FBX6_MOUSE
ID FBX6_MOUSE Reviewed; 295 AA.
AC Q9QZN4; A2A7H0; A2A7H2; B2KFL0; B2KFL2; Q3TML5; Q3UCB0;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=F-box only protein 6;
DE AltName: Full=F-box only protein 6b;
DE AltName: Full=F-box protein that recognizes sugar chains 2;
DE AltName: Full=F-box/G-domain protein 2;
GN Name=Fbxo6; Synonyms=Fbs2, Fbxo6b;
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 [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Kidney, and Lung;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
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 (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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, IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, SUGAR-BINDING,
RP AND TISSUE SPECIFICITY.
RX PubMed=12939278; DOI=10.1074/jbc.m304157200;
RA Yoshida Y., Tokunaga F., Chiba T., Iwai K., Tanaka K., Tai T.;
RT "Fbs2 is a new member of the E3 ubiquitin ligase family that recognizes
RT sugar chains.";
RL J. Biol. Chem. 278:43877-43884(2003).
RN [7]
RP FUNCTION, SUGAR-BINDING, 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276 AND THR-280, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
CC -!- FUNCTION: Substrate-recognition component of some SCF (SKP1-CUL1-F-box
CC protein)-type E3 ubiquitin ligase complexes. Involved in DNA damage
CC response by specifically recognizing activated CHEK1 (phosphorylated on
CC 'Ser-345'), promoting its ubiquitination and degradation.
CC Ubiquitination of CHEK1 is required to insure that activated CHEK1 does
CC not accumulate as cells progress through S phase, or when replication
CC forks encounter transient impediments during normal DNA replication (By
CC similarity). Involved in 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. Able to recognize and bind denatured
CC glycoproteins, which are modified with not only high-mannose but also
CC complex-type oligosaccharides. Also recognizes sulfated glycans.
CC {ECO:0000250, ECO:0000269|PubMed:12939278,
CC ECO:0000269|PubMed:15723043}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with CHEK1 and CUL1 (By similarity). Part of a SCF
CC (SKP1-cullin-F-box) protein ligase complex. Interacts with VCP.
CC {ECO:0000250, ECO:0000269|PubMed:12939278,
CC ECO:0000269|PubMed:15723043}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Present in liver and kidney (at protein level).
CC Widely expressed. {ECO:0000269|PubMed:12939278,
CC ECO:0000269|PubMed:18203720}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in embryos.
CC {ECO:0000269|PubMed:18203720}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM14908.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAQ51914.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAQ52206.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF176526; AAF09135.1; -; mRNA.
DR EMBL; AK002840; BAB22397.1; -; mRNA.
DR EMBL; AK150612; BAE29703.1; -; mRNA.
DR EMBL; AK152888; BAE31571.1; -; mRNA.
DR EMBL; AK165867; BAE38426.1; -; mRNA.
DR EMBL; AK170743; BAE41996.1; -; mRNA.
DR EMBL; AK171483; BAE42484.1; -; mRNA.
DR EMBL; AL606929; CAM14906.1; -; Genomic_DNA.
DR EMBL; AL606929; CAM14908.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CU207376; CAQ51912.1; -; Genomic_DNA.
DR EMBL; CU207417; CAQ51912.1; JOINED; Genomic_DNA.
DR EMBL; CU207376; CAQ51914.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CU207417; CAQ51914.1; JOINED; Genomic_DNA.
DR EMBL; CU207417; CAQ52204.1; -; Genomic_DNA.
DR EMBL; CU207376; CAQ52204.1; JOINED; Genomic_DNA.
DR EMBL; CU207417; CAQ52206.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CU207376; CAQ52206.1; JOINED; Genomic_DNA.
DR EMBL; CH466594; EDL14804.1; -; Genomic_DNA.
DR EMBL; CH466594; EDL14805.1; -; Genomic_DNA.
DR EMBL; CH466594; EDL14807.1; -; Genomic_DNA.
DR EMBL; BC017512; AAH17512.1; -; mRNA.
DR CCDS; CCDS18933.1; -.
DR RefSeq; NP_001157176.1; NM_001163704.1.
DR RefSeq; NP_001157177.1; NM_001163705.1.
DR RefSeq; NP_001157178.1; NM_001163706.1.
DR RefSeq; NP_001157179.1; NM_001163707.1.
DR RefSeq; NP_056612.1; NM_015797.4.
DR AlphaFoldDB; Q9QZN4; -.
DR SMR; Q9QZN4; -.
DR BioGRID; 206095; 11.
DR IntAct; Q9QZN4; 1.
DR STRING; 10090.ENSMUSP00000101331; -.
DR iPTMnet; Q9QZN4; -.
DR PhosphoSitePlus; Q9QZN4; -.
DR SwissPalm; Q9QZN4; -.
DR EPD; Q9QZN4; -.
DR jPOST; Q9QZN4; -.
DR MaxQB; Q9QZN4; -.
DR PaxDb; Q9QZN4; -.
DR PeptideAtlas; Q9QZN4; -.
DR PRIDE; Q9QZN4; -.
DR ProteomicsDB; 270967; -.
DR Antibodypedia; 28155; 239 antibodies from 28 providers.
DR DNASU; 50762; -.
DR Ensembl; ENSMUST00000030858; ENSMUSP00000030858; ENSMUSG00000055401.
DR Ensembl; ENSMUST00000056965; ENSMUSP00000062348; ENSMUSG00000055401.
DR Ensembl; ENSMUST00000105706; ENSMUSP00000101331; ENSMUSG00000055401.
DR Ensembl; ENSMUST00000168503; ENSMUSP00000130188; ENSMUSG00000055401.
DR GeneID; 50762; -.
DR KEGG; mmu:50762; -.
DR UCSC; uc008vud.2; mouse.
DR CTD; 26270; -.
DR MGI; MGI:1354743; Fbxo6.
DR VEuPathDB; HostDB:ENSMUSG00000055401; -.
DR eggNOG; ENOG502RZA6; Eukaryota.
DR GeneTree; ENSGT00940000159980; -.
DR InParanoid; Q9QZN4; -.
DR OMA; QDTQYWA; -.
DR OrthoDB; 922544at2759; -.
DR PhylomeDB; Q9QZN4; -.
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; 50762; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Fbxo2; mouse.
DR PRO; PR:Q9QZN4; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QZN4; protein.
DR Bgee; ENSMUSG00000055401; Expressed in urinary bladder and 57 other tissues.
DR ExpressionAtlas; Q9QZN4; baseline and differential.
DR Genevisible; Q9QZN4; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; IDA:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006516; P:glycoprotein catabolic process; IDA:MGI.
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; IMP:UniProtKB.
DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; IC:ParkinsonsUK-UCL.
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..295
FT /note="F-box only protein 6"
FT /id="PRO_0000119883"
FT DOMAIN 1..48
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT DOMAIN 69..250
FT /note="FBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00482"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRD1"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 280
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 77
FT /note="R -> K (in Ref. 3; CAQ52204/CAQ52206/CAQ51912/
FT CAQ51914 and 4; EDL14807/EDL14805/EDL14804)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="T -> A (in Ref. 2; BAE29703)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 34493 MW; D515D3C25CC73B22 CRC64;
MVHINELPEN ILLELFIHIP APQLLRNCRL VCRLWRDLID VVSLWKRKSL REGFFTKDRC
EPVEDWKVFY ILCSLQRNLL RNPCAEENLS SWRIDSNGGD RWKVETLPGS CGTSFPDNKV
KKYFVTSFEM CLKSQMVDLK AEGYCEELMD TFRPDIVVKD WVAPRADCGC TYQLRVQLAS
ADYIVLASFE PPPVTFQQWN DAKWQEISHT FSDYPPGVRH ILFQHGGQDT QFWKGWYGPR
VTNSSIIISH RTAKNPPPAR TLPEETVVIG RRRRASDSNT HEGFFWQGLW QRLRR
