FBXW7_BOVIN
ID FBXW7_BOVIN Reviewed; 706 AA.
AC F1MNN4; A0A3Q1N420; Q0VCX6;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 3.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=F-box/WD repeat-containing protein 7 {ECO:0000250|UniProtKB:Q969H0};
DE AltName: Full=F-box and WD-40 domain-containing protein 7;
GN Name=FBXW7 {ECO:0000250|UniProtKB:Q969H0};
GN Synonyms=FBW7 {ECO:0000250|UniProtKB:Q969H0};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Hereford; TISSUE=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH T.ANNULATA PIN1, AND UBIQUITINATION.
RX PubMed=25624101; DOI=10.1038/nature14044;
RA Marsolier J., Perichon M., DeBarry J.D., Villoutreix B.O., Chluba J.,
RA Lopez T., Garrido C., Zhou X.Z., Lu K.P., Fritsch L., Ait-Si-Ali S.,
RA Mhadhbi M., Medjkane S., Weitzman J.B.;
RT "Theileria parasites secrete a prolyl isomerase to maintain host leukocyte
RT transformation.";
RL Nature 520:378-382(2015).
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. Recognizes and binds phosphorylated sites/phosphodegrons
CC within target proteins and thereafter brings them to the SCF complex
CC for ubiquitination (By similarity). 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 Acts as a negative regulator of JNK signaling by binding to
CC phosphorylated JUN and promoting its ubiquitination and subsequent
CC 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). 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:Q8VBV4,
CC ECO:0000250|UniProtKB:Q969H0}.
CC -!- SUBUNIT: Homodimer; homodimerization plays a role in substrate binding
CC and/or ubiquitination and degradation. Component of the SCF(FBXW7)
CC complex consisting of CUL1, RBX1, SKP1 and FBXW7. Interacts (via F-box
CC domain) with SKP1. Interacts (via F-box domain) with pseudophosphatase
CC STYX; the interaction is direct and prevents FBXW7 interaction with
CC SKP1. Interacts with cyclin-E (CCNE1 or CCNE2). Interacts with PSEN1.
CC Forms a trimeric complex with NOTCH1 and SGK1. Interacts with NOTCH1
CC intracellular domain/NICD and NOTCH4 intracellular domain/NICD.
CC Interacts with NOTCH2 intracellular domain (N2ICD). Interacts with MYC
CC (when phosphorylated). Interacts with USP28, counteracting
CC ubiquitination of MYC. Interacts with JUN. Found in a complex with JUN
CC and PRR7. Interacts with JUN and PRR7; the interaction inhibits
CC ubiquitination-mediated JUN degradation, promoting its phosphorylation
CC and transcriptional activity. Interacts (when phosphorylated at Thr-
CC 204) with PIN1, disrupting FBXW7 dimerization and promoting FBXW7
CC autoubiquitination and degradation. Interacts with UBE2QL1. Interacts
CC with FAM83D; promotes FBXW7 degradation. Interacts with MYCN; FBXW7
CC competes with AURKA for binding to unphosphorylated MYCN but not for
CC binding to phosphorylated MYCN. Interacts with STOML1. Interacts with
CC NFE2L1. Interacts with USP36, counteracting ubiquitination of MYC.
CC Interacts with RICTOR; mediates RICTOR ubiquitination and degradation.
CC {ECO:0000250|UniProtKB:Q8VBV4, ECO:0000250|UniProtKB:Q969H0}.
CC -!- SUBUNIT: (Microbial infection) In case of infection, interacts with
CC T.annulata PIN1 (TaPIN1); leading to FBXW7 autoubiquitination and
CC subsequent degradation: FBXW7 degradation promotes stabilization of
CC JUN, which promotes cell transformation (PubMed:25624101).
CC {ECO:0000269|PubMed:25624101}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=F1MNN4-2; Sequence=Displayed;
CC Name=1;
CC IsoId=F1MNN4-1; Sequence=VSP_060882;
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-204 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 204 and subsequent interaction with PIN1 (PubMed:25624101).
CC Ubiquitination leads to its degradation (PubMed:25624101).
CC {ECO:0000250|UniProtKB:Q969H0, ECO:0000269|PubMed:25624101}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DAAA02044177; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC119946; AAI19947.1; -; mRNA.
DR RefSeq; NP_001069717.1; NM_001076249.1. [F1MNN4-1]
DR RefSeq; XP_005217523.1; XM_005217466.3.
DR RefSeq; XP_005217524.1; XM_005217467.3.
DR AlphaFoldDB; F1MNN4; -.
DR SMR; F1MNN4; -.
DR DIP; DIP-61528N; -.
DR IntAct; F1MNN4; 3.
DR STRING; 9913.ENSBTAP00000010457; -.
DR PaxDb; F1MNN4; -.
DR PRIDE; F1MNN4; -.
DR Ensembl; ENSBTAT00000086850; ENSBTAP00000064414; ENSBTAG00000007953. [F1MNN4-2]
DR GeneID; 540932; -.
DR KEGG; bta:540932; -.
DR CTD; 55294; -.
DR VEuPathDB; HostDB:ENSBTAG00000007953; -.
DR eggNOG; KOG0274; Eukaryota.
DR GeneTree; ENSGT00940000154986; -.
DR HOGENOM; CLU_000288_103_7_1; -.
DR InParanoid; F1MNN4; -.
DR OrthoDB; 927943at2759; -.
DR TreeFam; TF101074; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000007953; Expressed in occipital lobe and 104 other tissues.
DR ExpressionAtlas; F1MNN4; baseline.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030126; C:COPI vesicle coat; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0050816; F:phosphothreonine residue binding; ISS:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0097027; F:ubiquitin-protein transferase activator activity; IEA:Ensembl.
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:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:2001205; P:negative regulation of osteoclast development; IEA:Ensembl.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IEA:Ensembl.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; IEA:Ensembl.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; IEA:Ensembl.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0042752; P:regulation of circadian rhythm; IEA:Ensembl.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0007062; P:sister chromatid cohesion; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
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; Chromosome; DNA damage; DNA repair; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..706
FT /note="F-box/WD repeat-containing protein 7"
FT /id="PRO_0000432705"
FT DOMAIN 277..323
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 377..417
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 419..455
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 458..497
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 499..535
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 538..577
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 579..617
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 621..658
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REGION 1..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..57
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 91..129
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 141..157
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 204
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q969H0"
FT VAR_SEQ 1..165
FT /note="MNQELLSVGSKRRRTGGSLRGNPSSSQADEEQMNRVLEEEQQQPRHQEEEHA
FT ARNGEVVGAEPRPGDQNDPQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEED
FT EEEEEMDQESDDFDQSDDSSREDEHTHRNSVTNSNSIVDLPIHQRSSPFYTKTT -> M
FT CVPRSGLILSCICLYCGVLLPVLLPNLPFLTCLSMSTLESVTYLPEKGLYCQRLPNSRT
FT HGGTESLKGKNPENMGFYGTLKMIFY (in isoform 1)"
FT /id="VSP_060882"
FT CONFLICT F1MNN4-1:99
FT /note="R -> N (in Ref. 2; AAI19947)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 706 AA; 79663 MW; 4705609943F62B6C CRC64;
MNQELLSVGS KRRRTGGSLR GNPSSSQADE EQMNRVLEEE QQQPRHQEEE HAARNGEVVG
AEPRPGDQND PQQGQLEENN NRFISVDEDS SGNQEEQEED EEHAGEQDEE DEEEEEMDQE
SDDFDQSDDS SREDEHTHRN SVTNSNSIVD LPIHQRSSPF YTKTTKMKRK LDHGSEVRSF
SLGKKPCKVS EYTSTTGLVP CSATPTTFGD LRAANGQGQQ RRRITSVQPP TGLQEWLKMF
QSWSGPEKLL ALDELIDSCE PTQVKHMMQV IEPQFQRDFI SLLPKELALY VLSFLEPKDL
LQAAQTCRYW RILAEDNLLW REKCKEEGID EPLHIKRRKV IKPGFIHSPW KSAYIRQHRI
DTNWRRGELK SPKVLKGHDD HVITCLQFCG NRIVSGSDDN TLKVWSAVTG KCLRTLVGHT
GGVWSSQMRD NIIISGSTDR TLKVWNAETG ECIHTLYGHT STVRCMHLHE KRVVSGSRDA
TLRVWDIETG QCLHVLMGHV AAVRCVQYDG RRVVSGAYDF MVKVWDPETE TCLHTLQGHT
NRVYSLQFDG IHVVSGSLDT SIRVWDVETG NCIHTLTGHQ SLTSGMELKD NILVSGNADS
TVKIWDIKTG QCLQTLQGPN KHQSAVTCLQ FNKNFVITSS DDGTVKLWDL KTGEFIRNLV
TLESGGSGGV VWRIRASNTK LVCAVGSRNG TEETKLLVLD FDVDMK
