FBXW5_MOUSE
ID FBXW5_MOUSE Reviewed; 573 AA.
AC Q9QXW2; A2AJ36; A2AJ37; E9QMP0; Q3U368;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=F-box/WD repeat-containing protein 5;
DE AltName: Full=F-box and WD-40 domain-containing protein 5;
GN Name=Fbxw5; Synonyms=Fbw5;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION
RP WITH SKP1.
RX PubMed=10531037; DOI=10.1016/s0960-9822(00)80021-4;
RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.;
RT "A family of mammalian F-box proteins.";
RL Curr. Biol. 9:1180-1182(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Testis;
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 [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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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).
RN [7]
RP FUNCTION, AND INTERACTION WITH EPS8.
RX PubMed=23314863; DOI=10.1038/ncb2661;
RA Werner A., Disanza A., Reifenberger N., Habeck G., Becker J., Calabrese M.,
RA Urlaub H., Lorenz H., Schulman B., Scita G., Melchior F.;
RT "SCF(Fbxw5) mediates transient degradation of actin remodeller Eps8 to
RT allow proper mitotic progression.";
RL Nat. Cell Biol. 15:179-188(2013).
RN [8]
RP INTERACTION WITH TNFAIP8L1.
RX PubMed=24444419; DOI=10.1111/jnc.12643;
RA Ha J.Y., Kim J.S., Kang Y.H., Bok E., Kim Y.S., Son J.H.;
RT "Tnfaip8 l1/Oxi-beta binds to FBXW5, increasing autophagy through
RT activation of TSC2 in a Parkinson's disease model.";
RL J. Neurochem. 129:527-538(2014).
CC -!- FUNCTION: Substrate recognition component of both SCF (SKP1-CUL1-F-box
CC protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase
CC complexes. Substrate-specific adapter of the DCX(FBXW5) E3 ubiquitin-
CC protein ligase complex which mediates the polyubiquitination and
CC subsequent degradation of TSC2. May also act as a negative regulator of
CC MAP3K7/TAK1 signaling in the interleukin-1B (IL1B) signaling pathway.
CC Substrate recognition component of the SCF(FBXW5) E3 ubiquitin-protein
CC ligase complex which mediates the ubiquitination and subsequent
CC proteasomal degradation of SASS6 during S phase, leading to prevent
CC centriole reduplication (By similarity). The SCF(FBXW5) complex also
CC mediates ubiquitination and degradation of actin-regulator EPS8 during
CC G2 phase, leading to the transient degradation of EPS8 and subsequent
CC cell shape changes required to allow mitotic progression. {ECO:0000250,
CC ECO:0000269|PubMed:23314863}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXW5) composed of CUL1, SKP1, RBX1 and FBXW5. Component of
CC the DCX(FBXW5) E3 ubiquitin ligase complex, at least composed of (CUL4A
CC or CUL4B), DDB1, FBXW5 and RBX1. Interacts with CDC20, TSC1, TSC2 and
CC SASS6 (By similarity). Interacts with EPS8. Interacts with TNFAIP8L1;
CC TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by
CC preventing its ubiquitination. {ECO:0000250,
CC ECO:0000269|PubMed:10531037, ECO:0000269|PubMed:23314863,
CC ECO:0000269|PubMed:24444419}.
CC -!- INTERACTION:
CC Q9QXW2; Q9WTX5: Skp1; NbExp=2; IntAct=EBI-16031930, EBI-1202363;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q969U6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QXW2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QXW2-2; Sequence=VSP_042293, VSP_042294;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult and embryonal tissues.
CC {ECO:0000269|PubMed:10531037}.
CC -!- DOMAIN: The F-box domain mediates interaction with components of SCF
CC (SKP1-CUL1-F-box protein) complexes, while WD repeats mediate
CC interaction with components of DCX (DDB1-CUL4-X-box) complexes.
CC {ECO:0000250}.
CC -!- DOMAIN: The D-box (destruction box) mediate the interaction with APC
CC proteins, and acts as a recognition signal for degradation via the
CC ubiquitin-proteasome pathway. {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-151 by PLK4 during the G1/S transition,
CC leading to inhibit its ability to ubiquitinate SASS6. {ECO:0000250}.
CC -!- PTM: Ubiquitinated and degraded by the APC/C complex during mitosis and
CC G1 phase. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the FBXW5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM25630.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; AF176520; AAF09130.1; -; mRNA.
DR EMBL; AK019715; BAB31841.1; -; mRNA.
DR EMBL; AK154911; BAE32921.1; -; mRNA.
DR EMBL; AL732557; CAM25629.1; -; Genomic_DNA.
DR EMBL; AL732557; CAM25630.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH466542; EDL08255.1; -; Genomic_DNA.
DR EMBL; BC010776; AAH10776.1; -; mRNA.
DR CCDS; CCDS15778.1; -. [Q9QXW2-1]
DR RefSeq; NP_038936.1; NM_013908.4. [Q9QXW2-1]
DR AlphaFoldDB; Q9QXW2; -.
DR BioGRID; 205976; 4.
DR DIP; DIP-60700N; -.
DR IntAct; Q9QXW2; 1.
DR STRING; 10090.ENSMUSP00000015239; -.
DR iPTMnet; Q9QXW2; -.
DR PhosphoSitePlus; Q9QXW2; -.
DR EPD; Q9QXW2; -.
DR MaxQB; Q9QXW2; -.
DR PaxDb; Q9QXW2; -.
DR PRIDE; Q9QXW2; -.
DR ProteomicsDB; 267720; -. [Q9QXW2-1]
DR ProteomicsDB; 267721; -. [Q9QXW2-2]
DR Antibodypedia; 32276; 163 antibodies from 23 providers.
DR DNASU; 30839; -.
DR Ensembl; ENSMUST00000015239; ENSMUSP00000015239; ENSMUSG00000015095. [Q9QXW2-1]
DR GeneID; 30839; -.
DR KEGG; mmu:30839; -.
DR UCSC; uc008isj.1; mouse. [Q9QXW2-1]
DR UCSC; uc008isk.1; mouse. [Q9QXW2-2]
DR CTD; 54461; -.
DR MGI; MGI:1354731; Fbxw5.
DR VEuPathDB; HostDB:ENSMUSG00000015095; -.
DR eggNOG; ENOG502QTGQ; Eukaryota.
DR GeneTree; ENSGT00730000111276; -.
DR HOGENOM; CLU_021121_0_0_1; -.
DR InParanoid; Q9QXW2; -.
DR OMA; LYKFYNR; -.
DR OrthoDB; 771384at2759; -.
DR PhylomeDB; Q9QXW2; -.
DR TreeFam; TF324320; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 30839; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Fbxw5; mouse.
DR PRO; PR:Q9QXW2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9QXW2; protein.
DR Bgee; ENSMUSG00000015095; Expressed in spermatocyte and 239 other tissues.
DR ExpressionAtlas; Q9QXW2; baseline and differential.
DR Genevisible; Q9QXW2; MM.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR042508; FBXW5.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR20995; PTHR20995; 1.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..573
FT /note="F-box/WD repeat-containing protein 5"
FT /id="PRO_0000050993"
FT DOMAIN 3..49
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 90..129
FT /note="WD 1"
FT REPEAT 470..509
FT /note="WD 2"
FT REPEAT 511..551
FT /note="WD 3"
FT MOTIF 308..316
FT /note="D-box"
FT MOD_RES 151
FT /note="Phosphoserine; by PLK4"
FT /evidence="ECO:0000250|UniProtKB:Q969U6"
FT VAR_SEQ 1
FT /note="M -> MLSAVEFSGGQLVGLARTAMSGTPDYQSLPGVGDEEAWVQSRHWWVS
FT GPSGQNVTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042293"
FT VAR_SEQ 530..573
FT /note="LTASDDATIKAWRSPRIVRVLQAPRPRPRPRPRPFFSWFASHRR -> PDSQ
FT RRCHYQSLAFTTHCSCSAGSTPSPPPSPPPLLLLVCQP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042294"
SQ SEQUENCE 573 AA; 64646 MW; B71B3B207D3091B1 CRC64;
MDEGGLPLLP DSLVYQIFLS LGPADVLAAG LVCRQWQAVS RDEFLWKEQF YRYYQVARDV
PRHPAATSWY EEFRRLYDMV PCVEVQTLKE HTDQVLHLSF SHSGYQFASC SKDCTVKIWN
NDLTISLLHS ADMRPYNWSY TQFSQFNQDD SLLLASGVFL GPHNSSSGEI AVISLDSFAL
LSRVRNKPYD VFGCWLTETS LISGNLHRIG DITSCSVLWL NNAFQDVESE NVNVVKRLFK
IQNLNASTIR TVMVADCSRF DSPDLLLDAS DQAGLPCRVF DLGGDTEEEA TDPGLHTSGS
DHVKKGLRRV FDSVLDGHGQ LSDCALETKV AELLAQGHTK PPECNDADTR NKYLIFTTGC
LTYSPHQIGI KQILPHQMTT AGPVLGEGRG SDAFFDALDH VIDVHGHIIG MGLSPDNRYL
YVNSRAWPPG SVVADPMQPP PIAEEIDLLV FDLKTMREVK RALRAHRAYT PNDECFFIFL
DVSRDFVASG AEDRHGYIWD RHYNICLAKL RHEDVVNSVA FSPQEQELLL TASDDATIKA
WRSPRIVRVL QAPRPRPRPR PRPFFSWFAS HRR
