Reviewed, UniProtKB/Swiss-Prot P36873 (PP1G_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
      Short name=PP-1G
    EC=3.1.3.16
Alternative name(s):
    Protein phosphatase 1C catalytic subunit

Gene names

Name:

PPP1CC

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca2+/calmodulin dependent protein kinase II.
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 iron ion per subunit. Binds 1 manganese ion per subunit.
Enzyme regulation	The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress. Ref.9
Subunit structure	PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A, PPP1R3B, PPP1R3C and PPP1R3D mediate binding to glycogen. Interacts with cyanobacterial toxin microcystin; disulfide-linked. Interacts with PPP1R3B and PPP1R7. Isoform gamma-2 interacts with SPZ1 By similarity. Component of the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with CDCA2. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation By similarity.
Subcellular location	Cytoplasm. Nucleus By similarity. Note: Colocalizes with SPZ1 in the nucleus By similarity.
Miscellaneous	Microcystin toxin is bound to Cys-273 through a thioether bond.
Sequence similarities	Belongs to the PPP phosphatase family. PP-1 subfamily.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Cell cycle Cell division Glycogen metabolism
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW glycogen metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	MLL5-L complex Ref.13 Inferred from direct assay. Source: UniProtKB
Molecular function	iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase binding Inferred from physical interaction. Source: UniProtKB protein serine/threonine phosphatase activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATM	Q13315	1	EBI-356289,EBI-495465
BCL2	P10415	1	EBI-356289,EBI-77694
BCL2L1	Q07817	1	EBI-356289,EBI-78035
BIRC5	O15392	1	EBI-356289,EBI-518823
BRCA1	P38398	2	EBI-356283,EBI-349905
CCND1	P24385	1	EBI-356289,EBI-375001
CCND3	P30281	1	EBI-356289,EBI-375013
CDC2	P06493	1	EBI-356289,EBI-444308
CDC34	P49427	1	EBI-356289,EBI-975634
CDK2	P24941	1	EBI-356289,EBI-375096
CDK4	P11802	1	EBI-356289,EBI-295644
CDKN2A	Q8N726	1	EBI-356289,EBI-625922
EIF2S1	P05198	1	EBI-356289,EBI-1056162
ESR1	P03372	1	EBI-356283,EBI-78473
MAX	P61244	1	EBI-356289,EBI-878388
PCNA	P12004	1	EBI-356289,EBI-358311
SKP1	P63208	1	EBI-356289,EBI-307486
TP53	P04637	2	EBI-356289,EBI-366083

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Gamma-1 (identifier: P36873-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Gamma-2 (identifier: P36873-2)

The sequence of this isoform differs from the canonical sequence as follows:
     315-323: GMITKQAKK → VASGLNPSIQKASNYRNNTVLYE

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 323

322

Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

PRO_0000058787

Sites

Active site

125

1

Proton donor

Metal binding

64

1

Iron

Metal binding

66

1

Iron

Metal binding

92

1

Iron

Metal binding

92

1

Manganese

Metal binding

124

1

Manganese

Metal binding

173

1

Manganese

Metal binding

248

1

Manganese

Site

273

1

Inhibition by microcystin toxin binding

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.3

Modified residue

147

1

N6-acetyllysine Ref.14

Modified residue

307

1

Phosphothreonine Ref.11

Natural variations

Alternative sequence

315 – 323

9

GMITKQAKK → VASGLNPSIQKASNYRNNTV LYE in isoform Gamma-2.

VSP_005094

Natural variant

152

1

F → S: dbSNP rs11558237.

VAR_051734

Experimental info

Mutagenesis

273

1

C → A, S or L: Abolishes interaction with microcystin toxin. Ref.5

Secondary structure

1

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323

Helix Strand Turn

Details...

Helix

9 – 18

10

Turn

19 – 21

3

Helix

32 – 48

17

Beta strand

51 – 55

5

Beta strand

57 – 62

6

Helix

69 – 79

11

Beta strand

87 – 89

3

Beta strand

94 – 98

5

Helix

100 – 113

14

Turn

115 – 117

3

Beta strand

118 – 120

3

Helix

128 – 131

4

Helix

136 – 143

8

Helix

146 – 156

11

Beta strand

162 – 165

4

Turn

166 – 168

3

Beta strand

169 – 174

6

Helix

183 – 187

5

Beta strand

197 – 199

3

Helix

200 – 206

7

Beta strand

214 – 218

5

Beta strand

222 – 227

6

Helix

229 – 239

11

Beta strand

242 – 246

5

Beta strand

254 – 258

5

Turn

259 – 262

4

Beta strand

263 – 267

5

Helix

272 – 274

3

Beta strand

280 – 285

6

Beta strand

291 – 296

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gamma-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 0EEEF0E842188536	FASTA	323	36,984
	10 20 30 40 50 60 MADLDKLNID SIIQRLLEVR GSKPGKNVQL QENEIRGLCL KSREIFLSQP ILLELEAPLK 70 80 90 100 110 120 ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL 130 140 150 160 170 180 LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL 190 200 210 220 230 240 QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVLGWGEND RGVSFTFGAE VVAKFLHKHD 250 260 270 280 290 300 LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAE 310 320 KKKPNATRPV TPPRGMITKQ AKK
	Isoform Gamma-2. Checksum: 9731E5A6C8EEBF46	FASTA	337	38,518
	10 20 30 40 50 60 MADLDKLNID SIIQRLLEVR GSKPGKNVQL QENEIRGLCL KSREIFLSQP ILLELEAPLK 70 80 90 100 110 120 ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL 130 140 150 160 170 180 LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL 190 200 210 220 230 240 QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVLGWGEND RGVSFTFGAE VVAKFLHKHD 250 260 270 280 290 300 LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAE 310 320 330 KKKPNATRPV TPPRVASGLN PSIQKASNYR NNTVLYE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of human protein serine/threonine phosphatase 1 gamma and localization of the gene (PPP1CC) encoding it to chromosome bands 12q24.1-q24.2." Barker H.M., Craig S.P., Spurr N.K., Cohen P.T.W. Biochim. Biophys. Acta 1178:228-233(1993) [PubMed: 8394140] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA-1 AND GAMMA-2).
[2]	"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] (ISOFORM GAMMA-1). Tissue: Placenta.
[3]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15; 44-60; 99-122; 151-168 AND 247-260, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[4]	"Molecular cloning and chromosomal localization of a human skeletal muscle PP-1 gamma 1 cDNA." Norman S.A., Mott D.M. Mamm. Genome 5:41-45(1994) [PubMed: 8111128] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-323 (ISOFORM GAMMA-1). Tissue: Skeletal muscle.
[5]	"The cyanobacterial toxin microcystin binds covalently to cysteine-273 on protein phosphatase 1." MacKintosh R.W., Dalby K.N., Campbell D.G., Cohen P.T.W., Cohen P., MacKintosh C. FEBS Lett. 371:236-240(1995) [PubMed: 7556599] [Abstract] Cited for: INTERACTION WITH MICROCYSTIN, MUTAGENESIS OF CYS-273.
[6]	"PPP1R6, a novel member of the family of glycogen-targeting subunits of protein phosphatase 1." Armstrong C.G., Browne G.J., Cohen P., Cohen P.T.W. FEBS Lett. 418:210-214(1997) [PubMed: 9414128] [Abstract] Cited for: INTERACTION WITH PPP1R3D.
[7]	"Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1." Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S. Mol. Cell. Biol. 21:6841-6850(2001) [PubMed: 11564868] [Abstract] Cited for: INTERACTION WITH PPP1R15A.
[8]	"Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1." Ceulemans H., Vulsteke V., De Maeyer M., Tatchell K., Stalmans W., Bollen M. J. Biol. Chem. 277:47331-47337(2002) [PubMed: 12226088] [Abstract] Cited for: INTERACTION WITH PPP1R7.
[9]	"A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress." Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D., Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J. Science 307:935-939(2005) [PubMed: 15705855] [Abstract] Cited for: ENZYME REGULATION.
[10]	"Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability." Trinkle-Mulcahy L., Andersen J., Lam Y.W., Moorhead G., Mann M., Lamond A.I. J. Cell Biol. 172:679-692(2006) [PubMed: 16492807] [Abstract] Cited for: INTERACTION WITH CDCA2.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-307, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis." Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S. Nature 459:455-459(2009) [PubMed: 19377461] [Abstract] Cited for: IDENTIFICATION IN THE MLL5-L COMPLEX.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147, MASS SPECTROMETRY.
[15]	"Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate." Egloff M.-P., Cohen P.T.W., Reinemer P., Barford D. J. Mol. Biol. 254:942-959(1995) [PubMed: 7500362] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Protein Spotlight

The things we forget - Issue 32 of March 2003

Cross-references

Sequence databases

EMBLGenBankDDBJ

X74008 mRNA. Translation: CAA52169.1.
BC014073 mRNA. Translation: AAH14073.1.
L07395 mRNA. Translation: AAA19823.1.

IPI

IPI00005705.
IPI00218187.

PIR

S35699.
S35700.

RefSeq

NP_002701.1.

UniGene

Hs.79081

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IT6	X-ray	2.00	A/B	1-323	[»]
1JK7	X-ray	1.90	A	1-323	[»]
1U32	X-ray	2.00	A	6-298	[»]
2BCD	X-ray	2.10	A	1-323	[»]
2BDX	X-ray	2.30	A	1-323	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:749N.

IntAct

P36873. 22 interactions.

STRING

P36873.

PTM databases

PhosphoSite

P36873.

Proteomic databases

PRIDE

P36873.

Genome annotation databases

Ensembl

ENST00000335007; ENSP00000335084; ENSG00000186298; Homo sapiens. [Genome view]
ENST00000340766; ENSP00000341779; ENSG00000186298; Homo sapiens. [Genome view]

GeneID

5501.

KEGG

hsa:5501.

UCSC

uc001tru.1. human.

Organism-specific databases

CTD

5501.

GeneCards

GC12M109620.

H-InvDB

HIX0019358.

HGNC

HGNC:9283. PPP1CC.

HPA

CAB022645.

MIM

176914. gene.

PharmGKB

PA33611.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P36873.

OMA

MITKQAK.

Enzyme and pathway databases

BRENDA

3.1.3.16. 247.

Pathway_Interaction_DB

aurora_b_pathway. Aurora B signaling.
insulin_glucose_pathway. Insulin-mediated glucose transport.

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P36873.

Bgee

P36873.

CleanEx

HS_PPP1CC.

Genevestigator

P36873.

GermOnline

ENSG00000186298. Homo sapiens.

Family and domain databases

InterPro

IPR004843. M-pesterase.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]

PANTHER

PTHR11668. T_phtase_apaH. 1 hit.

Pfam

PF00149. Metallophos. 1 hit.
[Graphical view]

PRINTS

PR00114. STPHPHTASE.

ProDom

PD000252. T_phtase_apaH. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00156. PP2Ac. 1 hit.
[Graphical view]

PROSITE

PS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

21286.

SOURCE

Search...

Entry information

Entry name

PP1G_HUMAN

Accession

Primary (citable) accession number: P36873

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	November 3, 2009
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.