"
FT /evidence="ECO:0000305"
FT CONFLICT 621
FT /note="Q -> E (in Ref. 2; AAL50052)"
FT /evidence="ECO:0000305"
FT CONFLICT 700
FT /note="L -> F (in Ref. 2; AAL50052)"
FT /evidence="ECO:0000305"
FT CONFLICT 705
FT /note="F -> V (in Ref. 2; AAL50052)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 710 AA; 79848 MW; 9D56F7E81E6E390B CRC64;
MNQELLSVGS KRRRTGGSLR GNASSSQVDE GQMNRVVEED PQQQARHQEE EHTARNGELV
GANPRPGDQN DTQQGQVEEN NNRFISVDED SSGNQEEQEE DEEHAGEQEE EEEEEEEEEE
MDQESDDFDP SDDSSREDEH THNSNVTNCS SVSDLPAHQL SSPFYTKTTK MKRKLDHGSE
VRSFSLGKKP CKVSDYTSTT GLVPCSATPT TFGDLRAANG QGQQRRRITS VQPPTGLQEW
LKMFQSWSGP EKLLALDELI DSCEPTQVKH MMQVIEPQFQ RDFISLLPKE LALYVLSFLE
PKDLLQAAQT CRYWRILAED NLLWREKCKE EGIDEPLHIK RRKIIKPGFI HSPWKSAYIR
QHRIDTNWRR GELKSPKVLK GHDDHVITCL QFCGNRIVSG SDDNTLKVWS AVTGKCLRTL
VGHTGGVWSS QMRDNIIISG STDRTLKVWN AETGECIHTL YGHTSTVRCM HLHEKRVVSG
SRDATLRVWD IETGQCLHVL MGHVAAVRCV QYDGRRVVSG AYDFMVKVWD PETETCLHTL
QGHTNRVYSL QFDGIHVVSG SLDTSIRVWD VETGNCIHTL TGHQSLTSGM ELKDNILVSG
NADSTVKIWD IKTGQCLQTL QGPSKHQSAV TCLQFNKNFV ITSSDDGTVK LWDLKTGEFI
RNLVTLESGG SGGVVWRIRA SNTKLVCAVG SRNGTEETKL LVLDFDVDMK
