FXL17_MOUSE
ID FXL17_MOUSE Reviewed; 701 AA.
AC Q9QZN1; B2RRC1; Q8BTC3;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=F-box/LRR-repeat protein 17 {ECO:0000303|PubMed:27234298};
DE AltName: Full=F-box and leucine-rich repeat protein 17 {ECO:0000305};
DE AltName: Full=F-box only protein 13 {ECO:0000303|PubMed:10531037};
GN Name=Fbxl17 {ECO:0000303|PubMed:27234298, ECO:0000312|MGI:MGI:1354704};
GN Synonyms=Fbl17, Fbx13 {ECO:0000303|PubMed:10531037}, Fbxo13;
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].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 240-674 (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 568-701 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J;
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 [5]
RP FUNCTION.
RX PubMed=27234298; DOI=10.15252/embj.201593374;
RA Raducu M., Fung E., Serres S., Infante P., Barberis A., Fischer R.,
RA Bristow C., Thezenas M.L., Finta C., Christianson J.C., Buffa F.M.,
RA Kessler B.M., Sibson N.R., Di Marcotullio L., Toftgaard R.,
RA D'Angiolella V.;
RT "SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and
RT medulloblastoma development.";
RL EMBO J. 35:1400-1416(2016).
RN [6]
RP FUNCTION, AND INTERACTION WITH PRMT1.
RX PubMed=28883095; DOI=10.1242/jcs.206904;
RA Lai Y., Li J., Li X., Zou C.;
RT "Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via
RT an SCFFbxl17-recognized acetyldegron.";
RL J. Cell Sci. 130:3578-3587(2017).
CC -!- FUNCTION: Substrate-recognition component of the SCF(FBXL17) E3
CC ubiquitin ligase complex, a key component of a quality control pathway
CC required to ensure functional dimerization of BTB domain-containing
CC proteins (dimerization quality control, DQC). FBXL17 specifically
CC recognizes and binds a conserved degron of non-consecutive residues
CC present at the interface of BTB dimers of aberrant composition:
CC aberrant BTB dimer are then ubiquitinated by the SCF(FBXL17) complex
CC and degraded by the proteasome (By similarity). The ability of the
CC SCF(FBXL17) complex to eliminate compromised BTB dimers is required for
CC the differentiation and survival of neural crest and neuronal cells (By
CC similarity). The SCF(FBXL17) complex mediates ubiquitination and
CC degradation of BACH1 (By similarity). The SCF(FBXL17) complex is also
CC involved in the regulation of the hedgehog/smoothened (Hh) signaling
CC pathway by mediating the ubiquitination and degradation of SUFU,
CC allowing the release of GLI1 from SUFU for proper Hh signal
CC transduction (PubMed:27234298). The SCF(FBXL17) complex mediates
CC ubiquitination and degradation of PRMT1 (PubMed:28883095).
CC {ECO:0000250|UniProtKB:B1H1X1, ECO:0000250|UniProtKB:Q9UF56,
CC ECO:0000269|PubMed:27234298, ECO:0000269|PubMed:28883095}.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXL17) composed of CUL1, SKP1, RBX1 and FBXL17. Interacts
CC with BTB domain-containing proteins such as KLHL12, BCL6 and BACH1;
CC specifically recognizes and binds a conserved degron of non-consecutive
CC residues present at the interface of BTB dimers of aberrant
CC composition. Interacts with SUFU (By similarity). Interacts with PRMT1
CC (PubMed:28883095). {ECO:0000250|UniProtKB:Q9UF56,
CC ECO:0000269|PubMed:28883095}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UF56}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UF56}. Note=Present in the cytoplasm and
CC nucleus; more abundant in the cytoplasm.
CC {ECO:0000250|UniProtKB:Q9UF56}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QZN1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QZN1-2; Sequence=VSP_009477, VSP_009478;
CC -!- SIMILARITY: Belongs to the FBXL17 family. {ECO:0000305}.
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DR EMBL; CH466537; EDL38277.1; -; Genomic_DNA.
DR EMBL; BC058120; AAH58120.1; -; mRNA.
DR EMBL; BC138330; AAI38331.1; -; mRNA.
DR EMBL; BC138331; AAI38332.1; -; mRNA.
DR EMBL; AF176529; AAF09138.1; -; mRNA.
DR EMBL; AK004419; BAC25082.1; -; mRNA.
DR CCDS; CCDS50162.1; -. [Q9QZN1-1]
DR RefSeq; NP_056609.1; NM_015794.1. [Q9QZN1-1]
DR AlphaFoldDB; Q9QZN1; -.
DR SMR; Q9QZN1; -.
DR BioGRID; 206092; 1.
DR STRING; 10090.ENSMUSP00000024761; -.
DR iPTMnet; Q9QZN1; -.
DR PhosphoSitePlus; Q9QZN1; -.
DR EPD; Q9QZN1; -.
DR MaxQB; Q9QZN1; -.
DR PaxDb; Q9QZN1; -.
DR PeptideAtlas; Q9QZN1; -.
DR PRIDE; Q9QZN1; -.
DR ProteomicsDB; 271817; -. [Q9QZN1-1]
DR ProteomicsDB; 271818; -. [Q9QZN1-2]
DR Antibodypedia; 25280; 128 antibodies from 18 providers.
DR DNASU; 50758; -.
DR Ensembl; ENSMUST00000024761; ENSMUSP00000024761; ENSMUSG00000023965. [Q9QZN1-1]
DR GeneID; 50758; -.
DR KEGG; mmu:50758; -.
DR UCSC; uc008dfj.2; mouse. [Q9QZN1-2]
DR UCSC; uc008dfl.2; mouse. [Q9QZN1-1]
DR CTD; 64839; -.
DR MGI; MGI:1354704; Fbxl17.
DR VEuPathDB; HostDB:ENSMUSG00000023965; -.
DR eggNOG; KOG1947; Eukaryota.
DR GeneTree; ENSGT00940000156973; -.
DR HOGENOM; CLU_024577_3_0_1; -.
DR InParanoid; Q9QZN1; -.
DR OMA; KLGANCR; -.
DR OrthoDB; 524674at2759; -.
DR PhylomeDB; Q9QZN1; -.
DR TreeFam; TF332421; -.
DR Reactome; R-MMU-9708530; Regulation of BACH1 activity.
DR BioGRID-ORCS; 50758; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Fbxl17; mouse.
DR PRO; PR:Q9QZN1; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9QZN1; protein.
DR Bgee; ENSMUSG00000023965; Expressed in cumulus cell and 229 other tissues.
DR ExpressionAtlas; Q9QZN1; baseline and differential.
DR Genevisible; Q9QZN1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR GO; GO:0014033; P:neural crest cell differentiation; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF13516; LRR_6; 1.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 11.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..701
FT /note="F-box/LRR-repeat protein 17"
FT /id="PRO_0000119866"
FT DOMAIN 318..365
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REGION 73..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..92
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..250
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..474
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009477"
FT VAR_SEQ 475..502
FT /note="YKISDEGMIVIAKSCLKLQRIYMQENKL -> MDPFGFVLLDKEGMKYEKTQ
FT TKKPGKAK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009478"
SQ SEQUENCE 701 AA; 75683 MW; 314208800D0063CC CRC64;
MGHLLSKEPR NRPSQKRPRC CSWCRRRRPL LRLPRRALAK ASPQPAAPRS RDCFFRGPCM
LCFIVHSPGA PASAGLEEEP PLSPPPPPPR DGAYAAVSSQ HLARRYAALA AEDCAAAARR
FLLSSAAAAA AAASSPASCC KELGLAAAAA WEQQGRSLFL AGVGPVRFLG PLAAVQLFRA
PPAPPPQAEP ATALEMVCKR KGAGVPACTP CKQPRCGCGG CGGGGGGGGG PAGGGASPPR
PPDAGCCQAP EQPPPPLCPA PASPASECAP IVAAAGDTVR AGGTAPSSAQ QQPESGDADC
QEPPENPCDC HREPPPEIPD INQLPPSILL KIFSNLSLNE RCLSASLVCK YWRDLCLDFQ
FWKQLDLSSR QQVTDELLEK IASRSQNIIE INISDCRSLS DSGVCVLAFK CPGLLRYTAY
RCKQLSDTSI IAVASHCPLL QKVHVGNQDK LTDEGLKQLG SRCRELKDIH FGQCYKISDE
GMIVIAKSCL KLQRIYMQEN KLVTDQSVKA FAEHCPELQY VGFMGCSVTS KGVIHLTKLR
NLSSLDLRHI TELDNETVME IVKRCKNLSS LNLCLNWIIN DRCVEVIAKE GQNLKELYLV
SCKITDYALI AIGRYSVTIE TVDVGWCKEI TDQGATLIAQ SSKSLRYLGL MRCDKVNELT
VEQLVQQYPH ITFSTVLQDC KRTLERAYQM GWTPNMSAAT S
