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   24-JAN-2024, entry version 152.
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   PDB; 7QF7; X-ray; 1.47 A; A=132-264.
DR   PDB; 7QFA; X-ray; 2.00 A; A/B/C=132-264.
DR   PDB; 7QFB; X-ray; 2.05 A; B=81-107.
DR   PDB; 7QM2; X-ray; 2.69 A; B/D=70-264.
DR   PDBsum; 7QF7; -.
DR   PDBsum; 7QFA; -.
DR   PDBsum; 7QFB; -.
DR   PDBsum; 7QM2; -.
DR   AlphaFoldDB; Q9UQK1; -.
DR   SASBDB; 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; 9606-ENSP00000238994; -.
DR   PeptideAtlas; Q9UQK1; -.
DR   ProteomicsDB; 85553; -.
DR   Antibodypedia; 16368; 131 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   AGR; HGNC:9293; -.
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; IVHAQWK; -.
DR   OrthoDB; 3059370at2759; -.
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   SIGNOR; Q9UQK1; -.
DR   BioGRID-ORCS; 5507; 13 hits in 1156 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 201 other cell types or tissues.
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   CDD; cd22815; PBD_PPP1R3C; 1.
DR   Gene3D; 2.60.40.2440; Carbohydrate binding type-21 domain; 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; PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT; 1.
DR   PANTHER; PTHR12307:SF15; PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT 3C; 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.
DR   Genevisible; Q9UQK1; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Carbohydrate metabolism; Glycogen metabolism;
KW   Reference proteome; 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
//