PPR3C_HUMAN
ID PPR3C_HUMAN Reviewed; 317 AA.
AC Q9UQK1; B2R7X0; O95686;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 144.
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|HGNC:HGNC:9293};
GN Synonyms=PPP1R5 {ECO:0000312|EMBL:CAA77082.1};
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] {ECO:0000305, ECO:0000312|EMBL:CAA77082.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH PPP1CC.
RC TISSUE=Gall bladder {ECO:0000269|PubMed:8985175};
RX PubMed=8985175; DOI=10.1016/s0014-5793(96)01357-9;
RA Doherty M.J., Young P.R., Cohen P.T.W.;
RT "Amino acid sequence of a novel protein phosphatase 1 binding protein (R5)
RT which is related to the liver- and muscle-specific glycogen binding
RT subunits of protein phosphatase 1.";
RL FEBS Lett. 399:339-343(1996).
RN [2] {ECO:0000312|EMBL:AAD33215.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10222257; DOI=10.1006/bbrc.1999.0614;
RA Permana P.A., Luczy-Bachman G., Bogardus C.;
RT "Protein targeting to glycogen/PPP1R5: screening of coding and flanking
RT genomic regions for polymorphisms and association analysis with insulin
RT action in Pima Indians.";
RL Biochem. Biophys. Res. Commun. 258:184-186(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 MRNA].
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5] {ECO:0000312|EMBL:AL359986}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6] {ECO:0000312|EMBL:CAD97641.1}
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 [7] {ECO:0000312|EMBL:AAH12625.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle {ECO:0000312|EMBL:AAH12625.1};
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 [8] {ECO:0000305}
RP INTERACTION WITH EPM2A, AND MUTAGENESIS OF VAL-85; PHE-87; ASP-247 AND
RP ASP-250.
RX PubMed=14532330; DOI=10.1093/hmg/ddg340;
RA Fernandez-Sanchez M.E., Criado-Garcia O., Heath K.E., Garcia-Fojeda B.,
RA Medrano-Fernandez I., Gomez-Garre P., Sanz P., Serratosa J.M.,
RA Rodriguez de Cordoba S.;
RT "Laforin, the dual-phosphatase responsible for Lafora disease, interacts
RT with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances
RT glycogen accumulation.";
RL Hum. Mol. Genet. 12:3161-3171(2003).
RN [9]
RP UBIQUITINATION, AND INTERACTION WITH EPM2A.
RX PubMed=18070875; DOI=10.1074/jbc.m708712200;
RA Worby C.A., Gentry M.S., Dixon J.E.;
RT "Malin decreases glycogen accumulation by promoting the degradation of
RT protein targeting to glycogen (PTG).";
RL J. Biol. Chem. 283:4069-4076(2008).
RN [10]
RP VARIANT SER-249.
RX PubMed=21738631; DOI=10.1371/journal.pone.0021294;
RA Guerrero R., Vernia S., Sanz R., Abreu-Rodriguez I., Almaraz C.,
RA Garcia-Hoyos M., Michelucci R., Tassinari C.A., Riguzzi P., Nobile C.,
RA Sanz P., Serratosa J.M., Gomez-Garre P.;
RT "A PTG variant contributes to a milder phenotype in Lafora disease.";
RL PLoS ONE 6:E21294-E21294(2011).
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:0000250|UniProtKB:Q7TMB3, ECO:0000269|PubMed:8985175}.
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:Q7TMB3, ECO:0000269|PubMed:14532330,
CC ECO:0000269|PubMed:18070875, ECO:0000269|PubMed:8985175}.
CC -!- INTERACTION:
CC Q9UQK1; O95278: EPM2A; NbExp=5; IntAct=EBI-2506727, EBI-2506661;
CC Q9UQK1; P13807: GYS1; NbExp=2; IntAct=EBI-2506727, EBI-740553;
CC Q9UQK1; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-2506727, EBI-2341787;
CC Q9UQK1; Q9BS40: LXN; NbExp=3; IntAct=EBI-2506727, EBI-1044504;
CC Q9UQK1; P62136: PPP1CA; NbExp=5; IntAct=EBI-2506727, EBI-357253;
CC Q9UQK1; P62140: PPP1CB; NbExp=9; IntAct=EBI-2506727, EBI-352350;
CC Q9UQK1; P36873: PPP1CC; NbExp=4; IntAct=EBI-2506727, EBI-356283;
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:0000250|UniProtKB:Q7TMB3}.
CC -!- PTM: Ubiquitinated by NHLRC1/malin in a EPM2A/laforin-dependent manner.
CC {ECO:0000269|PubMed:18070875}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD33215.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; Y18207; CAA77082.1; -; mRNA.
DR EMBL; AF110824; AAD33215.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK313149; BAG35967.1; -; mRNA.
DR EMBL; BX537399; CAD97641.1; -; mRNA.
DR EMBL; AL359986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50107.1; -; Genomic_DNA.
DR EMBL; BC012625; AAH12625.1; -; mRNA.
DR CCDS; CCDS7416.1; -.
DR RefSeq; NP_005389.1; NM_005398.6.
DR AlphaFoldDB; Q9UQK1; -.
DR SMR; Q9UQK1; -.
DR BioGRID; 111500; 40.
DR IntAct; Q9UQK1; 26.
DR MINT; Q9UQK1; -.
DR STRING; 9606.ENSP00000238994; -.
DR CAZy; CBM21; Carbohydrate-Binding Module Family 21.
DR iPTMnet; Q9UQK1; -.
DR PhosphoSitePlus; Q9UQK1; -.
DR BioMuta; PPP1R3C; -.
DR DMDM; 146325084; -.
DR MassIVE; Q9UQK1; -.
DR PaxDb; Q9UQK1; -.
DR PeptideAtlas; Q9UQK1; -.
DR PRIDE; Q9UQK1; -.
DR ProteomicsDB; 85553; -.
DR Antibodypedia; 16368; 113 antibodies from 24 providers.
DR DNASU; 5507; -.
DR Ensembl; ENST00000238994.6; ENSP00000238994.5; ENSG00000119938.9.
DR GeneID; 5507; -.
DR KEGG; hsa:5507; -.
DR MANE-Select; ENST00000238994.6; ENSP00000238994.5; NM_005398.7; NP_005389.1.
DR UCSC; uc001kho.4; human.
DR CTD; 5507; -.
DR DisGeNET; 5507; -.
DR GeneCards; PPP1R3C; -.
DR HGNC; HGNC:9293; PPP1R3C.
DR HPA; ENSG00000119938; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 602999; gene.
DR neXtProt; NX_Q9UQK1; -.
DR OpenTargets; ENSG00000119938; -.
DR PharmGKB; PA33653; -.
DR VEuPathDB; HostDB:ENSG00000119938; -.
DR eggNOG; KOG3986; Eukaryota.
DR GeneTree; ENSGT00940000155648; -.
DR HOGENOM; CLU_040215_2_1_1; -.
DR InParanoid; Q9UQK1; -.
DR OMA; CISYQSG; -.
DR OrthoDB; 1232750at2759; -.
DR PhylomeDB; Q9UQK1; -.
DR TreeFam; TF105537; -.
DR PathwayCommons; Q9UQK1; -.
DR Reactome; R-HSA-3322077; Glycogen synthesis.
DR Reactome; R-HSA-3785653; Myoclonic epilepsy of Lafora.
DR SignaLink; Q9UQK1; -.
DR BioGRID-ORCS; 5507; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; PPP1R3C; human.
DR GeneWiki; PPP1R3C; -.
DR GenomeRNAi; 5507; -.
DR Pharos; Q9UQK1; Tbio.
DR PRO; PR:Q9UQK1; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UQK1; protein.
DR Bgee; ENSG00000119938; Expressed in skeletal muscle tissue of rectus abdominis and 199 other tissues.
DR Genevisible; Q9UQK1; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IBA:GO_Central.
DR GO; GO:2001069; F:glycogen binding; IBA:GO_Central.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; ISS:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; TAS:ProtInc.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; ISS:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; IBA:GO_Central.
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_0000285927"
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:0000269|PubMed:14532330"
FT MOTIF 84..87
FT /note="PP1-binding motif"
FT VARIANT 109
FT /note="A -> S (in dbSNP:rs7089948)"
FT /id="VAR_059775"
FT VARIANT 249
FT /note="N -> S (found in a patient with progressive
FT myoclonic epilepsy type 2 also carrying two mutations in
FT EPM2B; dbSNP:rs373998228)"
FT /evidence="ECO:0000269|PubMed:21738631"
FT /id="VAR_067339"
FT MUTAGEN 85
FT /note="V->A: No effect on interaction with EPM2A; when
FT associated with A-87."
FT /evidence="ECO:0000269|PubMed:14532330"
FT MUTAGEN 87
FT /note="F->A: No effect on interaction with EPM2A; when
FT associated with A-85."
FT /evidence="ECO:0000269|PubMed:14532330"
FT MUTAGEN 247
FT /note="D->A: No interaction with EPM2A; when associated
FT with A-250."
FT /evidence="ECO:0000269|PubMed:14532330"
FT MUTAGEN 250
FT /note="D->A: No interaction with EPM2A; when associated
FT with A-247."
FT /evidence="ECO:0000269|PubMed:14532330"
SQ SEQUENCE 317 AA; 36445 MW; FBFD6DE015F9AB2D CRC64;
MSCTRMIQVL DPRPLTSSVM PVDVAMRLCL AHSPPVKSFL GPYDEFQRRH FVNKLKPLKS
CLNIKHKAKS QNDWKCSHNQ AKKRVVFADS KGLSLTAIHV FSDLPEEPAW DLQFDLLDLN
DISSALKHHE EKNLILDFPQ PSTDYLSFRS HFQKNFVCLE NCSLQERTVT GTVKVKNVSF
EKKVQIRITF DSWKNYTDVD CVYMKNVYGG TDSDTFSFAI DLPPVIPTEQ KIEFCISYHA
NGQVFWDNND GQNYRIVHVQ WKPDGVQTQM APQDCAFHQT SPKTELESTI FGSPRLASGL
FPEWQSWGRM ENLASYR
