Q7TMB3 (PPR3C_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein phosphatase 1 regulatory subunit 3C

Alternative name(s):
Protein phosphatase 1 regulatory subunit 5
Short name=PP1 subunit R5
Protein targeting to glycogen
Short name=PTG

Gene names

Name:	Ppp1r3c
Synonyms:	Ppp1r5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	317 AA.
Sequence status	Complete.
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
Post-translational modification	Ubiquitinated by NHLRC1/malin in a EPM2A/laforin-dependent manner By similarity.
Disruption phenotype	Mice 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.
Sequence caution	The sequence AAB49689.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycogen biosynthetic process Inferred from mutant phenotype Ref.9. Source: MGI protein targeting Traceable author statement Ref.9. 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
	Motif	84 – 87	4	PP1-binding motif
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.7 Ref.11
	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.7 Ref.11
	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.7 Ref.11
	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.7 Ref.11
	Sequence conflict	165	1	Q → E in AAB49689. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q7TMB3 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC052769 mRNA. Translation: AAH52769.1. BC054739 mRNA. Translation: AAH54739.1. U89924 mRNA. Translation: AAB49689.1. Different initiation. AK078506 mRNA. Translation: BAC37313.1.
IPI	IPI00308944.
RefSeq	NP_058550.1. NM_016854.2.
UniGene	Mm.24724.
3D structure databases
ProteinModelPortal	Q7TMB3.
SMR	Q7TMB3. Positions 134-262.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000084578.
Protein family/group databases
CAZy	CBM21. Carbohydrate-Binding Module Family 21.
Proteomic databases
PaxDb	Q7TMB3.
PRIDE	Q7TMB3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000087321; ENSMUSP00000084578; ENSMUSG00000067279.
GeneID	53412.
KEGG	mmu:53412.
UCSC	uc008hhs.1. mouse.
Organism-specific databases
CTD	5507.
MGI	MGI:1858229. Ppp1r3c.
Phylogenomic databases
eggNOG	NOG288354.
GeneTree	ENSGT00530000062978.
HOGENOM	HOG000026799.
HOVERGEN	HBG052744.
InParanoid	Q7TMB3.
KO	K07189.
OMA	IVHVQWK.
OrthoDB	EOG4F4SBC.
Gene expression databases
Bgee	Q7TMB3.
Genevestigator	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
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:	May 1, 2013
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program