FBX2_MOUSE
ID FBX2_MOUSE Reviewed; 297 AA.
AC Q80UW2; Q8R0D2;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=F-box only protein 2;
GN Name=Fbxo2; Synonyms=Fbs1, Fbx2;
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].
RC STRAIN=FVB/N-3; TISSUE=Eye, and Mammary tumor;
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 [2]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12140560; DOI=10.1038/nature00890;
RA Yoshida Y., Chiba T., Tokunaga F., Kawasaki H., Iwai K., Suzuki T., Ito Y.,
RA Matsuoka K., Yoshida M., Tanaka K., Tai T.;
RT "E3 ubiquitin ligase that recognizes sugar chains.";
RL Nature 418:438-442(2002).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VCP.
RX PubMed=15723043; DOI=10.1038/sj.embor.7400351;
RA Yoshida Y., Adachi E., Fukiya K., Iwai K., Tanaka K.;
RT "Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded
RT substrates.";
RL EMBO Rep. 6:239-244(2005).
RN [4]
RP FUNCTION, AND NMR SPECTROSCOPY.
RX PubMed=17720138; DOI=10.1016/j.bbrc.2007.08.056;
RA Yamaguchi Y., Hirao T., Sakata E., Kamiya Y., Kurimoto E., Yoshida Y.,
RA Suzuki T., Tanaka K., Kato K.;
RT "Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-
RT glycanase.";
RL Biochem. Biophys. Res. Commun. 362:712-716(2007).
RN [5]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17215248; DOI=10.1074/jbc.m611168200;
RA Yoshida Y., Murakami A., Iwai K., Tanaka K.;
RT "A neural-specific F-box protein Fbs1 functions as a chaperone suppressing
RT glycoprotein aggregation.";
RL J. Biol. Chem. 282:7137-7144(2007).
RN [6]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH SKP1, AND
RP TISSUE SPECIFICITY.
RX PubMed=17494702; DOI=10.1523/jneurosci.0206-07.2007;
RA Nelson R.F., Glenn K.A., Zhang Y., Wen H., Knutson T., Gouvion C.M.,
RA Robinson B.K., Zhou Z., Yang B., Smith R.J., Paulson H.L.;
RT "Selective cochlear degeneration in mice lacking the F-box protein, Fbx2, a
RT glycoprotein-specific ubiquitin ligase subunit.";
RL J. Neurosci. 27:5163-5171(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Kidney;
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 117-297 IN COMPLEX WITH
RP CHITOBIOSE, FUNCTION, AND MUTAGENESIS OF PHE-177; TYR-279; TRP-280 AND
RP LYS-281.
RX PubMed=14990996; DOI=10.1038/nsmb732;
RA Mizushima T., Hirao T., Yoshida Y., Lee S.J., Chiba T., Iwai K.,
RA Yamaguchi Y., Kato K., Tsukihara T., Tanaka K.;
RT "Structural basis of sugar-recognizing ubiquitin ligase.";
RL Nat. Struct. Mol. Biol. 11:365-370(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEXES WITH SKP1 AND
RP GLYCOPROTEIN SUBSTRATE RNASE1.
RX PubMed=17389369; DOI=10.1073/pnas.0610312104;
RA Mizushima T., Yoshida Y., Kumanomidou T., Hasegawa Y., Suzuki A.,
RA Yamane T., Tanaka K.;
RT "Structural basis for the selection of glycosylated substrates by SCF(Fbs1)
RT ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5777-5781(2007).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex that mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. Involved in the endoplasmic reticulum-associated degradation
CC pathway (ERAD) for misfolded lumenal proteins by recognizing and
CC binding sugar chains on unfolded glycoproteins that are
CC retrotranslocated into the cytosol and promoting their ubiquitination
CC and subsequent degradation. Prevents formation of cytosolic aggregates
CC of unfolded glycoproteins that have been retrotranslocated into the
CC cytosol. Able to recognize and bind denatured glycoproteins,
CC preferentially those of the high-mannose type.
CC {ECO:0000269|PubMed:12140560, ECO:0000269|PubMed:14990996,
CC ECO:0000269|PubMed:15723043, ECO:0000269|PubMed:17215248,
CC ECO:0000269|PubMed:17720138}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the SCF(FBXO2) complex consisting of CUL1, RBX1,
CC SKP1 and FBXO2. Predominantly detected as heterodimer with SKP1; the
CC heterodimer with SKP1 is not part of the SCF(FBXO2) complex.
CC {ECO:0000269|PubMed:12140560, ECO:0000269|PubMed:14990996,
CC ECO:0000269|PubMed:17215248}.
CC -!- INTERACTION:
CC Q80UW2; P61823: RNASE1; Xeno; NbExp=2; IntAct=EBI-2314714, EBI-908364;
CC Q80UW2; P63208-1: SKP1; Xeno; NbExp=4; IntAct=EBI-2314714, EBI-307497;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Microsome membrane; Peripheral
CC membrane protein; Cytoplasmic side.
CC -!- TISSUE SPECIFICITY: Detected in brain and cochlea, in epithelial
CC support cells and hair cells of the organ of Corti (at protein level).
CC {ECO:0000269|PubMed:17215248, ECO:0000269|PubMed:17494702}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth. Mice are viable
CC and fertile, but after two to four months, gradual hearing loss sets
CC in, due to degeneration of epithelial support cells and hair cells of
CC the organ of Corti and spiral ganglion neurodegeneration.
CC {ECO:0000269|PubMed:17494702}.
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DR EMBL; BC027053; AAH27053.1; -; mRNA.
DR EMBL; BC046586; AAH46586.1; -; mRNA.
DR CCDS; CCDS18935.1; -.
DR RefSeq; NP_789818.1; NM_176848.1.
DR RefSeq; XP_006538877.1; XM_006538814.3.
DR PDB; 1UMH; X-ray; 2.00 A; A=117-297.
DR PDB; 1UMI; X-ray; 2.40 A; A=117-297.
DR PDB; 2E31; X-ray; 2.40 A; A=1-297.
DR PDB; 2E32; X-ray; 3.52 A; A/C=1-297.
DR PDB; 2E33; X-ray; 2.70 A; A=105-297.
DR PDB; 2RJ2; X-ray; 1.70 A; A=117-297.
DR PDB; 5B4N; X-ray; 2.30 A; A/B=117-297.
DR PDBsum; 1UMH; -.
DR PDBsum; 1UMI; -.
DR PDBsum; 2E31; -.
DR PDBsum; 2E32; -.
DR PDBsum; 2E33; -.
DR PDBsum; 2RJ2; -.
DR PDBsum; 5B4N; -.
DR AlphaFoldDB; Q80UW2; -.
DR SMR; Q80UW2; -.
DR BioGRID; 231053; 14.
DR CORUM; Q80UW2; -.
DR DIP; DIP-54758N; -.
DR IntAct; Q80UW2; 5.
DR STRING; 10090.ENSMUSP00000037377; -.
DR UniLectin; Q80UW2; -.
DR iPTMnet; Q80UW2; -.
DR PhosphoSitePlus; Q80UW2; -.
DR SwissPalm; Q80UW2; -.
DR EPD; Q80UW2; -.
DR MaxQB; Q80UW2; -.
DR PaxDb; Q80UW2; -.
DR PRIDE; Q80UW2; -.
DR ProteomicsDB; 272964; -.
DR Antibodypedia; 28127; 204 antibodies from 30 providers.
DR DNASU; 230904; -.
DR Ensembl; ENSMUST00000047951; ENSMUSP00000037377; ENSMUSG00000041556.
DR GeneID; 230904; -.
DR KEGG; mmu:230904; -.
DR UCSC; uc008vuk.1; mouse.
DR CTD; 26232; -.
DR MGI; MGI:2446216; Fbxo2.
DR VEuPathDB; HostDB:ENSMUSG00000041556; -.
DR eggNOG; ENOG502QS9C; Eukaryota.
DR GeneTree; ENSGT00940000160929; -.
DR HOGENOM; CLU_068548_0_0_1; -.
DR InParanoid; Q80UW2; -.
DR OMA; YEWCRKA; -.
DR OrthoDB; 922544at2759; -.
DR PhylomeDB; Q80UW2; -.
DR TreeFam; TF320527; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 230904; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Fbxo2; mouse.
DR EvolutionaryTrace; Q80UW2; -.
DR PRO; PR:Q80UW2; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80UW2; protein.
DR Bgee; ENSMUSG00000041556; Expressed in vestibular membrane of cochlear duct and 109 other tissues.
DR ExpressionAtlas; Q80UW2; baseline and differential.
DR Genevisible; Q80UW2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:MGI.
DR GO; GO:0030246; F:carbohydrate binding; IDA:MGI.
DR GO; GO:0006516; P:glycoprotein catabolic process; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:MGI.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR InterPro; IPR007397; F-box-assoc_dom.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR039752; F-box_only.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR PANTHER; PTHR12125; PTHR12125; 1.
DR Pfam; PF00646; F-box; 1.
DR Pfam; PF04300; FBA; 1.
DR SMART; SM01198; FBA; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS51114; FBA; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Lectin; Membrane;
KW Microsome; Phosphoprotein; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..297
FT /note="F-box only protein 2"
FT /id="PRO_0000119876"
FT DOMAIN 48..95
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 117..297
FT /note="FBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00482"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..47
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 214..216
FT /ligand="a carbohydrate"
FT /ligand_id="ChEBI:CHEBI:16646"
FT BINDING 279..280
FT /ligand="a carbohydrate"
FT /ligand_id="ChEBI:CHEBI:16646"
FT SITE 159
FT /note="Important for carbohydrate binding"
FT SITE 177
FT /note="Important for carbohydrate binding"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 177
FT /note="F->A: Abolishes binding of glycoprotein targets."
FT /evidence="ECO:0000269|PubMed:14990996"
FT MUTAGEN 279
FT /note="Y->A: Abolishes binding of glycoprotein targets."
FT /evidence="ECO:0000269|PubMed:14990996"
FT MUTAGEN 280
FT /note="W->A: Abolishes binding of glycoprotein targets.
FT Strongly reduced ubiquitination of glycoprotein targets."
FT /evidence="ECO:0000269|PubMed:14990996"
FT MUTAGEN 281
FT /note="K->A: No effect on carbohydrate binding."
FT /evidence="ECO:0000269|PubMed:14990996"
FT HELIX 56..64
FT /evidence="ECO:0007829|PDB:2E31"
FT HELIX 68..73
FT /evidence="ECO:0007829|PDB:2E31"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:2E31"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:2E31"
FT HELIX 89..98
FT /evidence="ECO:0007829|PDB:2E31"
FT HELIX 116..123
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:5B4N"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2RJ2"
FT TURN 134..139
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:2RJ2"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:1UMH"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:2RJ2"
FT TURN 188..192
FT /evidence="ECO:0007829|PDB:2RJ2"
FT HELIX 195..200
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 204..212
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 219..229
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 265..278
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:2RJ2"
FT STRAND 287..296
FT /evidence="ECO:0007829|PDB:2RJ2"
SQ SEQUENCE 297 AA; 33676 MW; E0F8A5601CE5930C CRC64;
MDGDGDPESV SHPEEASPEE QPEEAGAEAS AEEEQLREAE EEEEAEAVEY LAELPEPLLL
RVLAELPATE LVQACRLVCL RWKELVDGAP LWLLKCQQEG LVPEGSADEE RDHWQQFYFL
SKRRRNLLRN PCGEEDLEGW SDVEHGGDGW RVEELPGDNG VEFTQDDSVK KYFASSFEWC
RKAQVIDLQA EGYWEELLDT TQPAIVVKDW YSGRTDAGSL YELTVRLLSE NEDVLAEFAT
GQVAVPEDGS WMEISHTFID YGPGVRFVRF EHGGQDSVYW KGWFGARVTN SSVWVEP
