Reviewed, UniProtKB/Swiss-Prot Q7TMB3 (PPR3C_MOUSE)

Names and origin

Protein names

Recommended name:
    Protein phosphatase 1 regulatory subunit 3C
Alternative name(s):
    Protein phosphatase 1 regulatory subunit 5
      Short name=R5
    Protein targeting to glycogen
      Short name=PTG

Gene names

Name:	Ppp1r3c
Synonyms:	Ppp1r5

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	317 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown. Dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression in a variety of cell types. Ref.2 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Subunit structure	Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity. Also interacts with EPM2A/laforin. Ref.2 Ref.12
Domain	The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase, glycogen synthase and phosphorylase kinase. Ref.11
Miscellaneous	Mice lacking Ppp1r3c display embryonic lethality when homozygous. Heterozygotes display decreased protein levels, decreased glycogen accumulation and glycogen synthase activity, reduced insulin-stimulated glycogen synthesis and progressive age-dependent glucose intolerance. When Ppp1r3c is silenced in adults, they display decreased PP1 activity and glycogen accumulation, increased phosphorylation of glycogen phosphorylase, increased GLUT1 levels, increased glucose uptake and increased glycogen degradation. Ref.11 Ref.13
Sequence similarities	Contains 1 CBM21 (carbohydrate binding type-21) domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
Gene Ontology (GO)
Biological process	glycogen biosynthetic process Ref.9 Inferred from mutant phenotype. Source: MGI protein targeting Ref.9 Traceable author statement. Source: MGI
Molecular function	protein binding Ref.9 Traceable author statement. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 317	317	Protein phosphatase 1 regulatory subunit 3C		PRO_0000285928
Regions
	Domain	149 – 257	109	CBM21
	Region	141 – 263	123	Interaction with EPM2A By similarity Ref.12
Experimental info
	Mutagenesis	85	1	V → A: Abolishes binding to PP1 but has no effect on binding to glycogen synthase, glycogen phosphorylase or glycogen; when associated with A-87 Ref.11 Ref.7
	Mutagenesis	87	1	F → A: Abolishes binding to PP1 but has no effect on binding to glycogen synthase, glycogen phosphorylase or glycogen; when associated with A-85 Ref.11 Ref.7
	Mutagenesis	247	1	D → A: Abolishes binding to glycogen synthase and glycogen phosphorylase but has no effect on binding to PP1 or glycogen; when associated with A-250 Ref.11 Ref.7
	Mutagenesis	250	1	E → A: Abolishes binding to glycogen synthase and glycogen phosphorylase but has no effect on binding to PP1 or glycogen; when associated with A-247 Ref.11 Ref.7
	Sequence conflict	165	1	Q → E in AAB49689. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q7TMB3-1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 8DC8941B733649D6	FASTA	317	36,460
	10 20 30 40 50 60 MSCTRMIHVL DPRPLTSSVM PVDMAMRICL AHSPPLKSFL GPYNGFQRRN FVNKLKPLKP 70 80 90 100 110 120 CLSVKQEAKS QSEWKSPHNQ AKKRVVFADS KGLSLTAIHV FSDLPEEPAW DLQFDLLDLN 130 140 150 160 170 180 DISSSLKLHE EKNLVFDFPQ PSTDYLSFRD RFQKNFVCLE NCSLQDRTVT GTVKVKNVSF 190 200 210 220 230 240 EKKVQVRITF DTWKTYTDVD CVYMKNVYSS SDSDTFSFAI DLPRVIPTEE KIEFCISYHA 250 260 270 280 290 300 NGRIFWDNNE GQNYRIVHVQ WKPDGVQTQV APKDCAFQQG PPKTEIEPTV FGSPRLASGL 310 FPEWQSWGRV ENLTSYR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain and Olfactory epithelium.
[2]	"PTG, a protein phosphatase 1-binding protein with a role in glycogen metabolism." Printen J.A., Brady M.J., Saltiel A.R. Science 275:1475-1478(1997) [PubMed: 9045612] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-317, FUNCTION, ASSOCIATION WITH GLYCOGEN, INTERACTION WITH PPP1CC.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 126-317. Strain: C57BL/6J. Tissue: Muellerian duct.
[4]	"Role of protein targeting to glycogen (PTG) in the regulation of protein phosphatase-1 activity." Brady M.J., Printen J.A., Mastick C.C., Saltiel A.R. J. Biol. Chem. 272:20198-20204(1997) [PubMed: 9242697] [Abstract] Cited for: FUNCTION.
[5]	"Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms." Berman H.K., O'Doherty R.M., Anderson P., Newgard C.B. J. Biol. Chem. 273:26421-26425(1998) [PubMed: 9756875] [Abstract] Cited for: FUNCTION.
[6]	"Distinctive regulatory and metabolic properties of glycogen-targeting subunits of protein phosphatase-1 (PTG, GL, GM/RGl) expressed in hepatocytes." Gasa R., Jensen P.B., Berman H.K., Brady M.J., DePaoli-Roach A.A., Newgard C.B. J. Biol. Chem. 275:26396-26403(2000) [PubMed: 10862764] [Abstract] Cited for: FUNCTION.
[7]	"Identification of binding sites on protein targeting to glycogen for enzymes of glycogen metabolism." Fong N.M., Jensen T.C., Shah A.S., Parekh N.N., Saltiel A.R., Brady M.J. J. Biol. Chem. 275:35034-35039(2000) [PubMed: 10938087] [Abstract] Cited for: MUTAGENESIS OF VAL-85; PHE-87; ASP-247 AND GLU-250.
[8]	"Overexpression of protein targeting to glycogen in cultured human muscle cells stimulates glycogen synthesis independent of glycogen and glucose 6-phosphate levels." Lerin C., Montell E., Berman H.K., Newgard C.B., Gomez-Foix A.M. J. Biol. Chem. 275:39991-39995(2000) [PubMed: 10998419] [Abstract] Cited for: FUNCTION.
[9]	"Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen." O'Doherty R.M., Jensen P.B., Anderson P., Jones J.G., Berman H.K., Kearney D., Newgard C.B. J. Clin. Invest. 105:479-488(2000) [PubMed: 10683377] [Abstract] Cited for: FUNCTION.
[10]	"Protein targeting to glycogen overexpression results in the specific enhancement of glycogen storage in 3T3-L1 adipocytes." Greenberg C.C., Meredith K.N., Yan L., Brady M.J. J. Biol. Chem. 278:30835-30842(2003) [PubMed: 12805359] [Abstract] Cited for: FUNCTION.
[11]	"PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance." Crosson S.M., Khan A., Printen J., Pessin J.E., Saltiel A.R. J. Clin. Invest. 111:1423-1432(2003) [PubMed: 12727934] [Abstract] Cited for: FUNCTION, NULL MUTANT.
[12]	"The glycogenic action of protein targeting to glycogen in hepatocytes involves multiple mechanisms including phosphorylase inactivation and glycogen synthase translocation." Green A.R., Aiston S., Greenberg C.C., Freeman S., Poucher S.M., Brady M.J., Agius L. J. Biol. Chem. 279:46474-46482(2004) [PubMed: 15322104] [Abstract] Cited for: FUNCTION.
[13]	"Central role for protein targeting to glycogen in the maintenance of cellular glycogen stores in 3T3-L1 adipocytes." Greenberg C.C., Danos A.M., Brady M.J. Mol. Cell. Biol. 26:334-342(2006) [PubMed: 16354703] [Abstract] Cited for: FUNCTION, NULL MUTANT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC052769 mRNA. Translation: AAH52769.1. BC054739 mRNA. Translation: AAH54739.1. U89924 mRNA. Translation: AAB49689.1. Different initiation. AK078506 mRNA. Translation: BAC37313.1.
RefSeq	NP_058550.1.
UniGene	Mm.24724
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000067279. Mus musculus. [Contig view]
GeneID	53412.
KEGG	mmu:53412.
Organism-specific databases
MGI	MGI:1858229. Ppp1r3c.
Phylogenomic databases
HOVERGEN	Q7TMB3.
Gene expression databases
ArrayExpress	Q7TMB3.
Family and domain databases
InterPro	IPR005036. CBM_21. IPR017434. Pase-1_Glycogen_target-su_met. [Graphical view]
Pfam	PF03370. CBM_21. 1 hit. [Graphical view]
PIRSF	PIRSF038207. PP1_GT_animal. 1 hit.
PROSITE	PS51159. CBM21. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	310221.
SOURCE	Search...

Entry information

Entry name

PPR3C_MOUSE

Accession

Primary (citable) accession number: Q7TMB3
Secondary accession number(s): O08541, Q8BJW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	October 1, 2003
Last modified:	November 4, 2008
This is version 29 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)