FBX4_MOUSE
ID FBX4_MOUSE Reviewed; 385 AA.
AC Q8CHQ0; E9QPM9; Q99JG8;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=F-box only protein 4;
GN Name=Fbxo4; Synonyms=Fbx4;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 245-385.
RC TISSUE=Osteoblast;
RA Kopecky B.S., Varga F., Klaushofer K.;
RT "Osteoblasts express the mouse F-box protein mFbx4.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, IDENTIFICATION IN A SCF UBIQUITIN-PROTEIN LIGASE COMPLEX,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17081987; DOI=10.1016/j.molcel.2006.09.007;
RA Lin D.I., Barbash O., Kumar K.G., Weber J.D., Harper J.W.,
RA Klein-Szanto A.J., Rustgi A., Fuchs S.Y., Diehl J.A.;
RT "Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-
RT alphaB crystallin) complex.";
RL Mol. Cell 24:355-366(2006).
RN [5]
RP FUNCTION, AND PHOSPHORYLATION AT SER-11.
RX PubMed=18598945; DOI=10.1016/j.ccr.2008.05.017;
RA Barbash O., Zamfirova P., Lin D.I., Chen X., Yang K., Nakagawa H., Lu F.,
RA Rustgi A.K., Diehl J.A.;
RT "Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and
RT contribute to cyclin D1 overexpression in human cancer.";
RL Cancer Cell 14:68-78(2008).
RN [6]
RP INTERACTION WITH TERF1.
RX PubMed=19487455; DOI=10.1083/jcb.200812121;
RA Zhu Q., Meng L., Hsu J.K., Lin T., Teishima J., Tsai R.Y.;
RT "GNL3L stabilizes the TRF1 complex and promotes mitotic transition.";
RL J. Cell Biol. 185:827-839(2009).
RN [7]
RP FUNCTION.
RX PubMed=19767775; DOI=10.1038/onc.2009.287;
RA Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.;
RT "Lysine 269 is essential for cyclin D1 ubiquitylation by the
RT SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent
RT degradation.";
RL Oncogene 28:4317-4325(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex that mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. Promotes ubiquitination of CCND1 and its subsequent
CC proteasomal degradation. Recognizes TERF1 and promotes its
CC ubiquitination together with UBE2D1 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:17081987, ECO:0000269|PubMed:18598945,
CC ECO:0000269|PubMed:19767775}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Directly interacts with SKP1 and CUL1. Part of the
CC SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO4)
CC formed of CUL1, SKP1, RBX1 and FBXO4. Interacts with TERF1; this
CC interaction is prevented in the presence of GNL3L. Identified in a
CC complex with CRYAB and CCND1 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q8CHQ0; P62259: Ywhae; NbExp=2; IntAct=EBI-3895153, EBI-356480;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17081987}.
CC -!- PTM: Phosphorylation at Ser-11 varies during the cell cycle. It is low
CC in resting cells and high in the S phase and the G2/M phase of the cell
CC cycle. Phosphorylation is decreased during late G1 phase.
CC Phosphorylation at Ser-11 is important for homodimerization and for
CC optimal ubiquitin ligase activity towards CCND1.
CC {ECO:0000269|PubMed:18598945}.
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DR EMBL; AC137902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040086; AAH40086.1; -; mRNA.
DR EMBL; AJ300659; CAC36404.1; -; mRNA.
DR CCDS; CCDS27359.1; -.
DR RefSeq; NP_598860.2; NM_134099.2.
DR AlphaFoldDB; Q8CHQ0; -.
DR SMR; Q8CHQ0; -.
DR BioGRID; 222983; 9.
DR IntAct; Q8CHQ0; 2.
DR STRING; 10090.ENSMUSP00000022791; -.
DR iPTMnet; Q8CHQ0; -.
DR PhosphoSitePlus; Q8CHQ0; -.
DR EPD; Q8CHQ0; -.
DR jPOST; Q8CHQ0; -.
DR MaxQB; Q8CHQ0; -.
DR PaxDb; Q8CHQ0; -.
DR PeptideAtlas; Q8CHQ0; -.
DR PRIDE; Q8CHQ0; -.
DR ProteomicsDB; 271678; -.
DR Antibodypedia; 23214; 289 antibodies from 30 providers.
DR DNASU; 106052; -.
DR Ensembl; ENSMUST00000022791; ENSMUSP00000022791; ENSMUSG00000022184.
DR GeneID; 106052; -.
DR KEGG; mmu:106052; -.
DR UCSC; uc007vcf.2; mouse.
DR CTD; 26272; -.
DR MGI; MGI:2146220; Fbxo4.
DR VEuPathDB; HostDB:ENSMUSG00000022184; -.
DR eggNOG; ENOG502QUXD; Eukaryota.
DR GeneTree; ENSGT00390000014416; -.
DR HOGENOM; CLU_064324_0_0_1; -.
DR InParanoid; Q8CHQ0; -.
DR OMA; RQIHGIG; -.
DR OrthoDB; 680454at2759; -.
DR PhylomeDB; Q8CHQ0; -.
DR TreeFam; TF331105; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 106052; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Fbxo4; mouse.
DR PRO; PR:Q8CHQ0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8CHQ0; protein.
DR Bgee; ENSMUSG00000022184; Expressed in saccule of membranous labyrinth and 207 other tissues.
DR Genevisible; Q8CHQ0; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0007568; P:aging; IMP:MGI.
DR GO; GO:0019725; P:cellular homeostasis; IMP:MGI.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:MGI.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; IMP:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:MGI.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; IMP:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:MGI.
DR GO; GO:0031648; P:protein destabilization; IMP:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR039588; FBXO4.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR16008; PTHR16008; 1.
DR Pfam; PF12937; F-box-like; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Phosphoprotein; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..385
FT /note="F-box only protein 4"
FT /id="PRO_0000119880"
FT DOMAIN 54..100
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18598945"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT5"
FT CONFLICT 91
FT /note="I -> V (in Ref. 2; AAH40086)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="H -> R (in Ref. 2; AAH40086)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 385 AA; 43777 MW; 36D78194EAF9EE95 CRC64;
MAGSEPRGAG SPPPASDWGR LEAAILSGWR TFWYSVAKER ATPTASRKEA AEETSALTRL
PVDVQLYILS FLSPHDLCQL GSTDHYWNKT IRDPILWRYF LLRDLPSWSS VDWKSLPDLE
ILKKPISEVT DSTCLDYMEV YKMCCPYTRR ALKASRPMYG VVTSFLHSLI IQNEPRFAMF
GPGLEELNTS LVLSLMSSED LCPTAGLPHR QIDGIGSGVN FQLNNQQKFN ILILYSTTRK
ERDRAREEHT STVNKMFSLQ SEGDEQQGSR YSVIPQIQKV CEVVDGFIYV ANAEAHRRHE
WQDEFSRIMA MTDPAFGSSG RPMLVLSCIS QADVKRMPCF YLAHELHLSL LNHPWMVQDT
EAETLTGFLN GIEWILEEVE SKRAK
