FBX6_HUMAN
ID FBX6_HUMAN Reviewed; 293 AA.
AC Q9NRD1; B1AK42; B2RC88; Q9UKT3;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=F-box only protein 6;
DE AltName: Full=F-box protein that recognizes sugar chains 2;
DE AltName: Full=F-box/G-domain protein 2;
GN Name=FBXO6; Synonyms=FBG2, FBS2, FBX6;
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 [MRNA].
RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2;
RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M.,
RA Pagano M.;
RT "Identification of a family of human F-box proteins.";
RL Curr. Biol. 9:1177-1179(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10945468; DOI=10.1006/geno.2000.6211;
RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.;
RT "cDNA cloning and expression analysis of new members of the mammalian F-box
RT protein family.";
RL Genomics 67:40-47(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [7]
RP FUNCTION, SUGAR-BINDING, INTERACTION WITH CUL1, AND MUTAGENESIS OF
RP 241-TYR-TRP-242.
RX PubMed=18203720; DOI=10.1074/jbc.m709508200;
RA Glenn K.A., Nelson R.F., Wen H.M., Mallinger A.J., Paulson H.L.;
RT "Diversity in tissue expression, substrate binding, and SCF complex
RT formation for a lectin family of ubiquitin ligases.";
RL J. Biol. Chem. 283:12717-12729(2008).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A SCF PROTEIN LIGASE
RP COMPLEX, AND INTERACTION WITH CHEK1.
RX PubMed=19716789; DOI=10.1016/j.molcel.2009.06.030;
RA Zhang Y.-W., Brognard J., Coughlin C., You Z., Dolled-Filhart M.,
RA Aslanian A., Manning G., Abraham R.T., Hunter T.;
RT "The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity
RT to replication stress.";
RL Mol. Cell 35:442-453(2009).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258 AND SER-284, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Substrate-recognition component of some SCF (SKP1-CUL1-F-box
CC protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic
CC reticulum-associated degradation pathway (ERAD) for misfolded lumenal
CC proteins by recognizing and binding sugar chains on unfolded
CC glycoproteins that are retrotranslocated into the cytosol and promoting
CC their ubiquitination and subsequent degradation. Able to recognize and
CC bind denatured glycoproteins, which are modified with not only high-
CC mannose but also complex-type oligosaccharides. Also recognizes
CC sulfated glycans. Also involved in DNA damage response by specifically
CC recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting
CC its ubiquitination and degradation. Ubiquitination of CHEK1 is required
CC to insure that activated CHEK1 does not accumulate as cells progress
CC through S phase, or when replication forks encounter transient
CC impediments during normal DNA replication.
CC {ECO:0000269|PubMed:18203720, ECO:0000269|PubMed:19716789}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with VCP (By similarity). Part of a SCF (SKP1-
CC cullin-F-box) protein ligase complex. Interacts with CHEK1 and CUL1.
CC {ECO:0000250, ECO:0000269|PubMed:18203720,
CC ECO:0000269|PubMed:19716789}.
CC -!- INTERACTION:
CC Q9NRD1; Q13616: CUL1; NbExp=3; IntAct=EBI-3938499, EBI-359390;
CC Q9NRD1; Q08380: LGALS3BP; NbExp=2; IntAct=EBI-3938499, EBI-354956;
CC Q9NRD1; P63208: SKP1; NbExp=8; IntAct=EBI-3938499, EBI-307486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19716789}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF04470.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=hFBG2;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_other_821";
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DR EMBL; AF129536; AAF04470.1; ALT_INIT; mRNA.
DR EMBL; AF233223; AAF67153.1; -; mRNA.
DR EMBL; AK314989; BAG37485.1; -; mRNA.
DR EMBL; AL031731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71696.1; -; Genomic_DNA.
DR EMBL; BC020880; AAH20880.1; -; mRNA.
DR CCDS; CCDS133.1; -.
DR RefSeq; NP_060908.1; NM_018438.5.
DR RefSeq; XP_005263505.1; XM_005263448.4.
DR RefSeq; XP_005263506.1; XM_005263449.4.
DR RefSeq; XP_005263508.1; XM_005263451.4.
DR RefSeq; XP_006710634.1; XM_006710571.3.
DR RefSeq; XP_011539534.1; XM_011541232.2.
DR RefSeq; XP_016856496.1; XM_017001007.1.
DR AlphaFoldDB; Q9NRD1; -.
DR SMR; Q9NRD1; -.
DR BioGRID; 117654; 727.
DR CORUM; Q9NRD1; -.
DR IntAct; Q9NRD1; 51.
DR MINT; Q9NRD1; -.
DR STRING; 9606.ENSP00000365944; -.
DR iPTMnet; Q9NRD1; -.
DR PhosphoSitePlus; Q9NRD1; -.
DR BioMuta; FBXO6; -.
DR DMDM; 24636846; -.
DR EPD; Q9NRD1; -.
DR jPOST; Q9NRD1; -.
DR MassIVE; Q9NRD1; -.
DR MaxQB; Q9NRD1; -.
DR PaxDb; Q9NRD1; -.
DR PeptideAtlas; Q9NRD1; -.
DR PRIDE; Q9NRD1; -.
DR ProteomicsDB; 82338; -.
DR Antibodypedia; 28155; 239 antibodies from 28 providers.
DR DNASU; 26270; -.
DR Ensembl; ENST00000376753.9; ENSP00000365944.4; ENSG00000116663.11.
DR GeneID; 26270; -.
DR KEGG; hsa:26270; -.
DR MANE-Select; ENST00000376753.9; ENSP00000365944.4; NM_018438.6; NP_060908.1.
DR UCSC; uc001aso.4; human.
DR CTD; 26270; -.
DR DisGeNET; 26270; -.
DR GeneCards; FBXO6; -.
DR HGNC; HGNC:13585; FBXO6.
DR HPA; ENSG00000116663; Low tissue specificity.
DR MIM; 605647; gene.
DR neXtProt; NX_Q9NRD1; -.
DR OpenTargets; ENSG00000116663; -.
DR PharmGKB; PA28046; -.
DR VEuPathDB; HostDB:ENSG00000116663; -.
DR eggNOG; ENOG502RZA6; Eukaryota.
DR GeneTree; ENSGT00940000159980; -.
DR HOGENOM; CLU_068548_0_0_1; -.
DR InParanoid; Q9NRD1; -.
DR OMA; QDTQYWA; -.
DR OrthoDB; 922544at2759; -.
DR PhylomeDB; Q9NRD1; -.
DR TreeFam; TF320527; -.
DR PathwayCommons; Q9NRD1; -.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9NRD1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 26270; 9 hits in 1128 CRISPR screens.
DR ChiTaRS; FBXO6; human.
DR GeneWiki; FBXO6; -.
DR GenomeRNAi; 26270; -.
DR Pharos; Q9NRD1; Tbio.
DR PRO; PR:Q9NRD1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NRD1; protein.
DR Bgee; ENSG00000116663; Expressed in granulocyte and 139 other tissues.
DR ExpressionAtlas; Q9NRD1; baseline and differential.
DR Genevisible; Q9NRD1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IBA:GO_Central.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IEA:Ensembl.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; TAS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:UniProtKB.
DR GO; GO:0006516; P:glycoprotein catabolic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
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; PF12937; F-box-like; 1.
DR Pfam; PF04300; FBA; 1.
DR SMART; SM01198; FBA; 1.
DR SMART; SM00256; FBOX; 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 Cytoplasm; DNA damage; DNA repair; Phosphoprotein; Reference proteome;
KW Ubl conjugation pathway; Unfolded protein response.
FT CHAIN 1..293
FT /note="F-box only protein 6"
FT /id="PRO_0000119882"
FT DOMAIN 10..57
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 78..259
FT /note="FBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00482"
FT REGION 261..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..278
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 60
FT /note="R -> Q (in dbSNP:rs3125818)"
FT /id="VAR_049039"
FT VARIANT 201
FT /note="P -> T (in dbSNP:rs2294639)"
FT /id="VAR_022158"
FT MUTAGEN 241..242
FT /note="YW->AA: Abolishes interaction with glycosylated
FT concanavalin-A in vitro."
FT /evidence="ECO:0000269|PubMed:18203720"
FT CONFLICT 18
FT /note="E -> D (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="M -> L (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="E -> K (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="E -> N (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="E -> D (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="D -> E (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="Y -> S (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="M -> L (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 143..144
FT /note="SQ -> WE (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 149..152
FT /note="VAEG -> LADR (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="R -> G (in Ref. 1; AAF04470)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 293 AA; 33933 MW; EA4235CD9CCD80FF CRC64;
MDAPHSKAAL DSINELPENI LLELFTHVPA RQLLLNCRLV CSLWRDLIDL MTLWKRKCLR
EGFITKDWDQ PVADWKIFYF LRSLHRNLLR NPCAEEDMFA WQIDFNGGDR WKVESLPGAH
GTDFPDPKVK KYFVTSYEMC LKSQLVDLVA EGYWEELLDT FRPDIVVKDW FAARADCGCT
YQLKVQLASA DYFVLASFEP PPVTIQQWNN ATWTEVSYTF SDYPRGVRYI LFQHGGRDTQ
YWAGWYGPRV TNSSIVVSPK MTRNQASSEA QPGQKHGQEE AAQSPYRAVV QIF
