PPP1CC

Summary

PPP1CC (protein phosphatase 1 catalytic subunit gamma, HGNC:9283) is a protein-coding gene on chromosome 12q24.11, encoding Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (P36873). Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets.

The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5501 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9283
Approved symbol	PPP1CC
Name	protein phosphatase 1 catalytic subunit gamma
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	PP1C, PP1gamma
Ensembl gene	ENSG00000186298
Ensembl biotype	protein_coding
OMIM	176914
Entrez	5501

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 non_stop_decay

ENST00000335007, ENST00000340766, ENST00000546904, ENST00000546933, ENST00000550261, ENST00000550991, ENST00000551582, ENST00000551676, ENST00000551690, ENST00000553024, ENST00000620030

RefSeq mRNA: 2 — MANE Select: NM_002710 NM_001244974, NM_002710

CCDS: CCDS58279, CCDS9150

Canonical transcript exons

ENST00000335007 — 7 exons

Exon	Start	End
ENSE00001332986	110731770	110731901
ENSE00001408003	110719680	110721165
ENSE00001783751	110730529	110730759
ENSE00001804069	110724660	110724764
ENSE00002365063	110742653	110742891
ENSE00003610831	110722135	110722269
ENSE00003630337	110722472	110722695

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.5351 / max 487.3277, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133269	45.5865	1825
206895	1.9485	1153

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.65	gold quality
heart right ventricle	UBERON:0002080	99.46	gold quality
parotid gland	UBERON:0001831	99.38	gold quality
adult organism	UBERON:0007023	99.26	gold quality
jejunum	UBERON:0002115	99.25	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.20	gold quality
biceps brachii	UBERON:0001507	99.16	gold quality
secondary oocyte	CL:0000655	99.11	gold quality
superficial temporal artery	UBERON:0001614	99.06	gold quality
duodenum	UBERON:0002114	99.03	gold quality
male germ cell	CL:0000015	99.00	gold quality
skin of hip	UBERON:0001554	99.00	gold quality
sperm	CL:0000019	98.99	gold quality
oral cavity	UBERON:0000167	98.97	gold quality
germinal epithelium of ovary	UBERON:0001304	98.97	gold quality
esophagus squamous epithelium	UBERON:0006920	98.93	gold quality
tibia	UBERON:0000979	98.86	gold quality
colonic mucosa	UBERON:0000317	98.83	gold quality
upper leg skin	UBERON:0004262	98.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.80	gold quality
gluteal muscle	UBERON:0002000	98.72	gold quality
choroid plexus epithelium	UBERON:0003911	98.67	gold quality
ventricular zone	UBERON:0003053	98.63	gold quality
synovial joint	UBERON:0002217	98.57	gold quality
parietal pleura	UBERON:0002400	98.57	gold quality
pigmented layer of retina	UBERON:0001782	98.52	gold quality
embryo	UBERON:0000922	98.51	gold quality
pleura	UBERON:0000977	98.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.51	gold quality
penis	UBERON:0000989	98.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.48
E-HCAD-11	yes	7.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CXXC1, HNRNPK, JARID2, NCOA3, POU5F1, SP1, SP3, TFCP2

miRNA regulators (miRDB)

22 targeting PPP1CC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-8071	95.69	64.93	484
HSA-MIR-7109-3P	94.23	67.19	743

Literature-anchored findings (GeneRIF, showing 36)

• gamma isoform of the human protein phosphatase-1 catalytic subunit (PP1c gamma) as a high affinity in vitro target of phosphatidic acid (PMID:11856740)
• Nek2.PP1C complex is regulated by Inh2 via inhibition of phosphatase activity to initiate centrosome separation (PMID:12221103)
• Tat might function as a nuclear regulator of PP1 and interaction of Tat with PP1 is critical for activation of HIV-1 transcription by Tat (PMID:16131488)
• analysis of novel phosphatidic acid (PA) binding region on PP1c gamma that contains a unique loop-strand structural fold responsible for the interaction with PA (PMID:16201749)
• crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (PMID:16343532)
• We demonstrate that interaction with NIPP1 mediates decreased PP1gamma activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia. (PMID:16826568)
• Data show that URI and PP1gamma are components of an S6K1-regulated mitochondrial pathway dedicated to oppose sustained S6K1 survival signaling and to ensure that the threshold for apoptosis is set based on nutrient and growth factor availability. (PMID:17936702)
• Results describe a specific intracellular pathway involving the activation of PP1cgamma to mediate the effects of confluence-induced beta-catenin dephosphorylation. (PMID:17996206)
• PP1cgamma1 overexpression promotes VSMC survival by interfering with JNK1 and p53 phosphorylation cascades involved in apoptosis (PMID:18540044)
• Protein phosphatase 1 binding occurs through a conserved RVXF motif found in the KH domain of AKAP149. (PMID:19074462)
• mammalian Wdr82 functions in a variety of cellular processes; PTW/PP1 phosphatase complex (PNUTS, Tox4, Wdr82, PP1) has a role in the regulation of chromatin structure during the transition from mitosis into interphase (PMID:20516061)
• The ataxia telangiectasia, mutated and Rad3-related-Chk1 axis regulates H3-pThr 11 dephosphorylation on DNA damage, at least in part by the activation of PP1gamma through Chk1-dependent inhibition of cyclin dependent kinases. (PMID:20948546)
• The counteracting Nek2A and PP1gamma activities on the centrosome linker are controlled by Plk1. (PMID:21723128)
• NUAK1 and PPP1CC are identified as positional candidate loci for skeletal muscle strength phenotypes. (PMID:21750233)
• Depletion of PP1gamma enhances the localization of the SMN complex and snRNPs to Cajal bodies. (PMID:22454514)
• When the Px(T)PxR motif is deleted or mutated via insertion of a phosphorylation site mimic (T311D), PP-1c fails to bind to all three ASPP proteins, ASPP1, ASPP2 and iASPP. (PMID:23088536)
• PP-1alpha and PP-1gamma not only antagonize each other in lung cancer cells, but also display differential functions in tumorigenicity. (PMID:23176181)
• PPP1C isoforms have distinct contribution to the outside-in alphaIIbbeta3 signalling-dependent functions in HEK293 alphaIIbbeta3 cells. (PMID:23197154)
• Findings indicate that phosphatases PP1alpha and PP1gamma are key regulators of RIG-I and MDA5 antiviral signaling. (PMID:23499489)
• Protein phosphatase 1gamma promotes the alternative splicing of CaMKIIdelta through its interaction with alternative splice factor. (PMID:24196533)
• the lipin-1 N-terminal domain is important for its catalytic activity, nuclear localization, and binding to PP-1cgamma (PMID:24558042)
• Although no obvious defects in the progression of mitosis were observed, the timing of dephosphorylation of the mutant Ki67 in anaphase was delayed, indicating that Ki67 itself is one of the substrates of PP1gamma-Ki67. (PMID:25012651)
• PP1gamma may be a novel target of the HPV-16 oncoproteins and indicate that it might be a potential novel biomarker for HPV-16 induced malignancy. (PMID:25886518)
• knock-down of PP1gamma alleviates glioma proliferation by reducing p65 transportation into the nucleus. (PMID:26936744)
• Here the authors show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. (PMID:27572260)
• PP1gamma is upregulated in hepatocellular carcinoma (HCC) cell lines and HCC specimens and promotes cancer cell proliferation through regulation of p53. High expression of PP1gamma in HCC cells contributed to doxorubicin resistance. (PMID:27921263)
• Data suggest that PPP1CC catalyzes hydrolysis of an assortment of substrates (aryl methylphosphonates, fluorophosphate esters, phosphorothioate esters, phosphodiesters); conservative mutation of R221 to K results in a mutant that is more effective catalyst toward monoanionic substrates; PPP1CC does not catalyze the hydrolysis of a sulfate ester, which is unexpected. (PMID:28678475)
• our work has identified both the mechanism of SLFN11 activation and PPP1CC as the enzyme responsible for its activation. Our findings open up future studies of the PPP1CC subunit(s) involved in SLFN11 activation and the putative kinase(s) that inactivates SLFN11. (PMID:31395656)
• Aurora B regulates PP1gamma-Repo-Man interactions to maintain the chromosome condensation state. (PMID:32938714)
• The role of LR-TIMAP/PP1c complex in the occurrence and development of no-reflow. (PMID:33639401)
• Structure of the MRAS-SHOC2-PP1C phosphatase complex. (PMID:35830882)
• Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. (PMID:35831509)
• Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome. (PMID:36175670)
• PP1gamma regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes. (PMID:37085815)
• TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation. (PMID:38139189)
• High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma. (PMID:38589496)

Cross-species orthologs

27 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1cc	ENSDARG00000099226
mus_musculus	Ppp1cc	ENSMUSG00000004455
caenorhabditis_elegans		WBGENE00007354
caenorhabditis_elegans		WBGENE00007699
caenorhabditis_elegans		WBGENE00007700
caenorhabditis_elegans		WBGENE00007763
caenorhabditis_elegans		WBGENE00008124
caenorhabditis_elegans	F22D6.9	WBGENE00009054
caenorhabditis_elegans		WBGENE00009079
caenorhabditis_elegans		WBGENE00009101
caenorhabditis_elegans		WBGENE00009893
caenorhabditis_elegans		WBGENE00010265
caenorhabditis_elegans		WBGENE00011133
caenorhabditis_elegans		WBGENE00012008
caenorhabditis_elegans		WBGENE00012741
caenorhabditis_elegans		WBGENE00013476
caenorhabditis_elegans		WBGENE00014158
caenorhabditis_elegans		WBGENE00016010
caenorhabditis_elegans		WBGENE00016081
caenorhabditis_elegans	F26B1.5	WBGENE00017817
caenorhabditis_elegans		WBGENE00018359
caenorhabditis_elegans		WBGENE00018410
caenorhabditis_elegans		WBGENE00019951
caenorhabditis_elegans	W03D8.2	WBGENE00020985
caenorhabditis_elegans		WBGENE00022617
caenorhabditis_elegans		WBGENE00022710
caenorhabditis_elegans	Y71G12B.30	WBGENE00044347

Paralogs (12): PPP5C (ENSG00000011485), PPEF1 (ENSG00000086717), PPP2CB (ENSG00000104695), PPP3CB (ENSG00000107758), PPP2CA (ENSG00000113575), PPP6C (ENSG00000119414), PPP3CC (ENSG00000120910), PPP3CA (ENSG00000138814), PPP4C (ENSG00000149923), PPEF2 (ENSG00000156194), PPP1CA (ENSG00000172531), PPP1CB (ENSG00000213639)

Protein

Protein identifiers

Serine/threonine-protein phosphatase PP1-gamma catalytic subunit — P36873 (reviewed: P36873)

Alternative names: Protein phosphatase 1C catalytic subunit

All UniProt accessions (7): A0A087WYY5, P36873, F8VR82, F8VYE8, F8W0V8, F8W0W8, F8W1A0

UniProt curated annotations — full annotation on UniProt →

Function. 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 Ca(2+)/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. Regulates the recruitment of the SKA complex to kinetochores. 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. Together with PPP1CA (PP1-alpha subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response. Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation. The SMP complex specifically dephosphorylates the inhibitory phosphorylation at ‘Ser-259’ of RAF1 kinase, ‘Ser-365’ of BRAF kinase and ‘Ser-214’ of ARAF kinase, stimulating their kinase activities. Dephosphorylates MKI67 at the onset of anaphase. The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c.

Subunit / interactions. 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. 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. 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). Interacts with MKI67. Interacts with RRP1B; this targets PPP1CC to the nucleolus. Interacts with PPP1R2B. Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1. Interacts with DYNLT4. Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity. Interacts with the KNL1 complex subunit KNL1; the interaction is direct and mutually exclusive with KNL1 binding to microtubules. Component of the SHOC2-MRAS-PP1c (SMP) complex consisting of SHOC2, GTP-bound M-Ras/MRAS and the catalytic subunit of protein phosphatase 1 (either PPP1CA, PPP1CB or PPP1CC). SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS; these interactions are GTP-dependent and both SHOC2 and PP1c are required to form a stable complex. Interacts with SHOC2 in the absence of Ras GTPases.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm. Nucleus speckle. Chromosome. Centromere. Kinetochore. Cleavage furrow. Midbody. Mitochondrion. Cytoskeleton. Microtubule organizing center.

Post-translational modifications. Phosphorylated by NEK2.

Activity regulation. 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.

Cofactor. Binds 2 manganese ions per subunit.

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

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

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

Isoforms (2)

UniProt ID	Names	Canonical?
P36873-1	1, PPPCC1, Gamma-1	yes
P36873-2	2, PPPCC2, Gamma-2

RefSeq proteins (2): NP_001231903, NP_002701* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006186	Ser/Thr-sp_prot-phosphatase	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR031675	STPPase_N	Domain
IPR050341	PP1_catalytic_subunit	Family

Pfam: PF00149, PF16891

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (53 total): strand 15, helix 13, binding site 8, turn 4, modified residue 3, mutagenesis site 3, initiator methionine 1, chain 1, site 1, splice variant 1, sequence variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5INB	X-RAY DIFFRACTION	1.3
1JK7	X-RAY DIFFRACTION	1.9
4UT2	X-RAY DIFFRACTION	1.96
1IT6	X-RAY DIFFRACTION	2
1U32	X-RAY DIFFRACTION	2
5J28	X-RAY DIFFRACTION	2
2BCD	X-RAY DIFFRACTION	2.1
4UT3	X-RAY DIFFRACTION	2.19
2BDX	X-RAY DIFFRACTION	2.3
7SD0	ELECTRON MICROSCOPY	2.95
8B5R	ELECTRON MICROSCOPY	6.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36873-F1	92.89	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 273 (inhibition by microcystin toxin binding); 125 (proton donor)

Ligand- & substrate-binding residues (8): 173; 248; 64; 64; 66; 92; 92; 124

Post-translational modifications (3): 2, 307, 311

Mutagenesis-validated functional residues (3):

Position	Phenotype
50	promotes smp complex formation.
125	loss of activity.
273	abolishes interaction with microcystin toxin.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-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-5663220	RHO GTPases Activate Formins
R-HSA-5673000	RAF activation
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-9726840	SHOC2 M1731 mutant abolishes MRAS complex function
R-HSA-9726842	Gain-of-function MRAS complexes activate RAF signaling
R-HSA-9828806	Maturation of hRSV A proteins
R-HSA-9931530	Phosphorylation and nuclear translocation of the CRY:PER:kinase complex

MSigDB gene sets: 443 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_CIRCADIAN_RHYTHM, REACTOME_TRIGLYCERIDE_CATABOLISM, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MOOTHA_GLYCOGEN_METABOLISM, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, MORF_ESPL1, MORF_BUB1, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_PHOTOPERIODISM, GCM_NPM1

GO Biological Process (14): mitotic sister chromatid segregation (GO:0000070), MAPK cascade (GO:0000165), blastocyst development (GO:0001824), glycogen metabolic process (GO:0005977), protein dephosphorylation (GO:0006470), spermatogenesis (GO:0007283), neuron differentiation (GO:0030182), circadian regulation of gene expression (GO:0032922), regulation of circadian rhythm (GO:0042752), entrainment of circadian clock by photoperiod (GO:0043153), regulation of nucleocytoplasmic transport (GO:0046822), cell division (GO:0051301), positive regulation of glial cell proliferation (GO:0060252), rhythmic process (GO:0048511)

GO Molecular Function (13): RNA binding (GO:0003723), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), lamin binding (GO:0005521), protein phosphatase 1 binding (GO:0008157), phosphatase activity (GO:0016791), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787), protein phosphatase binding (GO:0019903)

GO Cellular Component (23): kinetochore (GO:0000776), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), microtubule organizing center (GO:0005815), cytosol (GO:0005829), focal adhesion (GO:0005925), nuclear speck (GO:0016607), midbody (GO:0030496), cleavage furrow (GO:0032154), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), PTW/PP1 phosphatase complex (GO:0072357), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), chromosome, centromeric region (GO:0000775), chromosome, telomeric region (GO:0000781), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytoskeleton (GO:0005856), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Mitotic Prometaphase	2
Signaling by MRAS-complex mutants	2
Amplification of signal from the kinetochores	1
Triglyceride metabolism	1
TGF-beta receptor signaling activates SMADs	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
RAF/MAP kinase cascade	1
M Phase	1
Respiratory syncytial virus (RSV) genome replication, transcription and translation	1
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
circadian rhythm	2
protein binding	2
binding	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cytoplasm	2
synapse	2
chromosomal region	2
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
intracellular signaling cassette	1
in utero embryonic development	1
anatomical structure development	1
energy reserve metabolic process	1
glucan metabolic process	1
dephosphorylation	1
protein modification process	1
developmental process involved in reproduction	1
male gamete generation	1
cell differentiation	1
generation of neurons	1
regulation of gene expression	1
regulation of biological process	1
photoperiodism	1
entrainment of circadian clock	1
nucleocytoplasmic transport	1
regulation of intracellular transport	1
cellular process	1
positive regulation of cell population proliferation	1
glial cell proliferation	1
positive regulation of gliogenesis	1
regulation of glial cell proliferation	1
biological_process	1
nucleic acid binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1

Protein interactions and networks

STRING

6118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1CC	PPP1R12A	O14974	991
PPP1CC	PPP1R15A	O75807	990
PPP1CC	CDCA2	Q69YH5	961
PPP1CC	PPP1R15B	Q5SWA1	931
PPP1CC	SHOC2	Q9UQ13	919
PPP1CC	PPP1R9B	Q96SB3	904
PPP1CC	PPP1R7	Q15435	897
PPP1CC	PPP1CA	P08129	853
PPP1CC	AURKB	Q96GD4	847
PPP1CC	DDX4	Q9NQI0	831
PPP1CC	DDX3Y	O15523	815
PPP1CC	BRCA1	P38398	813
PPP1CC	KNL1	Q8NG31	789
PPP1CC	PPP1CB	P37140	783
PPP1CC	CENPC	Q03188	782

IntAct

268 interactions, top by confidence:

A	B	Type	Score
ZWINT	NDC80	psi-mi:“MI:0914”(association)	0.940
PPP1CC	TP53BP2	psi-mi:“MI:0915”(physical association)	0.920
URI1	PPP1CC	psi-mi:“MI:0915”(physical association)	0.910
PPP1CC	URI1	psi-mi:“MI:0915”(physical association)	0.910
PPP1R7	PPP1CC	psi-mi:“MI:0914”(association)	0.890
RRP1B	PPP1CC	psi-mi:“MI:0915”(physical association)	0.880
PPP1CC	RRP1B	psi-mi:“MI:0407”(direct interaction)	0.880
PPP1CC	RRP1B	psi-mi:“MI:0403”(colocalization)	0.880
RRP1B	PPP1CC	psi-mi:“MI:0914”(association)	0.880
RRP1B	PPP1CC	psi-mi:“MI:0403”(colocalization)	0.880
PPP1CC	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.860
PPP1CC	LMTK2	psi-mi:“MI:0915”(physical association)	0.860
PPP1CC	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.850
ZFYVE9	PPP1CC	psi-mi:“MI:0915”(physical association)	0.850
PPP1CA	PPP1CC	psi-mi:“MI:0914”(association)	0.850
PPP1R11	PPP1CC	psi-mi:“MI:0915”(physical association)	0.850
CSRNP2	PPP1CC	psi-mi:“MI:0915”(physical association)	0.830
PPP1CC	CSRNP2	psi-mi:“MI:0915”(physical association)	0.830
SCRIB	ADRA1D	psi-mi:“MI:0914”(association)	0.820
DNAAF10	PPP1CC	psi-mi:“MI:0914”(association)	0.800
PPP1CC	CSRNP1	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (1319): TP53BP2 (Two-hybrid), ZFYVE9 (Two-hybrid), CD2BP2 (Two-hybrid), CSRNP1 (Two-hybrid), CSRNP2 (Two-hybrid), PPP1CC (Affinity Capture-MS), PPP1CC (Affinity Capture-MS), PPP1CC (Two-hybrid), PPP1CC (Two-hybrid), PPP1CC (Two-hybrid), PPP1CC (Two-hybrid), RORC (Two-hybrid), PPP1CC (Two-hybrid), CLOCK (Affinity Capture-Luminescence), PPP1CC (Affinity Capture-MS)

ESM2 similar proteins: A0C1E4, A0CCD2, A0CNL9, A0DJ90, O04860, O04951, O15757, O76932, P11612, P20604, P22198, P23778, P32345, P32598, P36873, P36874, P48461, P48528, P48578, P48726, P49576, P61287, P62136, P62137, P62138, P62139, P63087, P63088, Q06009, Q07099, Q07100, Q10298, Q27884, Q3T0E7, Q54RD6, Q59KY8, Q6BFF6, Q6NVU2, Q74ZR2, Q7SZ10

Diamond homologs: A0C1E4, A0CCD2, A0CNL9, A0DJ90, A2X2G3, A2XN40, A2YEB4, A3C4N5, A6H772, A8WGP3, A8XE00, A9JRC7, G5EGK8, O00743, O04860, O04951, O74789, O76932, P0C5D7, P11084, P11493, P11611, P20604, P23594, P23595, P23635, P23636, P23696, P23778, P32345, P32838, P36614, P36873, P36874, P48463, P48528, P48529, P48577, P48578, P48579

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
PPP1R15A	up-regulates	PPP1CC	binding
PPP1R15A	up-regulates	PPP1CC	relocalization
PPP1CC	down-regulates	TGFBR1	dephosphorylation
PPP1CC	up-regulates	CDK9	dephosphorylation
PPP1CC	up-regulates	IKZF1	dephosphorylation
PPP1CC	“down-regulates activity”	AXIN1	dephosphorylation
PPP1CC	“down-regulates activity”	TP53	dephosphorylation
PPP1CC	“up-regulates activity”	NOS3	dephosphorylation
PPP1CC	“down-regulates activity”	AKT	dephosphorylation
PPP1CC	“up-regulates quantity by stabilization”	MDM2	dephosphorylation
PPP1CC	“down-regulates activity”	AKT1	dephosphorylation
PPP1CC	“up-regulates activity”	EIF2S1	dephosphorylation
PPP1R15A	“up-regulates activity”	PPP1CC	binding
PPP1CC	“up-regulates activity”	IFIH1	dephosphorylation
PPP1CC	“up-regulates activity”	DDX58	dephosphorylation
PPP1R1B	“down-regulates activity”	PPP1CC	binding
CDCA2	“up-regulates activity”	PPP1CC	binding
NEK2	down-regulates	PPP1CC	phosphorylation
PPP1CC	unknown	AHCYL1	dephosphorylation
PPP1CC	“up-regulates activity”	CASP2	dephosphorylation
ANKRD28	“up-regulates activity”	PPP1CC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	5	15.1×	8e-03
mitophagy	5	13.7×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

27 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1022 predictions. Top by Δscore:

Variant	Effect	Δscore
12:110722170:T:C	donor_gain	1.0000
12:110722529:TTCTG:T	donor_gain	1.0000
12:110722530:TCTGC:T	donor_gain	1.0000
12:110722691:TAAAC:T	acceptor_gain	1.0000
12:110722692:AAAC:A	acceptor_gain	1.0000
12:110722693:AAC:A	acceptor_gain	1.0000
12:110722694:AC:A	acceptor_gain	1.0000
12:110722695:CC:C	acceptor_gain	1.0000
12:110722696:C:CC	acceptor_gain	1.0000
12:110722703:A:AC	acceptor_gain	1.0000
12:110724656:CTAC:C	donor_loss	1.0000
12:110724657:TA:T	donor_loss	1.0000
12:110724658:A:AC	donor_gain	1.0000
12:110724658:A:AT	donor_loss	1.0000
12:110724659:C:CC	donor_gain	1.0000
12:110724659:CCT:C	donor_gain	1.0000
12:110724761:TTAC:T	acceptor_gain	1.0000
12:110724762:TAC:T	acceptor_gain	1.0000
12:110724764:CCTG:C	acceptor_loss	1.0000
12:110724765:C:CC	acceptor_gain	1.0000
12:110724771:T:C	acceptor_gain	1.0000
12:110724771:T:TC	acceptor_gain	1.0000
12:110730523:ACTT:A	donor_loss	1.0000
12:110730525:TT:T	donor_loss	1.0000
12:110730526:T:TG	donor_loss	1.0000
12:110730527:A:AC	donor_gain	1.0000
12:110730527:ACATT:A	donor_gain	1.0000
12:110730528:C:CT	donor_gain	1.0000
12:110730528:C:G	donor_loss	1.0000
12:110730528:CA:C	donor_gain	1.0000

AlphaMissense

2139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:110722138:A:C	F293L	1.000
12:110722138:A:T	F293L	1.000
12:110722139:A:G	F293S	1.000
12:110722140:A:G	F293L	1.000
12:110722175:G:T	A281D	1.000
12:110722176:C:G	A281P	1.000
12:110722178:C:A	G280V	1.000
12:110722178:C:T	G280D	1.000
12:110722179:C:G	G280R	1.000
12:110722183:A:C	N278K	1.000
12:110722183:A:T	N278K	1.000
12:110722189:A:C	F276L	1.000
12:110722189:A:T	F276L	1.000
12:110722190:A:G	F276S	1.000
12:110722191:A:G	F276L	1.000
12:110722191:A:T	F276I	1.000
12:110722198:G:C	C273W	1.000
12:110722202:T:C	Y272C	1.000
12:110722203:A:G	Y272H	1.000
12:110722208:G:T	P270H	1.000
12:110722211:G:T	A269E	1.000
12:110722214:G:A	S268F	1.000
12:110722215:A:G	S268P	1.000
12:110722216:A:C	F267L	1.000
12:110722216:A:T	F267L	1.000
12:110722217:A:C	F267C	1.000
12:110722217:A:G	F267S	1.000
12:110722218:A:C	F267V	1.000
12:110722218:A:G	F267L	1.000
12:110722218:A:T	F267I	1.000

dbSNP variants (sampled 300 via entrez): RS1000006111 (12:110707912 T>A,C), RS1000128354 (12:110712088 C>A,T), RS1000241353 (12:110709532 A>T), RS1000301718 (12:110724096 A>C), RS1000411725 (12:110729686 A>G), RS1000638306 (12:110716311 G>A), RS1000684657 (12:110722797 G>A), RS1000684729 (12:110742087 C>G,T), RS1000789809 (12:110736237 G>C,T), RS1000904819 (12:110716532 C>T), RS1000923121 (12:110734343 T>C), RS1001016018 (12:110713496 A>T), RS1001037237 (12:110734007 C>T), RS1001267973 (12:110719218 G>A), RS1001277069 (12:110711786 G>A)

Disease associations

OMIM: gene MIM:176914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001969_23	Heart rate	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4438 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,679 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL48449	CANTHARIDIN	4	4,679

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

43 potent at pChembl≥5 of 44 total, top 41 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	MICROCYSTIN-LR
10.70	IC50	0.02	nM	MICROCYSTIN-LR
9.85	IC50	0.14	nM	CALYCULIN A
9.40	IC50	0.4	nM	CALYCULIN A
9.35	IC50	0.45	nM	CALYCULIN A
9.25	IC50	0.56	nM	MICROCYSTIN-LR
9.10	IC50	0.8	nM	MICROCYSTIN-LR
8.80	IC50	1.6	nM	CHEMBL1366322
8.72	IC50	1.9	nM	MICROCYSTIN-LR
8.66	IC50	2.2	nM	CALYCULIN A
8.47	Ki	3.4	nM	CHEMBL408120
8.35	Ki	4.5	nM	TAUTOMYCIN DIACID
8.10	Ki	8	nM	CHEMBL405248
8.08	Ki	8.4	nM	CHEMBL261577
7.76	Ki	17.3	nM	CHEMBL427915
7.71	Ki	19.6	nM	CHEMBL406283
7.70	IC50	20	nM	OKADAIC ACID
7.67	Ki	21.3	nM	CHEMBL259235
7.62	Ki	23.9	nM	CHEMBL436904
7.55	IC50	28	nM	OKADAIC ACID
7.54	IC50	29	nM	MICROCYSTIN-LR
7.49	Ki	32.5	nM	CHEMBL261094
7.46	IC50	35	nM	MICROCYSTIN-LR
7.35	IC50	45	nM	OKADAIC ACID
7.32	IC50	48	nM	CALYCULIN A
7.32	IC50	48	nM	OKADAIC ACID
7.30	Ki	49.7	nM	CHEMBL261583
7.24	IC50	58	nM	CALYCULIN A
7.11	IC50	78	nM	OKADAIC ACID
6.70	IC50	200	nM	MICROCYSTIN-LR
6.66	IC50	220	nM	CHEMBL200117
6.58	IC50	260	nM	OKADAIC ACID
5.94	IC50	1150	nM	OKADAIC ACID
5.89	IC50	1300	nM	CHEMBL202197
5.75	IC50	1780	nM	CANTHARIDIN
5.70	IC50	1980	nM	DEMETHYL-CANTHARIDIN
5.54	Kd	2883	nM	CHEMBL5653589
5.53	IC50	2960	nM	CHEMBL16701
5.52	ED50	3047	nM	CHEMBL5653589
5.33	IC50	4710	nM	CHEMBL278014
5.32	IC50	4820	nM	CHEMBL17154

PubChem BioAssay actives

40 with measured affinity, of 62 total; 20 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(5R,8S,11R,12S,15S,18S,19S,22R)-15-[3-(diaminomethylideneamino)propyl]-18-[(1E,3E,5S,6S)-6-methoxy-3,5-dimethyl-7-phenylhepta-1,3-dienyl]-1,5,12,19-tetramethyl-2-methylidene-8-(2-methylpropyl)-3,6,9,13,16,20,25-heptaoxo-1,4,7,10,14,17,21-heptazacyclopentacosane-11,22-dicarboxylic acid	200713: Inhibition of Serine/threonine protein phosphatase 1 (PP1) mutants by natural toxins in D220V	ic50	<0.0001	uM
[(2R,3R,5R,7R,8S,9S)-2-[(1S,3S,4S,5R,6R,7E,9E,11E,13Z)-14-cyano-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyltetradeca-7,9,11,13-tetraenyl]-9-[(E)-3-[2-[(2S)-4-[[(2S,3S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoyl]amino]butan-2-yl]-1,3-oxazol-4-yl]prop-2-enyl]-7-hydroxy-4,4,8-trimethyl-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate	200713: Inhibition of Serine/threonine protein phosphatase 1 (PP1) mutants by natural toxins in D220V	ic50	0.0001	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4E)-4-[2-[3-[(3-azido-4-fluorobenzoyl)amino]propylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0034	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0045	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4E)-4-[2-(3-benzoylanilino)-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0080	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4Z)-4-[2-[2-[(3-azido-4-fluorobenzoyl)amino]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0084	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4E)-4-[2-[2-[(3-azido-4-fluorobenzoyl)amino]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0173	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4E)-4-[2-[2-[2-[(3-azido-4-fluorobenzoyl)amino]ethyldisulfanyl]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0196	uM
(2R)-3-[(2S,6R,8S,11R)-2-[(E,2R)-4-[(2S,2’R,4R,4aS,6R,8aR)-4-hydroxy-2-[(1S,3S)-1-hydroxy-3-[(2S,3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl]butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5’-oxolane]-2’-yl]but-3-en-2-yl]-11-hydroxy-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-hydroxy-2-methylpropanoic acid	200723: Inhibitory activity against serine/threonine protein phosphatase 1(PP1)	ic50	0.0200	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-5,9-dihydroxy-4-methoxy-12-[(2S,3S,6R,8S,9R)-8-[(3S,4E)-4-[2-[2-[[2-methoxy-4-[3-(trifluoromethyl)diazirin-3-yl]benzoyl]amino]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0213	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4Z)-4-[2-[2-[2-[(3-azido-4-fluorobenzoyl)amino]ethyldisulfanyl]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0239	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-8-[(3S,4Z)-4-[2-(3-benzoylanilino)-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0325	uM
(Z)-2-[(1R)-3-[(3R,4S,5R,8S,9S,12R)-5,9-dihydroxy-4-methoxy-12-[(2S,3S,6R,8S,9R)-8-[(3S,4Z)-4-[2-[2-[[2-methoxy-4-[3-(trifluoromethyl)diazirin-3-yl]benzoyl]amino]ethylamino]-2-oxoethoxy]imino-3-methylpentyl]-3,9-dimethyl-1,7-dioxaspiro[5.5]undecan-2-yl]-2,8-dimethyl-7-oxotridecan-3-yl]oxy-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid	325162: Inhibition of PP1gamma by firefly bioluminescence assay	ki	0.0497	uM
2-[4-[7-(4-tetradecylbenzoyl)cyclopenta[d]oxazin-4-yl]phenoxy]acetic acid	259928: Inhibitory activity against Protein phosphatase 1	ic50	0.2200	uM
2-[4-[7-[4-(aminomethyl)benzoyl]cyclopenta[d]oxazin-4-yl]phenoxy]acetic acid	259928: Inhibitory activity against Protein phosphatase 1	ic50	1.3000	uM
Cantharidin	200722: Inhibition of Serine/threonine protein phosphatase 1 by anhydride modified Cantharidin analogues	ic50	1.7800	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149049: Binding affinity to human PPP1CC incubated for 45 mins by Kinobead based pull down assay	kd	2.8828	uM
(4R)-3-ethoxycarbonyl-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid	200722: Inhibition of Serine/threonine protein phosphatase 1 by anhydride modified Cantharidin analogues	ic50	2.9600	uM
(4R)-3-methoxycarbonyl-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid	200722: Inhibition of Serine/threonine protein phosphatase 1 by anhydride modified Cantharidin analogues	ic50	4.7100	uM
(4R)-3-propoxycarbonyl-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid	200722: Inhibition of Serine/threonine protein phosphatase 1 by anhydride modified Cantharidin analogues	ic50	4.8200	uM

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, increases reaction, decreases methylation	2
sodium arsenite	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
U 0126	affects expression, affects reaction	1
calfactant	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Antimycin A	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dimethyl Sulfoxide	increases expression	1
Fluorouracil	affects reaction, decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	increases expression, affects cotreatment	1

ChEMBL screening assays

34 unique, capped per target: 34 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3721026	Binding	Inhibition of recombinant PP1C gamma1-isoform (unknown origin) pre-incubated for 15 mins with enzyme before 32P-labeled MBP substrate addition	Tautomycetin and Tautomycetin analog biosynthesis

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2BS	Abcam HeLa PPP1CC KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.