PPR3C_MOUSE
ID PPR3C_MOUSE Reviewed; 317 AA.
AC Q7TMB3; O08541; Q8BJW8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 3C;
DE AltName: Full=Protein phosphatase 1 regulatory subunit 5;
DE Short=PP1 subunit R5;
DE AltName: Full=Protein targeting to glycogen;
DE Short=PTG;
GN Name=Ppp1r3c {ECO:0000312|MGI:MGI:1858229};
GN Synonyms=Ppp1r5 {ECO:0000250|UniProtKB:Q9UQK1};
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] {ECO:0000312|EMBL:AAH52769.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH52769.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH54739.1}, and
RC Olfactory epithelium {ECO:0000312|EMBL:AAH52769.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAB49689.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-317, FUNCTION, ASSOCIATION WITH GLYCOGEN,
RP AND INTERACTION WITH PPP1CC.
RX PubMed=9045612; DOI=10.1126/science.275.5305.1475;
RA Printen J.A., Brady M.J., Saltiel A.R.;
RT "PTG, a protein phosphatase 1-binding protein with a role in glycogen
RT metabolism.";
RL Science 275:1475-1478(1997).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAC37313.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 126-317.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC37313.1};
RC TISSUE=Muellerian duct {ECO:0000312|EMBL:BAC37313.1};
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 [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=9242697; DOI=10.1074/jbc.272.32.20198;
RA Brady M.J., Printen J.A., Mastick C.C., Saltiel A.R.;
RT "Role of protein targeting to glycogen (PTG) in the regulation of protein
RT phosphatase-1 activity.";
RL J. Biol. Chem. 272:20198-20204(1997).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=9756875; DOI=10.1074/jbc.273.41.26421;
RA Berman H.K., O'Doherty R.M., Anderson P., Newgard C.B.;
RT "Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes
RT causes profound activation of glycogen synthesis independent of normal
RT hormone- and substrate-mediated regulatory mechanisms.";
RL J. Biol. Chem. 273:26421-26425(1998).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=10862764; DOI=10.1074/jbc.m002427200;
RA Gasa R., Jensen P.B., Berman H.K., Brady M.J., DePaoli-Roach A.A.,
RA Newgard C.B.;
RT "Distinctive regulatory and metabolic properties of glycogen-targeting
RT subunits of protein phosphatase-1 (PTG, GL, GM/RGl) expressed in
RT hepatocytes.";
RL J. Biol. Chem. 275:26396-26403(2000).
RN [7] {ECO:0000305}
RP MUTAGENESIS OF VAL-85; PHE-87; ASP-247 AND GLU-250.
RX PubMed=10938087; DOI=10.1074/jbc.m005541200;
RA Fong N.M., Jensen T.C., Shah A.S., Parekh N.N., Saltiel A.R., Brady M.J.;
RT "Identification of binding sites on protein targeting to glycogen for
RT enzymes of glycogen metabolism.";
RL J. Biol. Chem. 275:35034-35039(2000).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=10998419; DOI=10.1074/jbc.m006251200;
RA Lerin C., Montell E., Berman H.K., Newgard C.B., Gomez-Foix A.M.;
RT "Overexpression of protein targeting to glycogen in cultured human muscle
RT cells stimulates glycogen synthesis independent of glycogen and glucose 6-
RT phosphate levels.";
RL J. Biol. Chem. 275:39991-39995(2000).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=10683377; DOI=10.1172/jci8673;
RA O'Doherty R.M., Jensen P.B., Anderson P., Jones J.G., Berman H.K.,
RA Kearney D., Newgard C.B.;
RT "Activation of direct and indirect pathways of glycogen synthesis by
RT hepatic overexpression of protein targeting to glycogen.";
RL J. Clin. Invest. 105:479-488(2000).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=12805359; DOI=10.1074/jbc.m303846200;
RA Greenberg C.C., Meredith K.N., Yan L., Brady M.J.;
RT "Protein targeting to glycogen overexpression results in the specific
RT enhancement of glycogen storage in 3T3-L1 adipocytes.";
RL J. Biol. Chem. 278:30835-30842(2003).
RN [11] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12727934; DOI=10.1172/jci200317975;
RA Crosson S.M., Khan A., Printen J., Pessin J.E., Saltiel A.R.;
RT "PTG gene deletion causes impaired glycogen synthesis and developmental
RT insulin resistance.";
RL J. Clin. Invest. 111:1423-1432(2003).
RN [12] {ECO:0000305}
RP FUNCTION.
RX PubMed=15322104; DOI=10.1074/jbc.m405660200;
RA Green A.R., Aiston S., Greenberg C.C., Freeman S., Poucher S.M.,
RA Brady M.J., Agius L.;
RT "The glycogenic action of protein targeting to glycogen in hepatocytes
RT involves multiple mechanisms including phosphorylase inactivation and
RT glycogen synthase translocation.";
RL J. Biol. Chem. 279:46474-46482(2004).
RN [13] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16354703; DOI=10.1128/mcb.26.1.334-342.2006;
RA Greenberg C.C., Danos A.M., Brady M.J.;
RT "Central role for protein targeting to glycogen in the maintenance of
RT cellular glycogen stores in 3T3-L1 adipocytes.";
RL Mol. Cell. Biol. 26:334-342(2006).
CC -!- FUNCTION: Acts as a glycogen-targeting subunit for PP1 and regulates
CC its activity. Activates glycogen synthase, reduces glycogen
CC phosphorylase activity and limits glycogen breakdown. Dramatically
CC increases basal and insulin-stimulated glycogen synthesis upon
CC overexpression in a variety of cell types.
CC {ECO:0000269|PubMed:10683377, ECO:0000269|PubMed:10862764,
CC ECO:0000269|PubMed:10998419, ECO:0000269|PubMed:12727934,
CC ECO:0000269|PubMed:12805359, ECO:0000269|PubMed:15322104,
CC ECO:0000269|PubMed:16354703, ECO:0000269|PubMed:9045612,
CC ECO:0000269|PubMed:9242697, ECO:0000269|PubMed:9756875}.
CC -!- SUBUNIT: Interacts with PPP1CC catalytic subunit of PP1 and associates
CC with glycogen. Forms complexes with glycogen phosphorylase, glycogen
CC synthase and phosphorylase kinase which is necessary for its regulation
CC of PP1 activity. Also interacts with EPM2A/laforin.
CC {ECO:0000250|UniProtKB:Q9UQK1, ECO:0000269|PubMed:9045612}.
CC -!- DOMAIN: The N-terminal region is required for binding to PP1, the
CC central region is required for binding to glycogen and the C-terminal
CC region is required for binding to glycogen phosphorylase, glycogen
CC synthase and phosphorylase kinase. {ECO:0000269|PubMed:10938087}.
CC -!- PTM: Ubiquitinated by NHLRC1/malin in a EPM2A/laforin-dependent manner.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice display embryonic lethality when homozygous.
CC Heterozygotes display decreased protein levels, decreased glycogen
CC accumulation and glycogen synthase activity, reduced insulin-stimulated
CC glycogen synthesis and progressive age-dependent glucose intolerance.
CC When Ppp1r3c is silenced in adults, they display decreased PP1 activity
CC and glycogen accumulation, increased phosphorylation of glycogen
CC phosphorylase, increased GLUT1 levels, increased glucose uptake and
CC increased glycogen degradation. {ECO:0000269|PubMed:12727934,
CC ECO:0000269|PubMed:16354703}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB49689.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC052769; AAH52769.1; -; mRNA.
DR EMBL; BC054739; AAH54739.1; -; mRNA.
DR EMBL; U89924; AAB49689.1; ALT_INIT; mRNA.
DR EMBL; AK078506; BAC37313.1; -; mRNA.
DR CCDS; CCDS37968.1; -.
DR RefSeq; NP_058550.1; NM_016854.2.
DR AlphaFoldDB; Q7TMB3; -.
DR SMR; Q7TMB3; -.
DR BioGRID; 207306; 1.
DR STRING; 10090.ENSMUSP00000084578; -.
DR CAZy; CBM21; Carbohydrate-Binding Module Family 21.
DR iPTMnet; Q7TMB3; -.
DR PhosphoSitePlus; Q7TMB3; -.
DR MaxQB; Q7TMB3; -.
DR PaxDb; Q7TMB3; -.
DR PRIDE; Q7TMB3; -.
DR ProteomicsDB; 291841; -.
DR Antibodypedia; 16368; 113 antibodies from 24 providers.
DR DNASU; 53412; -.
DR Ensembl; ENSMUST00000087321; ENSMUSP00000084578; ENSMUSG00000067279.
DR GeneID; 53412; -.
DR KEGG; mmu:53412; -.
DR UCSC; uc008hhs.1; mouse.
DR CTD; 5507; -.
DR MGI; MGI:1858229; Ppp1r3c.
DR VEuPathDB; HostDB:ENSMUSG00000067279; -.
DR eggNOG; KOG3986; Eukaryota.
DR GeneTree; ENSGT00940000155648; -.
DR HOGENOM; CLU_040215_2_1_1; -.
DR InParanoid; Q7TMB3; -.
DR OMA; CISYQSG; -.
DR OrthoDB; 1232750at2759; -.
DR PhylomeDB; Q7TMB3; -.
DR TreeFam; TF105537; -.
DR Reactome; R-MMU-3322077; Glycogen synthesis.
DR BioGRID-ORCS; 53412; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Ppp1r3c; mouse.
DR PRO; PR:Q7TMB3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q7TMB3; protein.
DR Bgee; ENSMUSG00000067279; Expressed in sternocleidomastoid and 239 other tissues.
DR Genevisible; Q7TMB3; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0042587; C:glycogen granule; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IBA:GO_Central.
DR GO; GO:0050196; F:[phosphorylase] phosphatase activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:2001069; F:glycogen binding; IEP:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:MGI.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:MGI.
DR GO; GO:0005978; P:glycogen biosynthetic process; IDA:MGI.
DR GO; GO:0005977; P:glycogen metabolic process; IDA:MGI.
DR GO; GO:0006605; P:protein targeting; TAS:MGI.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:0005981; P:regulation of glycogen catabolic process; ISO:MGI.
DR Gene3D; 2.60.40.2440; -; 1.
DR InterPro; IPR005036; CBM21_dom.
DR InterPro; IPR038175; CBM21_dom_sf.
DR InterPro; IPR017434; Pase-1_reg-su_3B/C/D_met.
DR InterPro; IPR030683; PP1_3C.
DR PANTHER; PTHR12307:SF15; PTHR12307:SF15; 1.
DR Pfam; PF03370; CBM_21; 1.
DR PIRSF; PIRSF038207; PP1_GT_animal; 1.
DR PIRSF; PIRSF500813; PP1_PTG; 1.
DR PROSITE; PS51159; CBM21; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Glycogen metabolism; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..317
FT /note="Protein phosphatase 1 regulatory subunit 3C"
FT /id="PRO_0000285928"
FT DOMAIN 149..257
FT /note="CBM21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00491"
FT REGION 141..263
FT /note="Interaction with EPM2A"
FT /evidence="ECO:0000250|UniProtKB:Q9UQK1"
FT MOTIF 84..87
FT /note="PP1-binding motif"
FT MUTAGEN 85
FT /note="V->A: Abolishes binding to PP1 but has no effect on
FT binding to glycogen synthase, glycogen phosphorylase or
FT glycogen; when associated with A-87."
FT /evidence="ECO:0000269|PubMed:10938087"
FT MUTAGEN 87
FT /note="F->A: Abolishes binding to PP1 but has no effect on
FT binding to glycogen synthase, glycogen phosphorylase or
FT glycogen; when associated with A-85."
FT /evidence="ECO:0000269|PubMed:10938087"
FT MUTAGEN 247
FT /note="D->A: Abolishes binding to glycogen synthase and
FT glycogen phosphorylase but has no effect on binding to PP1
FT or glycogen; when associated with A-250."
FT /evidence="ECO:0000269|PubMed:10938087"
FT MUTAGEN 250
FT /note="E->A: Abolishes binding to glycogen synthase and
FT glycogen phosphorylase but has no effect on binding to PP1
FT or glycogen; when associated with A-247."
FT /evidence="ECO:0000269|PubMed:10938087"
FT CONFLICT 165
FT /note="Q -> E (in Ref. 2; AAB49689)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 36460 MW; 8DC8941B733649D6 CRC64;
MSCTRMIHVL DPRPLTSSVM PVDMAMRICL AHSPPLKSFL GPYNGFQRRN FVNKLKPLKP
CLSVKQEAKS QSEWKSPHNQ AKKRVVFADS KGLSLTAIHV FSDLPEEPAW DLQFDLLDLN
DISSSLKLHE EKNLVFDFPQ PSTDYLSFRD RFQKNFVCLE NCSLQDRTVT GTVKVKNVSF
EKKVQVRITF DTWKTYTDVD CVYMKNVYSS SDSDTFSFAI DLPRVIPTEE KIEFCISYHA
NGRIFWDNNE GQNYRIVHVQ WKPDGVQTQV APKDCAFQQG PPKTEIEPTV FGSPRLASGL
FPEWQSWGRV ENLTSYR
