ID   FBXW5_RAT               Reviewed;         569 AA.
AC   Q4KLI9; F8WFL5;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   02-AUG-2005, sequence version 1.
DT   03-AUG-2022, entry version 121.
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;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
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]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Thymus;
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).
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 recognition component of the SCF(FBXW5) E3
CC       ubiquitin-protein ligase complex which mediates the ubiquitination and
CC       subsequent proteasomal degradation of SASS6 during S phase, leading to
CC       prevent centriole reduplication. The SCF(FBXW5) complex also mediates
CC       ubiquitination and degradation of actin-regulator EPS8 during G2 phase,
CC       leading to the transient degradation of EPS8 and subsequent cell shape
CC       changes required to allow mitotic progression. Substrate-specific
CC       adapter of the DCX(FBXW5) E3 ubiquitin-protein ligase complex which
CC       mediates the polyubiquitination and subsequent degradation of TSC2. May
CC       also act as a negative regulator of MAP3K7/TAK1 signaling in the
CC       interleukin-1B (IL1B) signaling pathway (By similarity). {ECO:0000250}.
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, EPS8, TSC1, TSC2
CC       and SASS6.Interacts with TNFAIP8L1; TNFAIP8L1 competes with TSC2 to
CC       bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.
CC       {ECO:0000250, ECO:0000250|UniProtKB:Q9QXW2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q969U6}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q4KLI9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q4KLI9-2; Sequence=VSP_042295;
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}.
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DR   EMBL; BC099179; AAH99179.1; -; mRNA.
DR   RefSeq; NP_001020901.1; NM_001025730.2. [Q4KLI9-1]
DR   RefSeq; XP_006233685.1; XM_006233623.2. [Q4KLI9-2]
DR   RefSeq; XP_006233686.1; XM_006233624.3. [Q4KLI9-1]
DR   RefSeq; XP_006233687.1; XM_006233625.2. [Q4KLI9-1]
DR   RefSeq; XP_006233688.1; XM_006233626.3. [Q4KLI9-1]
DR   RefSeq; XP_006233689.1; XM_006233627.2. [Q4KLI9-1]
DR   AlphaFoldDB; Q4KLI9; -.
DR   SMR; Q4KLI9; -.
DR   STRING; 10116.ENSRNOP00000049492; -.
DR   PhosphoSitePlus; Q4KLI9; -.
DR   PaxDb; Q4KLI9; -.
DR   Ensembl; ENSRNOT00000034089; ENSRNOP00000029229; ENSRNOG00000028674. [Q4KLI9-1]
DR   Ensembl; ENSRNOT00000113742; ENSRNOP00000078193; ENSRNOG00000028674. [Q4KLI9-2]
DR   GeneID; 362081; -.
DR   KEGG; rno:362081; -.
DR   UCSC; RGD:1305661; rat. [Q4KLI9-1]
DR   CTD; 54461; -.
DR   RGD; 1305661; Fbxw5.
DR   eggNOG; ENOG502QTGQ; Eukaryota.
DR   GeneTree; ENSGT00730000111276; -.
DR   HOGENOM; CLU_021121_0_0_1; -.
DR   InParanoid; Q4KLI9; -.
DR   OMA; LYKFYNR; -.
DR   OrthoDB; 771384at2759; -.
DR   Reactome; R-RNO-8951664; Neddylation.
DR   Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:Q4KLI9; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Bgee; ENSRNOG00000028674; Expressed in testis and 19 other tissues.
DR   Genevisible; Q4KLI9; RN.
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; ISS:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR   GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR   GO; GO:0007088; P:regulation of mitotic nuclear division; ISO:RGD.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS: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   2: Evidence at transcript level;
KW   Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW   Repeat; Ubl conjugation; Ubl conjugation pathway; WD repeat.
FT   CHAIN           1..569
FT                   /note="F-box/WD repeat-containing protein 5"
FT                   /id="PRO_0000292805"
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 -> MLSAMEFSAGQLVGLARTAMSGTPDHQSLPGVGGEEAWVESSHWWVS
FT                   GPSGQNVTM (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_042295"
SQ   SEQUENCE   569 AA;  64034 MW;  344C77FB90715728 CRC64;
     MDEGGMPLLP DSLVYQIFLS LGPADVLAAG LVCRQWQAVS RDEFLWREQF YRYYQVARDV
     PRHPAATSWY EEFRRLYDMV PCVEVQTLKE HTDQVLHLSF SHSGYQFASC SKDCTVKIWN
     NDLTISLLHS ADMRPYNWSY TQFSQFNQDD SLLLASGVFL GPHNSSSGEI AVISLDSFAL
     LSRVRNKPYD VFGCWLTETS LISGNLHRIG DVTSCSVLWL NNAFQDVESE NVNVVKRLFK
     IQNLNASTIR TVMVADCSRF DSPDLLLDAG DQAGLPCRVF DLGGDTEEEA TDPGLHTSGS
     GHVKEGLRRV FDSVLDGHGQ LSDCALETKV AELLAQGHTK PPECPDADSR NKYLIFTTGC
     LTYSPHQIGI KQILPHQMTT AGPVLGEGRG SDAFFDALDH VIDVHGHIIG MGLSPDNRYL
     YVNSRAWPPG SVVADPMQPP PIAEEIDLLV FDLKTMREVK RALRAHRAYT PNDECFFIFL
     DVSRDFVASG AEDRHGYIWD RHYNICLAKL RHEDVVNSVA FSPQEQELLL TASDDATIKA
     WRSPRIVRVL QAPHPRPRPF FSWFASHRR