FBX3_HUMAN
ID FBX3_HUMAN Reviewed; 471 AA.
AC Q9UK99; B3KY16; D3DR05; Q86X90; Q9H0V2; Q9NUX2;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=F-box only protein 3;
GN Name=FBXO3; Synonyms=FBX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [6]
RP FUNCTION, INTERACTION WITH CUL1; PML; RBX1 AND SKP1, AND UBIQUITINATION OF
RP HIPK2.
RX PubMed=18809579; DOI=10.1128/mcb.00897-08;
RA Shima Y., Shima T., Chiba T., Irimura T., Pandolfi P.P., Kitabayashi I.;
RT "PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-
RT mediated degradation.";
RL Mol. Cell. Biol. 28:7126-7138(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-471 (ISOFORM 2).
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INTERACTION WITH RIFT VALLEY FEVER VIRUS NSS (MICROBIAL INFECTION).
RX PubMed=24403578; DOI=10.1128/jvi.02914-13;
RA Kainulainen M., Habjan M., Hubel P., Busch L., Lau S., Colinge J.,
RA Superti-Furga G., Pichlmair A., Weber F.;
RT "Virulence factor NSs of rift valley fever virus recruits the F-box protein
RT FBXO3 to degrade subunit p62 of general transcription factor TFIIH.";
RL J. Virol. 88:3464-3473(2014).
CC -!- FUNCTION: Substrate recognition component of the SCF (SKP1-CUL1-F-box
CC protein)-type E3 ubiquitin ligase complex. Mediates the ubiquitination
CC of HIPK2 and probably that of EP300, leading to rapid degradation by
CC the proteasome. In the presence of PML, HIPK2 ubiquitination still
CC occurs, but degradation is prevented. PML, HIPK2 and FBXO3 may act
CC synergically to activate p53/TP53-dependent transactivation.
CC {ECO:0000269|PubMed:18809579}.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex
CC consisting of FBXO3, SKP1, CUL1 and RBX1. Interacts with PML,
CC interaction is direct and takes place either alone or within the SCF
CC complex. {ECO:0000269|PubMed:18809579}.
CC -!- SUBUNIT: (Microbial infection) Isoform 1 and 2 interact with Rift
CC valley fever virus NSs; this interaction is important for GT2H1
CC degradation. {ECO:0000269|PubMed:24403578}.
CC -!- INTERACTION:
CC Q9UK99; Q13616: CUL1; NbExp=7; IntAct=EBI-2509901, EBI-359390;
CC Q9UK99; P63208: SKP1; NbExp=9; IntAct=EBI-2509901, EBI-307486;
CC Q9UK99; P04608: tat; Xeno; NbExp=3; IntAct=EBI-2509901, EBI-6164389;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with PML at the
CC peripheries of nuclear bodies.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UK99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UK99-2; Sequence=VSP_024395, VSP_024396;
CC Name=3;
CC IsoId=Q9UK99-3; Sequence=VSP_039614, VSP_024395, VSP_024396;
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK001943; BAA91991.1; -; mRNA.
DR EMBL; AK128454; BAG54678.1; -; mRNA.
DR EMBL; AL136625; CAB66560.1; -; mRNA.
DR EMBL; AC113192; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68186.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68188.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68189.1; -; Genomic_DNA.
DR EMBL; BC046110; AAH46110.1; -; mRNA.
DR EMBL; AF176702; AAF03702.1; -; mRNA.
DR CCDS; CCDS44566.1; -. [Q9UK99-2]
DR CCDS; CCDS7887.1; -. [Q9UK99-1]
DR RefSeq; NP_036307.2; NM_012175.3. [Q9UK99-1]
DR RefSeq; NP_208385.1; NM_033406.2. [Q9UK99-2]
DR PDB; 5HDW; X-ray; 2.00 A; A=278-407.
DR PDBsum; 5HDW; -.
DR AlphaFoldDB; Q9UK99; -.
DR SMR; Q9UK99; -.
DR BioGRID; 117657; 57.
DR DIP; DIP-53688N; -.
DR IntAct; Q9UK99; 17.
DR MINT; Q9UK99; -.
DR STRING; 9606.ENSP00000265651; -.
DR iPTMnet; Q9UK99; -.
DR PhosphoSitePlus; Q9UK99; -.
DR BioMuta; FBXO3; -.
DR DMDM; 145559474; -.
DR EPD; Q9UK99; -.
DR jPOST; Q9UK99; -.
DR MassIVE; Q9UK99; -.
DR MaxQB; Q9UK99; -.
DR PaxDb; Q9UK99; -.
DR PeptideAtlas; Q9UK99; -.
DR PRIDE; Q9UK99; -.
DR ProteomicsDB; 84745; -. [Q9UK99-1]
DR ProteomicsDB; 84746; -. [Q9UK99-2]
DR ProteomicsDB; 84747; -. [Q9UK99-3]
DR Antibodypedia; 25751; 140 antibodies from 23 providers.
DR DNASU; 26273; -.
DR Ensembl; ENST00000265651.8; ENSP00000265651.3; ENSG00000110429.14. [Q9UK99-1]
DR Ensembl; ENST00000448981.6; ENSP00000408836.2; ENSG00000110429.14. [Q9UK99-2]
DR Ensembl; ENST00000530401.5; ENSP00000433781.1; ENSG00000110429.14. [Q9UK99-3]
DR GeneID; 26273; -.
DR KEGG; hsa:26273; -.
DR MANE-Select; ENST00000265651.8; ENSP00000265651.3; NM_012175.4; NP_036307.2.
DR UCSC; uc001muz.4; human. [Q9UK99-1]
DR CTD; 26273; -.
DR DisGeNET; 26273; -.
DR GeneCards; FBXO3; -.
DR HGNC; HGNC:13582; FBXO3.
DR HPA; ENSG00000110429; Low tissue specificity.
DR MIM; 609089; gene.
DR neXtProt; NX_Q9UK99; -.
DR OpenTargets; ENSG00000110429; -.
DR PharmGKB; PA28040; -.
DR VEuPathDB; HostDB:ENSG00000110429; -.
DR eggNOG; KOG4408; Eukaryota.
DR GeneTree; ENSGT00940000153571; -.
DR InParanoid; Q9UK99; -.
DR OMA; YRDLVSC; -.
DR OrthoDB; 506060at2759; -.
DR PhylomeDB; Q9UK99; -.
DR TreeFam; TF329795; -.
DR PathwayCommons; Q9UK99; -.
DR SignaLink; Q9UK99; -.
DR BioGRID-ORCS; 26273; 20 hits in 1121 CRISPR screens.
DR ChiTaRS; FBXO3; human.
DR GenomeRNAi; 26273; -.
DR Pharos; Q9UK99; Tbio.
DR PRO; PR:Q9UK99; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UK99; protein.
DR Bgee; ENSG00000110429; Expressed in skeletal muscle tissue of rectus abdominis and 202 other tissues.
DR ExpressionAtlas; Q9UK99; baseline and differential.
DR Genevisible; Q9UK99; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR Gene3D; 2.60.40.1470; -; 1.
DR Gene3D; 3.40.1580.10; -; 1.
DR InterPro; IPR007474; ApaG_domain.
DR InterPro; IPR036767; ApaG_sf.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR028388; FBXO3.
DR InterPro; IPR018958; Knr4/Smi1-like_dom.
DR InterPro; IPR037883; Knr4/Smi1-like_sf.
DR PANTHER; PTHR46550:SF3; PTHR46550:SF3; 1.
DR Pfam; PF04379; DUF525; 1.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF09346; SMI1_KNR4; 1.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00860; SMI1_KNR4; 1.
DR SUPFAM; SSF110069; SSF110069; 1.
DR SUPFAM; SSF160631; SSF160631; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS51087; APAG; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Host-virus interaction; Nucleus;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..471
FT /note="F-box only protein 3"
FT /id="PRO_0000119877"
FT DOMAIN 10..56
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 278..408
FT /note="ApaG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00412"
FT REGION 419..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..448
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 36..40
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039614"
FT VAR_SEQ 414..415
FT /note="EM -> VS (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10531037,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_024395"
FT VAR_SEQ 416..471
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10531037,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_024396"
FT VARIANT 221
FT /note="V -> I (in dbSNP:rs1402954)"
FT /id="VAR_049037"
FT CONFLICT 28
FT /note="L -> M (in Ref. 2; CAB66560)"
FT /evidence="ECO:0000305"
FT CONFLICT 96..98
FT /note="IKK -> VKR (in Ref. 2; CAB66560)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> T (in Ref. 1; BAA91991)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="D -> G (in Ref. 2; CAB66560)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="F -> L (in Ref. 2; CAB66560)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="G -> E (in Ref. 2; CAB66560)"
FT /evidence="ECO:0000305"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 284..292
FT /evidence="ECO:0007829|PDB:5HDW"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:5HDW"
FT TURN 299..302
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 303..314
FT /evidence="ECO:0007829|PDB:5HDW"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 324..335
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 340..348
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 360..387
FT /evidence="ECO:0007829|PDB:5HDW"
FT STRAND 391..402
FT /evidence="ECO:0007829|PDB:5HDW"
SQ SEQUENCE 471 AA; 54561 MW; 5FDA81669264E0AD CRC64;
MAAMETETAP LTLESLPTDP LLLILSFLDY RDLINCCYVS RRLSQLSSHD PLWRRHCKKY
WLISEEEKTQ KNQCWKSLFI DTYSDVGRYI DHYAAIKKAW DDLKKYLEPR CPRMVLSLKE
GAREEDLDAV EAQIGCKLPD DYRCSYRIHN GQKLVVPGLL GSMALSNHYR SEDLLDVDTA
AGGFQQRQGL KYCLPLTFCI HTGLSQYIAV EAAEGRNKNE VFYQCPDQMA RNPAAIDMFI
IGATFTDWFT SYVKNVVSGG FPIIRDQIFR YVHDPECVAT TGDITVSVST SFLPELSSVH
PPHYFFTYRI RIEMSKDALP EKACQLDSRY WRITNAKGDV EEVQGPGVVG EFPIISPGRV
YEYTSCTTFS TTSGYMEGYY TFHFLYFKDK IFNVAIPRFH MACPTFRVSI ARLEMGPDEY
EEMEEEEEEE EEEDEDDDSA DMDESDEDDE EERRRRVFDV PIRRRRCSRL F
