FBXW7_RAT
ID FBXW7_RAT Reviewed; 713 AA.
AC D3Z902;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=F-box/WD repeat-containing protein 7 {ECO:0000305};
GN Name=Fbxw7 {ECO:0000312|RGD:2321145};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|Proteomes:UP000002494};
RN [1] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000305}
RP INTERACTION WITH PRR7.
RX PubMed=27458189; DOI=10.15252/embj.201593070;
RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S.,
RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.;
RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates
RT NMDA-mediated excitotoxicity.";
RL EMBO J. 35:1923-1934(2016).
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 (By similarity). Recognizes and binds phosphorylated
CC sites/phosphodegrons within target proteins and thereafter brings them
CC to the SCF complex for ubiquitination (By similarity). Identified
CC substrates include cyclin-E (CCNE1 or CCNE2), JUN, MYC, NOTCH1 released
CC notch intracellular domain (NICD), NOTCH2, MCL1, RICTOR and probably
CC PSEN1 (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 (By similarity).
CC Involved in bone homeostasis and negative regulation of osteoclast
CC differentiation (By similarity). Regulates the amplitude of the cyclic
CC expression of hepatic core clock genes and genes involved in lipid and
CC glucose metabolism via ubiquitination and proteasomal degradation of
CC their transcriptional repressor NR1D1; CDK1-dependent phosphorylation
CC of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (By
CC similarity). Also able to promote 'Lys-63'-linked ubiquitination in
CC response to DNA damage (By similarity). The SCF(FBXW7) complex
CC facilitates double-strand break repair following phosphorylation by
CC ATM: phosphorylation promotes localization to sites of double-strand
CC breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4,
CC enhancing DNA non-homologous end joining (By similarity).
CC {ECO:0000250|UniProtKB:Q8VBV4, ECO:0000250|UniProtKB:Q969H0}.
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 (By
CC similarity). Interacts (via F-box domain) with SKP1. Interacts (via F-
CC box domain) with pseudophosphatase STYX; the interaction is direct and
CC prevents FBXW7 interaction with SKP1 (By similarity). Interacts with
CC cyclin-E (CCNE1 or CCNE2) (By similarity). Interacts with PSEN1 (By
CC similarity). Forms a trimeric complex with NOTCH1 and SGK1 (By
CC similarity). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4
CC intracellular domain/NICD (By similarity). Interacts with NOTCH2
CC intracellular 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-211) 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 (PubMed:27458189).
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 (By
CC similarity). Interacts with NR1D1 (By similarity). Interacts with
CC RICTOR; mediates RICTOR ubiquitination and degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q8VBV4, ECO:0000250|UniProtKB:Q969H0,
CC ECO:0000269|PubMed:27458189}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q969H0}. 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 -!- 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-211 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 211 and subsequent interaction with PIN1. Ubiquitination leads to its
CC degradation. {ECO:0000250|UniProtKB:Q969H0}.
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DR EMBL; AABR07012054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07012055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07012056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; D3Z902; -.
DR SMR; D3Z902; -.
DR CORUM; D3Z902; -.
DR STRING; 10116.ENSRNOP00000050193; -.
DR PaxDb; D3Z902; -.
DR PeptideAtlas; D3Z902; -.
DR Ensembl; ENSRNOT00000052051; ENSRNOP00000050193; ENSRNOG00000010889.
DR RGD; 2321145; Fbxw7.
DR eggNOG; KOG0274; Eukaryota.
DR GeneTree; ENSGT00940000154986; -.
DR InParanoid; D3Z902; -.
DR OrthoDB; 927943at2759; -.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:D3Z902; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000010889; Expressed in frontal cortex and 18 other tissues.
DR ExpressionAtlas; D3Z902; baseline and differential.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0050816; F:phosphothreonine residue binding; ISO:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
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:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0097027; F:ubiquitin-protein transferase activator activity; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:2001205; P:negative regulation of osteoclast development; ISO:RGD.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISO:RGD.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; ISO:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:RGD.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; ISO:RGD.
DR GO; GO:0010992; P:ubiquitin recycling; IBA:GO_Central.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
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 Biological rhythms; Chromosome; Coiled coil; DNA damage; DNA repair;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..713
FT /note="F-box/WD repeat-containing protein 7"
FT /id="PRO_0000442030"
FT DOMAIN 284..330
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 384..424
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 426..462
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 465..504
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 506..542
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 545..584
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 586..624
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 628..665
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REGION 1..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 94..136
FT /evidence="ECO:0000255"
FT COMPBIAS 17..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..91
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..136
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
SQ SEQUENCE 713 AA; 80367 MW; 3B208792FE3790B9 CRC64;
MNQELLSVGS KRRRTGGSLR GNASSSQVDE EQMNRVVEED PQQQPRHQEE EHTARNGELV
GADPRPGAQN DSQQGQVEEN NNRFVSVDED SSGNQEEQEE DEEHAGEQEE EEEEEEEEEE
EEEMDQESDD FDQSDDSSRE DEHTHNSNVT NCTSVVDLPI NQLSSPFYTK TTKMKRKLDH
GSEVRSFSLG KKPCKVSDYT STTGLVPCSA TPTTFGDLRA ANGQGQQRRR ITSVQPPTGL
QEWLKMFQSW SGPEKLLALD ELIDSCEPTQ VKHMMQVIEP QFQRDFISLL PKELALYVLS
FLEPKDLLQA AQTCRYWRIL AEDNLLWREK CKEEGIDEPL HIKRRKIIKP GFIHSPWKSA
YIRQHRIDTN WRRGELRSPK VLKGHDDHVI TCLQFCGNRI VSGSDDNTLK VWSAVTGKCL
RTLVGHTGGV WSSQMRDNII ISGSTDRTLK VWNAETGECI HTLYGHTSTV RCMHLHEKRV
VSGSRDATLR VWDIETGQCL HVLMGHVAAV RCVQYDGRRV VSGAYDFMVK VWDPETETCL
HTLQGHTNRV YSLQFDGIHV VSGSLDTSIR VWDVETGNCI HTLTGHQSLT SGMELKDNIL
VSGNADSTVK IWDIKTGQCL QTLQGPSKHQ SAVTCLQFNK NFVITSSDDG TVKLWDLKTG
EFIRNLVTLE SGGSGGVVWR IRASNTKLVC AVGSRNGTEE TKLLVLDFDV DMK
