FBXW8_MOUSE
ID FBXW8_MOUSE Reviewed; 598 AA.
AC Q8BIA4; Q8BI62; Q8BI75; Q8BI76; Q8CID8; Q921Z1;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=F-box/WD repeat-containing protein 8;
DE AltName: Full=F-box and WD-40 domain-containing protein 8;
GN Name=Fbxw8;
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 MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Corpus striatum, Diencephalon, and Eye;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Liver, and Mammary gland;
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 INTERACTION WITH CUL7.
RX PubMed=16880526; DOI=10.1128/mcb.00595-06;
RA Tsunematsu R., Nishiyama M., Kotoshiba S., Saiga T., Kamura T.,
RA Nakayama K.I.;
RT "Fbxw8 is essential for Cul1-Cul7 complex formation and for placental
RT development.";
RL Mol. Cell. Biol. 26:6157-6169(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17998335; DOI=10.1128/mcb.01665-07;
RA Tsutsumi T., Kuwabara H., Arai T., Xiao Y., Decaprio J.A.;
RT "Disruption of the Fbxw8 gene results in pre- and postnatal growth
RT retardation in mice.";
RL Mol. Cell. Biol. 28:743-751(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84 AND SER-86, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and 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 INTERACTION WITH POUF51.
RX PubMed=29153991; DOI=10.1016/j.stemcr.2017.10.017;
RA Bae K.B., Yu D.H., Lee K.Y., Yao K., Ryu J., Lim D.Y., Zykova T.A.,
RA Kim M.O., Bode A.M., Dong Z.;
RT "Serine 347 Phosphorylation by JNKs Negatively Regulates OCT4 Protein
RT Stability in Mouse Embryonic Stem Cells.";
RL Stem Cell Reports 9:2050-2064(2017).
CC -!- FUNCTION: Substrate-recognition component of a Cul7-RING ubiquitin-
CC protein ligase complex, which mediates the ubiquitination and
CC subsequent proteasomal degradation of target proteins. The Cul7-
CC RING(FBXW8) complex mediates ubiquitination and consequent degradation
CC of GORASP1, acting as a component of the ubiquitin ligase pathway that
CC regulates Golgi morphogenesis and dendrite patterning in brain. The
CC Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1:
CC recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its
CC degradation, thereby affecting cell proliferation and differentiation.
CC Associated component of the 3M complex, suggesting that it mediates
CC some of 3M complex functions (By similarity).
CC {ECO:0000250|UniProtKB:Q8N3Y1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF-like complex consisting of CUL7, RBX1, SKP1,
CC FBXW8 and GLMN. Interacts with OBSL1, CUL1, CUL2, SKP1, CCT6B, PFDN5,
CC CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1.
CC Interacts with MAP4K1/HPK1 (when autophosphorylated). Associated
CC component of the 3M complex (By similarity). Interacts with CUL7.
CC Interacts with POUF51 (when phosphorylated on 'Ser-347')
CC (PubMed:29153991). {ECO:0000250, ECO:0000269|PubMed:16880526,
CC ECO:0000269|PubMed:29153991}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P0DL28}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P0DL28}. Note=Colocalizes with CUL7 at the Golgi
CC apparatus in neurons. {ECO:0000250|UniProtKB:P0DL28}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BIA4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BIA4-4; Sequence=VSP_008502;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC skeletal muscle, cartilage and lung. {ECO:0000269|PubMed:17998335}.
CC -!- DISRUPTION PHENOTYPE: Reduced embryo size and neonatal lethality.
CC Embryos and placentas are smaller and only a third of the expected
CC number of mice survived birth. Mice that survive remain smaller
CC throughout postnatal development. {ECO:0000269|PubMed:17998335}.
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DR EMBL; AK034447; BAC28712.1; -; mRNA.
DR EMBL; AK047695; BAC33128.1; -; mRNA.
DR EMBL; AK047756; BAC33147.1; -; mRNA.
DR EMBL; AK053794; BAC35527.1; -; mRNA.
DR EMBL; BC009095; AAH09095.2; -; mRNA.
DR EMBL; BC024091; AAH24091.1; -; mRNA.
DR CCDS; CCDS19609.1; -. [Q8BIA4-1]
DR RefSeq; NP_766309.2; NM_172721.2. [Q8BIA4-1]
DR AlphaFoldDB; Q8BIA4; -.
DR SMR; Q8BIA4; -.
DR BioGRID; 231155; 10.
DR CORUM; Q8BIA4; -.
DR STRING; 10090.ENSMUSP00000047012; -.
DR iPTMnet; Q8BIA4; -.
DR PhosphoSitePlus; Q8BIA4; -.
DR EPD; Q8BIA4; -.
DR MaxQB; Q8BIA4; -.
DR PaxDb; Q8BIA4; -.
DR PeptideAtlas; Q8BIA4; -.
DR PRIDE; Q8BIA4; -.
DR ProteomicsDB; 267722; -. [Q8BIA4-1]
DR ProteomicsDB; 267723; -. [Q8BIA4-4]
DR Antibodypedia; 31322; 146 antibodies from 20 providers.
DR DNASU; 231672; -.
DR Ensembl; ENSMUST00000049474; ENSMUSP00000047012; ENSMUSG00000032867. [Q8BIA4-1]
DR GeneID; 231672; -.
DR KEGG; mmu:231672; -.
DR UCSC; uc008zge.1; mouse. [Q8BIA4-1]
DR CTD; 26259; -.
DR MGI; MGI:1923041; Fbxw8.
DR VEuPathDB; HostDB:ENSMUSG00000032867; -.
DR eggNOG; KOG0274; Eukaryota.
DR GeneTree; ENSGT00390000017221; -.
DR HOGENOM; CLU_024087_1_0_1; -.
DR InParanoid; Q8BIA4; -.
DR OMA; VFQECRA; -.
DR OrthoDB; 1046098at2759; -.
DR PhylomeDB; Q8BIA4; -.
DR TreeFam; TF332593; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 231672; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q8BIA4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BIA4; protein.
DR Bgee; ENSMUSG00000032867; Expressed in ear vesicle and 249 other tissues.
DR Genevisible; Q8BIA4; MM.
DR GO; GO:1990393; C:3M complex; ISO:MGI.
DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IPI:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0060712; P:spongiotrophoblast layer development; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IC:MGI.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Golgi apparatus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation pathway;
KW WD repeat.
FT CHAIN 1..598
FT /note="F-box/WD repeat-containing protein 8"
FT /id="PRO_0000050998"
FT DOMAIN 113..159
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 197..245
FT /note="WD 1"
FT REPEAT 253..294
FT /note="WD 2"
FT REPEAT 297..336
FT /note="WD 3"
FT REPEAT 430..470
FT /note="WD 4"
FT REPEAT 473..510
FT /note="WD 5"
FT REGION 20..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 71..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8N3Y1"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 457..598
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008502"
FT CONFLICT 67
FT /note="P -> T (in Ref. 1; BAC28712)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="F -> S (in Ref. 2; AAH09095)"
FT /evidence="ECO:0000305"
FT CONFLICT 247..248
FT /note="LE -> WS (in Ref. 1; BAC33128)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="I -> V (in Ref. 1; BAC35527)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 598 AA; 67956 MW; 4FEAF1C4384D3CA5 CRC64;
MDDHNLEEFR RHWQEELAQS QALRRRRRLE AGERRSPRRP EAGARGEPAS GYLGLAQGLL
EGAGRPPAPR PGRGGDRKDT SSRSRSPPDR DATEPEPLVD QLIRDLNELD DVPFFDVRLP
YELAINIFQY LNRRELGLCA QVSKTWKVIA EDEVLWYRLC RQEGHLPHSR FSDYTCWKLI
LQECLAKEHT LRANWKNRKG AVSELEHVPD AVLCDVRSHD GVVIAGYTSG DVRVWDTRTW
DYVAPFLESE SEEEDPGMQP YVSFVRINSS LAVAAYEDGI LNIWDLRTGR FPIFRFEHDA
RIQALALSQE KPIVATASAF DVVMLYPNEE GHWHVASEFE VQKLVDYLEI VPNTGRYPVA
IATAGDLVYL LKADDSARTL HYVYGQPATC LDVSASQVAF GVKSLGWVYE GNKILVYSLE
AERCLSKLGN ALGDFTCVNI RDSPPNLMVS GNMDRRVRIH DLRSDKIALS LSAHQLGVSA
VQMDDWKVVS GGEEGLVSVW DYRMNQKLWE VHSRHPVRYL SFNSHSLITA NVPYEKVLRN
SDLDNFACHR RHRGLIHAYE FAVDQLAFQS PLPVCRLPRD IMAGYSYDLA LSFPHDSI
