FBXW8_RAT
ID FBXW8_RAT Reviewed; 596 AA.
AC P0DL28;
DT 01-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 1.
DT 03-AUG-2022, entry version 51.
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 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 FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=21572988; DOI=10.1371/journal.pbio.1001060;
RA Litterman N., Ikeuchi Y., Gallardo G., O'Connell B.C., Sowa M.E.,
RA Gygi S.P., Harper J.W., Bonni A.;
RT "An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi
RT morphology and dendrite patterning.";
RL PLoS Biol. 9:E1001060-E1001060(2011).
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 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). The Cul7-RING(FBXW8)
CC complex mediates ubiquitination and consequent degradation of GORASP1,
CC acting as a component of the ubiquitin ligase pathway that regulates
CC Golgi morphogenesis and dendrite patterning in brain.
CC {ECO:0000250|UniProtKB:Q8N3Y1, ECO:0000269|PubMed:21572988}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF-like complex consisting of CUL7, RBX1, SKP1,
CC FBXW8 and GLMN isoform 1. Interacts with CUL7. Interacts with OBSL1,
CC CUL1, CUL2, SKP1, CCT6B, PFDN5, CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8,
CC ARF1, TRIP13, and PDCD5. Interacts with MAP4K1/HPK1 (when
CC autophosphorylated). Associated component of the 3M complex (By
CC similarity). Interacts with GORASP1. Interacts with POUF51 (when
CC phosphorylated on 'Ser-347') (By similarity).
CC {ECO:0000250|UniProtKB:Q8BIA4, ECO:0000250|UniProtKB:Q8N3Y1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:21572988}. Golgi apparatus
CC {ECO:0000269|PubMed:21572988}. Note=Colocalizes with CUL7 at the Golgi
CC apparatus in neurons.
CC -!- TISSUE SPECIFICITY: Expressed in placenta and embryonic brain (at
CC protein level). {ECO:0000269|PubMed:21572988}.
CC -!- DEVELOPMENTAL STAGE: In cerebellum, abundantly expressed during the
CC first two postnatal weeks, with levels decreasing thereafter. In
CC primary granule neurons, highly expressed at postnatal day 6 (P6), with
CC levels decreasing with neuron maturation (at protein level).
CC {ECO:0000269|PubMed:21572988}.
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DR EMBL; AABR06072298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DL28; -.
DR SMR; P0DL28; -.
DR CORUM; P0DL28; -.
DR STRING; 10116.ENSRNOP00000059618; -.
DR PaxDb; P0DL28; -.
DR RGD; 1306032; Fbxw8.
DR VEuPathDB; HostDB:ENSRNOG00000001126; -.
DR eggNOG; KOG0274; Eukaryota.
DR InParanoid; P0DL28; -.
DR OMA; VFQECRA; -.
DR PhylomeDB; P0DL28; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:P0DL28; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001126; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; P0DL28; baseline and differential.
DR Genevisible; P0DL28; RN.
DR GO; GO:1990393; C:3M complex; IEA:Ensembl.
DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISO:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0060712; P:spongiotrophoblast layer development; ISO:RGD.
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; Cytoplasm; Golgi apparatus; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..596
FT /note="F-box/WD repeat-containing protein 8"
FT /id="PRO_0000422124"
FT DOMAIN 111..157
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 195..243
FT /note="WD 1"
FT REPEAT 251..292
FT /note="WD 2"
FT REPEAT 295..334
FT /note="WD 3"
FT REPEAT 428..468
FT /note="WD 4"
FT REPEAT 471..508
FT /note="WD 5"
FT REGION 21..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..95
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 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BIA4"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BIA4"
SQ SEQUENCE 596 AA; 67819 MW; A198BC5838DB4A4B CRC64;
MEDHNLEEFR QRWQEELAHS QVLRRRRRLE AGERRPRRPE AGARGEPASG YLGLAQGLLE
GAGRPPAPRP GRTDRKDVSS RSRSPPDRDA AEPEPLVDQL IRDLNEMDDV PFFDVHLPYE
LAINIFQYLN RRELGLCAQV SKTWKVIAED EVLWYRLCRQ EGHLPHSRFS DYTCWKLILQ
ECLAPVHLIR PSWMNRKGAV SELEHVPDAV LCDVRSHDGV VIAGYTSGEV RVWDTRTWDY
VAPFLESESE EEDPGMQPYV SFVRINSSLA VAAYEDGILN VWDLRTGRFP IFRFEHDARI
QALALSQEKP VVATASAFDV VMLYPNEEGN WHVASEFEVQ KLVDYLEIVP NTGRYPVAIA
TAGDLVYLLK AEDSARTLHY VYGQPATCLD VSASQVAFGV KSLGWVYEGN KILVYSLEAE
RCLSKLGNAL GDFTCVNIRD SPPNLMVSGN MDRRVRLHDL RTDKIALSLS AHQLGVSAVQ
MDDWKIVSGG EEGLVSVWDY RMNQKLWEVH SRHPVRYISF NSHSLITANV PYEKVLRNSD
LDNFACHRRH RGLIHAYEFA VDQLAFQSPL PICRLPRDTV AGYSYDLALS FPYDSI
