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Protein

Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

Gene

PPP1CC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. 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. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).4 Publications

Miscellaneous

Microcystin toxin is bound to Cys-273 through a thioether bond.

Caution

Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).2 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.1 Publication

Cofactori

Mn2+2 PublicationsNote: Binds 2 manganese ions per subunit.2 Publications

Enzyme regulationi

Inactivated by binding to URI1. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi64Manganese 12 Publications1
Metal bindingi66Manganese 12 Publications1
Metal bindingi92Manganese 12 Publications1
Metal bindingi92Manganese 22 Publications1
Metal bindingi124Manganese 22 Publications1
Active sitei125Proton donor1 Publication1
Metal bindingi173Manganese 22 Publications1
Metal bindingi248Manganese 22 Publications1
Sitei273Inhibition by microcystin toxin binding1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processBiological rhythms, Carbohydrate metabolism, Cell cycle, Cell division, Glycogen metabolism
LigandManganese, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.3.16 2681
ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163560 Triglyceride catabolism
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-400253 Circadian Clock
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-68877 Mitotic Prometaphase
SignaLinkiP36873
SIGNORiP36873

Protein family/group databases

MoonDBiP36873 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (EC:3.1.3.16)
Short name:
PP-1G
Alternative name(s):
Protein phosphatase 1C catalytic subunit
Gene namesi
Name:PPP1CC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000186298.11
HGNCiHGNC:9283 PPP1CC
MIMi176914 gene
neXtProtiNX_P36873

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Kinetochore, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi125H → A: Loss of activity. 1 Publication1
Mutagenesisi273C → A, S or L: Abolishes interaction with microcystin toxin. 1 Publication1

Organism-specific databases

DisGeNETi5501
OpenTargetsiENSG00000186298
PharmGKBiPA33611

Chemistry databases

ChEMBLiCHEMBL4438
DrugBankiDB02860 Calyculin A
DB04738 Motuporin

Polymorphism and mutation databases

BioMutaiPPP1CC
DMDMi548573

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000587872 – 323Serine/threonine-protein phosphatase PP1-gamma catalytic subunitAdd BLAST322

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources2 Publications1
Modified residuei307PhosphothreonineCombined sources1
Modified residuei311PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by NEK2.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP36873
MaxQBiP36873
PaxDbiP36873
PeptideAtlasiP36873
PRIDEiP36873
ProteomicsDBi55224
55225 [P36873-2]
TopDownProteomicsiP36873-1 [P36873-1]
P36873-2 [P36873-2]

PTM databases

CarbonylDBiP36873
DEPODiP36873
iPTMnetiP36873
PhosphoSitePlusiP36873
SwissPalmiP36873

Expressioni

Inductioni

Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.1 Publication

Gene expression databases

BgeeiENSG00000186298
CleanExiHS_PPP1CC
ExpressionAtlasiP36873 baseline and differential
GenevisibleiP36873 HS

Organism-specific databases

HPAiCAB022645

Interactioni

Subunit structurei

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 (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with cyanobacterial toxin microcystin; disulfide-linked. Interacts with PPP1R3B and PPP1R7. Isoform 2 interacts with SPZ1 (By similarity). 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. Interacts with PPP1R42; the interaction is direct (By similarity). Interacts with NOM1 and PPP1R8. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with isoform 1 and isoform 4 NEK2. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts with FOXP3. Interacts with TMEM225 (via RVxF motif) (By similarity). Interacts with MKI67 (PubMed:24867636). Interacts with RRP1B; this targets PPP1CC to the nucleolus (PubMed:20926688). Interacts with PPP1R2B (PubMed:23506001). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).By similarity18 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • lamin binding Source: Ensembl
  • protein C-terminus binding Source: Ensembl
  • protein domain specific binding Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • protein N-terminus binding Source: MGI
  • protein phosphatase 1 binding Source: Ensembl

Protein-protein interaction databases

BioGridi111495, 307 interactors
DIPiDIP-749N
IntActiP36873, 232 interactors
MINTiP36873
STRINGi9606.ENSP00000335084

Chemistry databases

BindingDBiP36873

Structurei

Secondary structure

1323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 17Combined sources9
Helixi18 – 21Combined sources4
Helixi32 – 48Combined sources17
Beta strandi51 – 55Combined sources5
Beta strandi57 – 62Combined sources6
Helixi69 – 79Combined sources11
Beta strandi87 – 89Combined sources3
Beta strandi94 – 98Combined sources5
Helixi100 – 113Combined sources14
Turni115 – 117Combined sources3
Beta strandi118 – 120Combined sources3
Helixi128 – 131Combined sources4
Turni132 – 135Combined sources4
Helixi136 – 143Combined sources8
Helixi146 – 156Combined sources11
Beta strandi162 – 165Combined sources4
Turni166 – 168Combined sources3
Beta strandi169 – 174Combined sources6
Helixi183 – 187Combined sources5
Beta strandi197 – 199Combined sources3
Helixi200 – 206Combined sources7
Beta strandi214 – 218Combined sources5
Beta strandi222 – 227Combined sources6
Helixi229 – 239Combined sources11
Beta strandi243 – 246Combined sources4
Beta strandi254 – 258Combined sources5
Turni259 – 262Combined sources4
Beta strandi263 – 267Combined sources5
Helixi272 – 274Combined sources3
Beta strandi280 – 285Combined sources6
Beta strandi290 – 298Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IT6X-ray2.00A/B1-323[»]
1JK7X-ray1.90A1-323[»]
1U32X-ray2.00A6-298[»]
2BCDX-ray2.10A1-323[»]
2BDXX-ray2.30A1-323[»]
4UT2X-ray1.96A/B1-323[»]
4UT3X-ray2.19A/B1-323[»]
5INBX-ray1.30A7-308[»]
5J28X-ray2.00A/B7-308[»]
ProteinModelPortaliP36873
SMRiP36873
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP36873

Family & Domainsi

Sequence similaritiesi

Belongs to the PPP phosphatase family. PP-1 subfamily.Curated

Phylogenomic databases

eggNOGiENOG410IN85 Eukaryota
ENOG410XPVF LUCA
GeneTreeiENSGT00530000062911
HOGENOMiHOG000172697
HOVERGENiHBG000216
InParanoidiP36873
KOiK06269
OMAiQRGYEFF
OrthoDBiEOG091G0EKF
PhylomeDBiP36873
TreeFamiTF354243

Family and domain databases

Gene3Di3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843 Calcineurin-like_PHP_ApaH
IPR029052 Metallo-depent_PP-like
IPR037981 PPP1CC
IPR006186 Ser/Thr-sp_prot-phosphatase
IPR031675 STPPase_N
PANTHERiPTHR11668:SF204 PTHR11668:SF204, 1 hit
PfamiView protein in Pfam
PF00149 Metallophos, 1 hit
PF16891 STPPase_N, 1 hit
PRINTSiPR00114 STPHPHTASE
SMARTiView protein in SMART
SM00156 PP2Ac, 1 hit
PROSITEiView protein in PROSITE
PS00125 SER_THR_PHOSPHATASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P36873-1) [UniParc]FASTAAdd to basket
Also known as: PPPCC1, Gamma-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.

« Hide

        10         20         30         40         50
MADLDKLNID SIIQRLLEVR GSKPGKNVQL QENEIRGLCL KSREIFLSQP
60 70 80 90 100
ILLELEAPLK ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS
110 120 130 140 150
LETICLLLAY KIKYPENFFL LRGNHECASI NRIYGFYDEC KRRYNIKLWK
160 170 180 190 200
TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL QSMEQIRRIM RPTDVPDQGL
210 220 230 240 250
LCDLLWSDPD KDVLGWGEND RGVSFTFGAE VVAKFLHKHD LDLICRAHQV
260 270 280 290 300
VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAE
310 320
KKKPNATRPV TPPRGMITKQ AKK
Length:323
Mass (Da):36,984
Last modified:June 1, 1994 - v1
Checksum:i0EEEF0E842188536
GO
Isoform 2 (identifier: P36873-2) [UniParc]FASTAAdd to basket
Also known as: PPPCC2, Gamma-2

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

Show »
Length:337
Mass (Da):38,518
Checksum:i9731E5A6C8EEBF46
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051734152F → S. Corresponds to variant dbSNP:rs11558237Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005094315 – 323GMITKQAKK → VASGLNPSIQKASNYRNNTV LYE in isoform 2. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74008 mRNA Translation: CAA52169.1
BC014073 mRNA Translation: AAH14073.1
L07395 mRNA Translation: AAA19823.1
CCDSiCCDS58279.1 [P36873-2]
CCDS9150.1 [P36873-1]
PIRiS35699
S35700
RefSeqiNP_001231903.1, NM_001244974.1 [P36873-2]
NP_002701.1, NM_002710.3 [P36873-1]
UniGeneiHs.79081

Genome annotation databases

EnsembliENST00000335007; ENSP00000335084; ENSG00000186298 [P36873-1]
ENST00000340766; ENSP00000341779; ENSG00000186298 [P36873-2]
GeneIDi5501
KEGGihsa:5501
UCSCiuc001tru.4 human [P36873-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPP1G_HUMAN
AccessioniPrimary (citable) accession number: P36873
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 20, 2018
This is version 213 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

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