FCOR_MOUSE
ID FCOR_MOUSE Reviewed; 106 AA.
AC P0DJI6; A5S7P8;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Foxo1-corepressor;
DE Short=FCoR;
DE EC=2.3.1.-;
DE AltName: Full=Foxo1 CoRepressor;
GN Name=Fcor;
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], FUNCTION IN ACETYLATION AND TRANSCRIPTIONAL
RP REPRESSION OF FOXO1, INTERACTION WITH FOXO1 AND FOXO3, PHOSPHORYLATION AT
RP THR-93, PHOSPHORYLATION BY PKA, ASSOCIATION WITH CHROMATIN, SUBCELLULAR
RP LOCATION, INDUCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ILE-78; THR-80; LEU-81; LEU-85; LEU-87; SER-92 AND THR-93.
RC TISSUE=Adipocyte;
RX PubMed=22510882; DOI=10.1038/emboj.2012.97;
RA Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T.,
RA Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.;
RT "Novel repressor regulates insulin sensitivity through interaction with
RT Foxo1.";
RL EMBO J. 31:2275-2295(2012).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-106.
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
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).
CC -!- FUNCTION: Regulator of adipocytes that acts by repressing FOXO1
CC transcriptional activity. Acts by promoting acetylation of FOXO1, both
CC by preventing the interaction between FOXO1 and SIRT1 deacetylase, and
CC by mediating acetyltransferase activity in vitro. Regulates insulin
CC sensitivity and energy metabolism. {ECO:0000269|PubMed:22510882}.
CC -!- SUBUNIT: Interacts with FOXO1 (via N-terminal domain); the interaction
CC is direct, occurs in a forskolin-independent manner that prevents SIRT1
CC binding to FOXO1. Interacts with FOXO3. Does not interact with FOXO4.
CC {ECO:0000269|PubMed:22510882}.
CC -!- INTERACTION:
CC P0DJI6; Q9R1E0: Foxo1; NbExp=12; IntAct=EBI-6126630, EBI-1371343;
CC P0DJI6; Q9WVH4: Foxo3; NbExp=2; IntAct=EBI-6126630, EBI-6127038;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22510882}.
CC Nucleus {ECO:0000269|PubMed:22510882}. Note=Imported into the nucleus
CC following phosphorylation at Thr-93 upon treatment of cells with
CC forskolin. Probably shuttles between the nucleus and the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in adipocytes. Expressed in brown and
CC white adipose tissue but not in liver. Protein levels in brown and
CC white adipose tissues decrease following fasting (at protein level).
CC Expressed in white and brown adipose tissues. Expressed in adipocytes.
CC Not expressed in liver, skeletal muscle and brain.
CC {ECO:0000269|PubMed:22510882}.
CC -!- INDUCTION: Up-regulated during adipocyte differentiation. Up-regulated
CC by starved state in white (WAT) and brown (BAT) adipose tissues. Down-
CC regulated during fasting in WAT and BAT. Up-regulated during cold
CC exposure in BAT. {ECO:0000269|PubMed:22510882}.
CC -!- PTM: Phosphorylated at Thr-93 by PKA, leading to import into the
CC nucleus. {ECO:0000269|PubMed:22510882}.
CC -!- DISRUPTION PHENOTYPE: Mice are glucose intolerant and insulin
CC resistant, despite being leaner than wild-type mice.
CC {ECO:0000269|PubMed:22510882}.
CC -!- CAUTION: It is unclear whether the protein is conserved in human: no
CC ortholog has been identified yet although antibodies against Fcor stain
CC human tissues. {ECO:0000305}.
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; AC087183; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466566; EDL21945.1; -; Genomic_DNA.
DR EMBL; BY341563; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK019104; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK019114; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; P0DJI6; -.
DR IntAct; P0DJI6; 2.
DR iPTMnet; P0DJI6; -.
DR PhosphoSitePlus; P0DJI6; -.
DR PRIDE; P0DJI6; -.
DR Ensembl; ENSMUST00000159364; ENSMUSP00000146366; ENSMUSG00000089665.
DR MGI; MGI:1915484; Fcor.
DR VEuPathDB; HostDB:ENSMUSG00000089665; -.
DR GeneTree; ENSGT00960000193309; -.
DR PRO; PR:P0DJI6; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P0DJI6; protein.
DR Bgee; ENSMUSG00000089665; Expressed in epididymal fat pad and 208 other tissues.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016407; F:acetyltransferase activity; TAS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0070417; P:cellular response to cold; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006473; P:protein acetylation; IDA:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..106
FT /note="Foxo1-corepressor"
FT /id="PRO_0000418015"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 78..87
FT /note="Nuclear export signal"
FT /evidence="ECO:0000305"
FT MOD_RES 93
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 78
FT /note="I->A: Abolishes inhibition of FOXO1 transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 80
FT /note="T->A: Abolishes inhibition of FOXO1 transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 81
FT /note="L->A: Enhances FOXO1 nuclear translocation but does
FT not abolish inhibition of FOXO1 transcriptional activity in
FT the absence of forskolin."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 85
FT /note="L->A: Abolishes inhibition of FOXO1 transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 87
FT /note="L->A: Abolishes inhibition of FOXO1 transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 92
FT /note="S->A: Does not inhibits subcellular localization.
FT Does not affect phosphorylation in response to forskolin."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 93
FT /note="T->A: Abolishes phosphorylation in response to
FT forskolin. Localizes mainly to the cytosol. Weakly enhances
FT FOXO1 acetylation. Weakly abolishes inhibition of FOXO1
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:22510882"
FT MUTAGEN 93
FT /note="T->D: Mimicks phosphorylation state, localizes
FT mainly to the nucleus. Strongly enhances FOXO1 acetylation.
FT Strongly abolishes inhibition of FOXO1 transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:22510882"
SQ SEQUENCE 106 AA; 11233 MW; 4A4F7D521A3D4197 CRC64;
MGGPTRRHQE EGSAECLGGP STRAAPGPGL RDFHFTTAGP SKADRLGDAA QIHRERMRPV
QCGDGSGERV FLQSPGSIGT LYIRLDLNSQ RSTCCCLLNA GTKGMC
