PPP1CA

Summary

PPP1CA (protein phosphatase 1 catalytic subunit alpha, HGNC:9281) is a protein-coding gene on chromosome 11q13.2, encoding Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (P62136). Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. It is a selective cancer dependency (DepMap: 64.6% of cell lines).

The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5499 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 64.6% of screened cell lines
• MANE Select transcript: NM_002708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9281
Approved symbol	PPP1CA
Name	protein phosphatase 1 catalytic subunit alpha
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PP1A, PP-1A, PP1alpha
Ensembl gene	ENSG00000172531
Ensembl biotype	protein_coding
OMIM	176875
Entrez	5499

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000312989, ENST00000358239, ENST00000376745, ENST00000526510, ENST00000527663, ENST00000529724, ENST00000532279, ENST00000532446, ENST00000537694, ENST00000542876, ENST00000546202, ENST00000677322, ENST00000677343, ENST00000679175, ENST00000896899, ENST00000896900, ENST00000896901, ENST00000896902, ENST00000896903, ENST00000896904, ENST00000930813, ENST00000930814, ENST00000930816, ENST00000930817, ENST00000930818

RefSeq mRNA: 3 — MANE Select: NM_002708 NM_001008709, NM_002708, NM_206873

CCDS: CCDS31618, CCDS8160, CCDS8161

Canonical transcript exons

ENST00000376745 — 7 exons

Exon	Start	End
ENSE00001471548	67401728	67401858
ENSE00001550236	67398183	67398645
ENSE00003502524	67399561	67399665
ENSE00003512950	67398722	67398856
ENSE00003567007	67400689	67400919
ENSE00003606732	67401068	67401199
ENSE00003660386	67398940	67399163

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.4183 / max 580.1176, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120912	101.8013	1826
120917	4.3783	1199
120910	2.8819	1435
120911	2.0034	1172
120916	0.8764	467
120918	0.4143	226
120913	0.0627	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.53	gold quality
granulocyte	CL:0000094	99.11	gold quality
mucosa of transverse colon	UBERON:0004991	98.68	gold quality
lower esophagus mucosa	UBERON:0035834	98.48	gold quality
monocyte	CL:0000576	98.42	gold quality
leukocyte	CL:0000738	98.41	gold quality
mononuclear cell	CL:0000842	98.36	gold quality
esophagus mucosa	UBERON:0002469	98.01	gold quality
spleen	UBERON:0002106	97.98	gold quality
thymus	UBERON:0002370	97.97	gold quality
apex of heart	UBERON:0002098	97.86	gold quality
blood	UBERON:0000178	97.76	gold quality
lymph node	UBERON:0000029	97.74	gold quality
pharyngeal mucosa	UBERON:0000355	97.66	gold quality
penis	UBERON:0000989	97.40	gold quality
transverse colon	UBERON:0001157	97.38	gold quality
body of stomach	UBERON:0001161	97.36	gold quality
right adrenal gland	UBERON:0001233	97.35	gold quality
oral cavity	UBERON:0000167	97.27	gold quality
right lobe of thyroid gland	UBERON:0001119	97.26	gold quality
vermiform appendix	UBERON:0001154	97.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.22	gold quality
skin of leg	UBERON:0001511	97.21	gold quality
metanephros cortex	UBERON:0010533	97.18	gold quality
right adrenal gland cortex	UBERON:0035827	97.17	gold quality
minor salivary gland	UBERON:0001830	97.16	gold quality
left adrenal gland	UBERON:0001234	97.11	gold quality
skin of abdomen	UBERON:0001416	97.09	gold quality
left lobe of thyroid gland	UBERON:0001120	97.08	gold quality
mouth mucosa	UBERON:0003729	96.99	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	55.68
E-CURD-46	yes	26.44
E-CURD-122	yes	26.15
E-HCAD-1	yes	18.05
E-MTAB-10553	yes	7.22
E-MTAB-10042	yes	6.30
E-CURD-88	yes	4.07
E-GEOD-106540	no	990.81
E-GEOD-81383	no	451.84
E-CURD-120	no	7.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A

miRNA regulators (miRDB)

18 targeting PPP1CA, 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-3686	99.90	70.53	2432
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-558	97.50	67.16	977
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-7976	95.75	65.67	1186
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-874-3P	95.02	65.66	806

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• demonstrated that the dTip60 chromatin-remodeling complex acetylates nucleosomal phospho-H2Av and exchanges it with an unmodified H2Av; both the histone acetyltransferase dTip60 and the atpase Domino/p400 catalyze the exchange of phospho-H2Av (PMID:15528408)
• In Rsf-1 mutant, the levels of histone H3K9 dimethylation and histone H2A variant H2Av were significantly reduced in an euchromatic region juxtaposed with heterochromatin. (PMID:18454204)
• in the absence of H2A.Z, checkpoint-defective telomeres adopt alternative structures, which are permissive for the loading of the capping machinery at Drosophila telomeres. (PMID:18845840)
• PARP1 is targeted to chromatin by association with the histone H2A variant (H2Av). (PMID:21444826)
• H2A.Z nucleosome occupancy has no effect on sequence variability of Drosophila genome (PMID:23472174)
• Unlike other organisms that employ several H2A variants for different functions, the parsimonious fruit fly Drosophila melanogaster gets along with just a single H2A variant, H2A.V. Remarkably, H2A.V unites within one molecule features and functions of two different mammalian H2A variants, H2A.Z and H2A.X. [Review] (PMID:23553272)
• chromatin loosening and associated initiation of gene expression is activated by phosphorylation of H2Av in a nucleosome positioned in promoter regions of PARP-1-dependent genes (PMID:24508391)
• nucleosomes present significant, context-specific barriers to RNAPII in vivo that can be tuned by the incorporation of H2A.Z (PMID:24606920)
• The Drosophila histone variant H2A.V works in concert with HP1 to promote kinetochore-driven microtubule formation. (PMID:25591068)
• The study reports the crystal structure of the H2A.Z-binding domain of Drosophila melanogaster YL1 (dYL1-Z) in complex with an H2A.Z-H2B dimer at 1.9-A resolution. (PMID:26974124)
• The nucleosome positioning sequence (NPS) patterns from H2A.Z nucleosomes differ from the NPS patterns from H2A nucleosomes. The purine-purine/pyrimidine-pyrimidine pattern of H2A.Z nucleosomes has major peaks shifted by 10 bp deviated from the H2A nucleosome pattern. The H2A and H2A.Z nucleosomes have different sequence preferences. (PMID:27992255)
• the H2AZ-like rather than the H2AX-like function of H2AV is primarily required for normal hematopoiesis. (PMID:28242611)
• H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila. (PMID:28807902)
• H2Av continuously exchanges between lipid droplets. (PMID:30044219)
• A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding. (PMID:32115743)
• Drosophila H2Av negatively regulates the activity of the IMD pathway via facilitating Relish SUMOylation. (PMID:34370736)
• Histone variant H2A.Z regulates zygotic genome activation. (PMID:34853314)
• PP1C has a role in binding to PKR protein kinase for its phosphorylation and disruption of dimerization (PMID:12138106)
• PP1C and Inh2 bind to KPI2 to form a regulatory complex that is localized to membranes (PMID:12393858)
• PPICalpha essential in proliferation in HeLa cells (PMID:15492829)
• PP1alpha expression interferes with oncogenic transformation. (PMID:16550609)
• These findings provide a putative mechanism by which transcriptional activity of hnRNP K can be discretely controlled through the regulation of PP1 activity. (PMID:16564677)
• These data suggest that amplification and overexpression of the PP1alpha gene, PPP1CA, may be involved in oral squamous cell carcinoma cell tumorigenesis and/or progression. (PMID:16619035)
• Bcl-2 by competing with IP3R1 for the binding of PP1 can reduce the inositol trisphosphate-mediated calcium signal and protect cells from mitochondrial dysfunction and cell death. (PMID:16874461)
• accumulation of C(16)-ceramide in mitochondria formed from the protein kinase C-dependent salvage pathway results at least in part from the action of longevity-assurance homologue 5, and the generated ceramide modulates the p38 cascade via PP1 (PMID:17030510)
• data indicate that PP1alpha is a downstream target of the NGF/Egr-1/Cdk5 pathway during NGF-induced differentiation of PC12 cells and suggest that PP1 phosphorylation promotes neuronal differentiation (PMID:17202132)
• Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. (PMID:17318175)
• Results suggest that the protein-tyrosine phosphatase domain of tensin exhibits isoform-specific association with PP1alpha in a restricted spatial region of adhesions that are formed during cell migration. (PMID:17435217)
• Sds22 and Inhibitor-3 form a heterotrimeric complex with PP1, both in cell lysates and after purification. A pool of PP1 is complexly controlled by both Sds22 and Inhibitor-3. (PMID:17630778)
• PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. (PMID:18483222)
• Conserved together throughout eukaryotic evolution, I-2, PP1 and Aurora B function interdependently during mitosis. (PMID:18716057)
• The PP1:tautomycin structure is the first complex structure with a toxin with preferred PP1 specificity. (PMID:18992256)
• Protein phosphatase 1 binding occurs through a conserved RVXF motif found in the KH domain of AKAP149. (PMID:19074462)
• novel interaction between the catalytic subunit of protein phosphatase 1alpha and MEF2A. Interaction occurs within the nucleus, and binding of PP1alpha to MEF2 potently represses MEF2-dependent transcription (PMID:19364819)
• AR may function as a PP1 regulatory subunit and mediate PP1a recruitment to chromatin, where it can modulate transcription and splicing. (PMID:19622840)
• Results suggest that PP1alpha bound to tensin1 has effects in reducing migration and invasion that are not mediated through DLC-1, and show the importance of PP1alpha binding to tensin1 for the regulation of cell polarization, migration, and invasion. (PMID:19826001)
• conclusion: protein phosphatase 1alpha associates with the non-catalytic domain of protein tyrosine phosphatase-PEST (PTP-PEST)and regulates PTP activity via dephosphorylation of phospho-Ser39 (PMID:19919952)
• PP-1 ( PP-1alpha or PP-1beta ) acts as a major phosphatase to dephosphorylate AKT1 at Thr-450 and thus modulate its functions in regulating gene expression, cell survival and differentiation. (PMID:20186153)
• 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)
• CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis. (PMID:20663907)

Cross-species orthologs

29 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp1ca	ENSMUSG00000040385
rattus_norvegicus	Ppp1ca	ENSRNOG00000018708
drosophila_melanogaster	Pp1-13C	FBGN0003132
drosophila_melanogaster	Pp1-87B	FBGN0004103
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), PPP1CC (ENSG00000186298), PPP1CB (ENSG00000213639)

Protein

Protein identifiers

Serine/threonine-protein phosphatase PP1-alpha catalytic subunit — P62136 (reviewed: P62136)

All UniProt accessions (4): P62136, A0A140VJS9, A0A7I2V4F7, E9PMD7

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, transcription elongation, 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 Ca(2+)/calmodulin dependent protein kinase II. Catalytic component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation: the PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H. The PNUTS-PP1 complex also regulates transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription. PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at ‘Ser-5’ of the CTD, promoting RNA polymerase II degradation. PNUTS-PP1 also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. 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. Dephosphorylates CENPA. Dephosphorylates the ‘Ser-139’ residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy. Together with PPP1CC (PP1-gamma 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. The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c. (Microbial infection) Necessary for alphaviruses replication.

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 PPP1R39. Interacts with BTBD10. Interacts with KCTD20. Interacts with PPP1R9A and PPP1R9B. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1. Interacts with PPP1R7. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B. Component of the PNUTS-PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on ‘Ser-824’ and forms a complex at the p21 promoter site. Interacts with isoform 1 and isoform 4 of NEK2. Interacts with FER; this promotes phosphorylation at Thr-320. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. Interacts with FOXP3. Interacts with CENPA. Interacts with ATG16L1. Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1. Interacts with tensin TNS1. Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2. Interacts with TPRN; the interaction results in inhibition of PPC1A phosphatase activity. Interacts with SKA1 (via C-terminus); the interaction is direct and required for the recruitment of PP1 to the kinetochore. 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. (Microbial infection) Interacts with HHV-1 ICP34.5. (Microbial infection) Interacts with Venezuelan equine encephalitis virus (VEEV) capsid protein; this interaction dephosphorylates the capsid protein, which increases its ability to bind to the viral genome.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Nucleolus.

Post-translational modifications. Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation.

Activity 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.

Cofactor. Binds 1 Fe cation per subunit. Binds 2 manganese ions per subunit.

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

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

Isoforms (3)

UniProt ID	Names	Canonical?
P62136-1	1	yes
P62136-2	2
P62136-3	3

RefSeq proteins (3): NP_001008709, NP_002699, NP_996756 (=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 (59 total): strand 16, helix 13, binding site 8, modified residue 7, turn 5, mutagenesis site 4, splice variant 2, initiator methionine 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

46 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ZEG	X-RAY DIFFRACTION	1.09
6ZEH	X-RAY DIFFRACTION	1.3
6ZEI	X-RAY DIFFRACTION	1.39
6DNO	X-RAY DIFFRACTION	1.45
4MOV	X-RAY DIFFRACTION	1.45
6OBR	X-RAY DIFFRACTION	1.5
3E7A	X-RAY DIFFRACTION	1.63
3E7B	X-RAY DIFFRACTION	1.7
8SW6	X-RAY DIFFRACTION	1.76
6ZEJ	X-RAY DIFFRACTION	1.78
7T0Y	X-RAY DIFFRACTION	1.8
6OBS	X-RAY DIFFRACTION	1.8
6OBQ	X-RAY DIFFRACTION	1.84
3EGG	X-RAY DIFFRACTION	1.85
6ZEE	X-RAY DIFFRACTION	1.9
6ZK6	X-RAY DIFFRACTION	1.9
6ZEF	X-RAY DIFFRACTION	1.94
6OBU	X-RAY DIFFRACTION	1.95
7TXH	X-RAY DIFFRACTION	1.95
3EGH	X-RAY DIFFRACTION	2
6G0I	X-RAY DIFFRACTION	2
8DWL	X-RAY DIFFRACTION	2
7QFB	X-RAY DIFFRACTION	2.05
3V4Y	X-RAY DIFFRACTION	2.1
6G0J	X-RAY DIFFRACTION	2.1
4MP0	X-RAY DIFFRACTION	2.1
6GHM	X-RAY DIFFRACTION	2.15
7TVF	X-RAY DIFFRACTION	2.17
4MOY	X-RAY DIFFRACTION	2.2
3HVQ	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62136-F1	91.65	0.87

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 (1): 125 (proton donor)

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

Post-translational modifications (7): 2, 2, 22, 305, 306, 320, 325

Mutagenesis-validated functional residues (4):

Position	Phenotype
50	promotes smp complex formation.
57	no effect on smp complex formation.
184	promotes smp complex formation.
188	abolishes smp complex formation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-163560	Triglyceride catabolism
R-HSA-180024	DARPP-32 events
R-HSA-2173788	Downregulation of TGF-beta receptor signaling
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9828806	Maturation of hRSV A proteins
R-HSA-9931530	Phosphorylation and nuclear translocation of the CRY:PER:kinase complex

MSigDB gene sets: 361 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRIGLYCERIDE_CATABOLISM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_CHROMOSOME_ORGANIZATION, GOBP_EPITHELIUM_DEVELOPMENT, MOOTHA_GLYCOGEN_METABOLISM, MORF_MBD4, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_TRANSLATION_IN_RESPONSE_TO_STRESS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_PHOTOPERIODISM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN

GO Biological Process (27): RNA polymerase II promoter clearance (GO:0001111), glycogen metabolic process (GO:0005977), regulation of glycogen catabolic process (GO:0005981), protein dephosphorylation (GO:0006470), response to lead ion (GO:0010288), lung development (GO:0030324), circadian regulation of gene expression (GO:0032922), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), regulation of circadian rhythm (GO:0042752), entrainment of circadian clock by photoperiod (GO:0043153), telomere maintenance in response to DNA damage (GO:0043247), regulation of translational initiation in response to stress (GO:0043558), positive regulation of glycogen biosynthetic process (GO:0045725), branching morphogenesis of an epithelial tube (GO:0048754), protein stabilization (GO:0050821), cell division (GO:0051301), regulation of canonical Wnt signaling pathway (GO:0060828), positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled (GO:2000806), positive regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001241), telomere maintenance (GO:0000723), regulation of glycogen biosynthetic process (GO:0005979), transcription by RNA polymerase II (GO:0006366), transcription elongation by RNA polymerase II (GO:0006368), dephosphorylation (GO:0016311), double-strand break repair via alternative nonhomologous end joining (GO:0097681), cell-cell adhesion (GO:0098609)

GO Molecular Function (13): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), iron ion binding (GO:0005506), protein phosphatase 1 binding (GO:0008157), phosphatase activity (GO:0016791), ribonucleoprotein complex binding (GO:0043021), transition metal ion binding (GO:0046914), cadherin binding involved in cell-cell adhesion (GO:0098641), RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity (GO:0180007), protein binding (GO:0005515), hydrolase activity (GO:0016787), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872)

GO Cellular Component (22): protein phosphatase type 1 complex (GO:0000164), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), glycogen granule (GO:0042587), dendritic spine (GO:0043197), perikaryon (GO:0043204), extracellular exosome (GO:0070062), PTW/PP1 phosphatase complex (GO:0072357), sperm midpiece (GO:0097225), sperm end piece (GO:0097229), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), chromosome, telomeric region (GO:0000781), neuronal cell body (GO:0043025), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Triglyceride metabolism	1
Opioid Signalling	1
TGF-beta receptor signaling activates SMADs	1
mRNA 3’-end processing	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	8
cytoplasm	4
circadian rhythm	2
transcription elongation by RNA polymerase II	2
regulation of transcription elongation by RNA polymerase II	2
binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
intracellular membraneless organelle	2
sperm flagellum	2
synapse	2
promoter clearance during DNA-templated transcription	1
transcription by RNA polymerase II	1
energy reserve metabolic process	1
glucan metabolic process	1
glycogen catabolic process	1
regulation of carbohydrate catabolic process	1
regulation of glycogen metabolic process	1
dephosphorylation	1
protein modification process	1
response to metal ion	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
regulation of gene expression	1
positive regulation of DNA-templated transcription, elongation	1
positive regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
regulation of biological process	1
photoperiodism	1
entrainment of circadian clock	1
telomere maintenance	1
DNA damage response	1
translational initiation	1
regulation of translational initiation	1
cellular response to stress	1
regulation of translation in response to stress	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

666 interactions, top by confidence:

A	B	Type	Score
PPP1CA	PPP1R2	psi-mi:“MI:0407”(direct interaction)	0.950
PPP1CA	PPP1R2	psi-mi:“MI:0915”(physical association)	0.950
CSRNP2	PPP1CA	psi-mi:“MI:0915”(physical association)	0.920
PPP1CA	CSRNP2	psi-mi:“MI:0915”(physical association)	0.920
PPP1CA	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.890
PPP1CA	CSRNP1	psi-mi:“MI:0915”(physical association)	0.870
CSRNP1	PPP1CA	psi-mi:“MI:0915”(physical association)	0.870
PPP1CA	PPP1R7	psi-mi:“MI:0915”(physical association)	0.870
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
PPP1CA	PPP1CC	psi-mi:“MI:0914”(association)	0.850
PPP1CA	PPP1R15A	psi-mi:“MI:0407”(direct interaction)	0.820
PPP1CA	PPP1R15A	psi-mi:“MI:0915”(physical association)	0.820
PPP1CA	PPP1R15A	psi-mi:“MI:0403”(colocalization)	0.820
PPP1R15A	PPP1CA	psi-mi:“MI:0915”(physical association)	0.820
PPP1CA	Ppp1r9b	psi-mi:“MI:0407”(direct interaction)	0.810
PPP1CA	Ppp1r9b	psi-mi:“MI:0915”(physical association)	0.810
RB1	PPP1CA	psi-mi:“MI:0915”(physical association)	0.770
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	PPP1R8	psi-mi:“MI:0407”(direct interaction)	0.690

BioGRID (1260): PPP1CA (Affinity Capture-MS), CSRNP1 (Two-hybrid), CSRNP2 (Two-hybrid), PPP1R2P3 (Two-hybrid), PPP1CA (Affinity Capture-MS), PPP1CA (Affinity Capture-MS), AKT1 (Biochemical Activity), AKT1 (Affinity Capture-Western), PPP1CA (Affinity Capture-Western), PPP1CA (Affinity Capture-MS), PPP1CA (Reconstituted Complex), PPP1CA (Two-hybrid), PPP1CA (Two-hybrid), RORC (Two-hybrid), PPP1CA (Two-hybrid)

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, P30366, P32345, P32598, P32838, P36614, P48463, P48480, P48483, P48528, P48529, P48577

SIGNOR signaling

62 interactions.

A	Effect	B	Mechanism
PPP1CA	down-regulates	MAPK1	dephosphorylation
PPP1CA	down-regulates	MAPK3	dephosphorylation
PPP1CA	down-regulates	AURKA	dephosphorylation
PPP1CA	up-regulates	CDC25C	binding
PPP1CA	up-regulates	CCND3	dephosphorylation
SMAD7	up-regulates	PPP1CA	binding
CDK1	“down-regulates activity”	PPP1CA	phosphorylation
CDK5	“down-regulates activity”	PPP1CA	phosphorylation
PPP1CA	down-regulates	NEK2	dephosphorylation
PPP1R2	down-regulates	PPP1CA	binding
PPP1CA	down-regulates	AKT1	dephosphorylation
PPP1CA	up-regulates	IKZF1	dephosphorylation
PPP1CA	up-regulates	CASP9	dephosphorylation
PPP1CA	up-regulates	PFN1	dephosphorylation
PPP1CA	down-regulates	AKT	dephosphorylation
PPP1CA	“down-regulates activity”	AXIN1	dephosphorylation
PPP1CA	“down-regulates activity”	TP53	dephosphorylation
PPP1CA	“up-regulates activity”	NOS3	dephosphorylation
PPP1CA	“down-regulates activity”	AKT	dephosphorylation
PPP1CA	“down-regulates activity”	BRCA1	dephosphorylation
PPP1CA	“down-regulates activity”	STAT3	dephosphorylation
PPP1CA	“up-regulates activity”	CASP9	dephosphorylation
PPP1CA	“up-regulates quantity by stabilization”	MDM2	dephosphorylation
SHOC2	“up-regulates activity”	PPP1CA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cyclin A:Cdk2-associated events at S phase entry	7	19.6×	2e-05
Cyclin E associated events during G1/S transition	6	18.0×	1e-04
Intrinsic Pathway for Apoptosis	5	15.4×	6e-04
G1/S Transition	6	14.7×	2e-04
Signaling by ALK in cancer	5	14.3×	8e-04
Cyclin D associated events in G1	5	12.3×	1e-03
Mitotic G1 phase and G1/S transition	6	11.6×	5e-04
SCF(Skp2)-mediated degradation of p27/p21	5	10.9×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
glycogen metabolic process	6	23.8×	1e-04
intrinsic apoptotic signaling pathway in response to DNA damage	6	14.6×	1e-03
intrinsic apoptotic signaling pathway	5	13.5×	4e-03
mitotic spindle assembly	5	12.9×	4e-03
centrosome cycle	5	12.7×	4e-03
platelet aggregation	5	12.7×	4e-03
G1/S transition of mitotic cell cycle	8	12.1×	1e-04
neuron apoptotic process	7	9.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3911 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67398643:GAT:G	acceptor_gain	1.0000
11:67398646:C:CC	acceptor_gain	1.0000
11:67398646:CTA:C	acceptor_loss	1.0000
11:67398717:CTCA:C	donor_loss	1.0000
11:67398718:TCA:T	donor_loss	1.0000
11:67398719:CACCT:C	donor_loss	1.0000
11:67398720:A:AC	donor_gain	1.0000
11:67398720:ACCTG:A	donor_loss	1.0000
11:67398721:C:CC	donor_gain	1.0000
11:67398721:C:CT	donor_loss	1.0000
11:67398721:CCT:C	donor_gain	1.0000
11:67398852:ACCAC:A	acceptor_gain	1.0000
11:67398853:CCAC:C	acceptor_gain	1.0000
11:67398853:CCACC:C	acceptor_gain	1.0000
11:67398854:C:CT	acceptor_gain	1.0000
11:67398854:CAC:C	acceptor_gain	1.0000
11:67398855:AC:A	acceptor_gain	1.0000
11:67398856:CC:C	acceptor_gain	1.0000
11:67398857:C:CC	acceptor_gain	1.0000
11:67398857:C:T	acceptor_gain	1.0000
11:67398862:C:CT	acceptor_gain	1.0000
11:67398937:CACC:C	donor_loss	1.0000
11:67398938:ACC:A	donor_loss	1.0000
11:67399159:CAGGC:C	acceptor_gain	1.0000
11:67399160:AGGC:A	acceptor_gain	1.0000
11:67399161:GGC:G	acceptor_gain	1.0000
11:67399164:C:CC	acceptor_gain	1.0000
11:67399164:CTG:C	acceptor_loss	1.0000
11:67399173:C:CT	acceptor_gain	1.0000
11:67399555:CCTCA:C	donor_loss	1.0000

AlphaMissense

2175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67398725:G:C	F293L	1.000
11:67398725:G:T	F293L	1.000
11:67398726:A:G	F293S	1.000
11:67398727:A:G	F293L	1.000
11:67398762:G:T	A281D	1.000
11:67398763:C:G	A281P	1.000
11:67398765:C:T	G280D	1.000
11:67398766:C:G	G280R	1.000
11:67398770:A:C	N278K	1.000
11:67398770:A:T	N278K	1.000
11:67398772:T:C	N278D	1.000
11:67398776:A:C	F276L	1.000
11:67398776:A:T	F276L	1.000
11:67398777:A:G	F276S	1.000
11:67398778:A:G	F276L	1.000
11:67398789:T:C	Y272C	1.000
11:67398790:A:G	Y272H	1.000
11:67398795:G:T	P270H	1.000
11:67398798:G:T	A269D	1.000
11:67398803:G:C	F267L	1.000
11:67398803:G:T	F267L	1.000
11:67398804:A:C	F267C	1.000
11:67398804:A:G	F267S	1.000
11:67398805:A:C	F267V	1.000
11:67398805:A:G	F267L	1.000
11:67398805:A:T	F267I	1.000
11:67398816:A:G	L263P	1.000
11:67398833:G:C	F257L	1.000
11:67398833:G:T	F257L	1.000
11:67398834:A:C	F257C	1.000

dbSNP variants (sampled 300 via entrez): RS1000001898 (11:67401664 C>A,G), RS1000420135 (11:67397913 G>A), RS1000929574 (11:67401620 C>A,G,T), RS1001514580 (11:67401854 G>A), RS1001692033 (11:67403596 G>A,C), RS1001984746 (11:67402021 G>T), RS1002247918 (11:67402240 C>G), RS1002856169 (11:67399387 A>G), RS1003704599 (11:67403352 A>T), RS1003916006 (11:67403725 C>T), RS1003991233 (11:67402628 G>C), RS1004063320 (11:67402309 G>A), RS1005769043 (11:67403395 G>A), RS1005802710 (11:67401237 CAGG>C), RS1006195302 (11:67399450 A>G)

Disease associations

OMIM: gene MIM:176875 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21
GCST008163_537	Height	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2164 (SINGLE PROTEIN), CHEMBL4523747 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523748 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Protein phosphatase catalytic subunits

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
microcystin-LR	Inhibition	10.0	pIC50
calyculin A	Inhibition	9.0	pIC50
okadaic acid	Inhibition	7.22	pIC50
cantharidin	Inhibition	6.8	pIC50

Binding affinities (BindingDB)

43 measured of 53 human assays (60 total across all organisms); most potent 43 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-[(E)-[3-(2-fluoroanilino)-4-keto-1-naphthylidene]amino]sulfonylbenzoic acid	IC50	638 nM
SMR000186252	IC50	707 nM
3-[[(4E)-4-(2,4-dimethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acid	IC50	919 nM
3-[[(4E)-4-(4-ethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acid	IC50	926 nM
(6E)-6-[[[2,6-bis(1-pyrrolidinyl)-4-pyrimidinyl]hydrazo]methylidene]-1-cyclohexa-2,4-dienone	IC50	1030 nM
MLS000686315	IC50	1610 nM
cid_2851959	IC50	1840 nM
cid_367783	IC50	2080 nM
cid_804043	IC50	2320 nM
MLS000768248	IC50	2550 nM
cid_4561725	EC50	2680 nM
N-(2-hydroxy-1,3-dioxoinden-2-yl)-4-(trifluoromethyl)benzamide	IC50	2970 nM
(NZ)-N-[4-keto-3-(1H-1,2,4-triazol-5-ylthio)-1-naphthylidene]-2,4,5-trimethyl-benzenesulfonamide	IC50	3070 nM
N’-(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)-4-methylbenzohydrazide	IC50	5080 nM
cid_2810379	IC50	5130 nM
1-oxidanidyl-2-phenyl-indol-1-ium-3-one	IC50	5800 nM
(4E)-4-[[2-(2,6-dimorpholin-4-ylpyrimidin-4-yl)hydrazinyl]methylidene]-3-hydroxycyclohexa-2,5-dien-1-one	IC50	7150 nM
(2-bromanyl-4,5-dimethoxy-phenyl)-(6,7-dimethoxyisoquinolin-1-yl)methanone	IC50	7370 nM
MLS000720211	IC50	8060 nM
MLS000768249	IC50	8190 nM
MLS000588745	IC50	9720 nM
MLS000585342	IC50	10800 nM
N’-(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)-4-nitrobenzohydrazide	IC50	11900 nM
MLS000085603	IC50	14200 nM
1,8-bis(azanyl)-6-propoxy-3-pyrrolidin-1-yl-2,7-naphthyridine-4-carbonitrile	IC50	15000 nM
CMLD004055	IC50	19000 nM
CMLD003552	IC50	19400 nM
SMR000154351	IC50	20000 nM
MLS000567016	IC50	21200 nM
SMR001223913	IC50	24400 nM
cid_16745758	IC50	28300 nM
5-methyl-4-[(5-methyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)-(4-nitrophenyl)methyl]-2-phenyl-1H-pyrazol-3-one	IC50	29900 nM
SMR000472405	IC50	46900 nM
2-azanyl-N-(2-methoxyethyl)-1-(3-methylbutyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide	IC50	56500 nM
butanedioic acid O4-[3-cyclopropyl-2-(cyclopropylmethyl)-7-methyl-6,8-dioxo-7-isoquinolinyl] ester O1-methyl ester	IC50	63600 nM
SMR000147894	IC50	67000 nM
2-[[(5-methyl-1,3,4-thiadiazol-2-yl)amino]-oxomethyl]-7-oxabicyclo[2.2.1]hept-5-ene-3-carboxylic acid	IC50	67000 nM
SMR000120805	IC50	67000 nM
1,8-bis(azanyl)-3-[butyl(ethyl)amino]-6-ethoxy-2,7-naphthyridine-4-carbonitrile	IC50	67000 nM
MLS000540078	IC50	67000 nM
cid_3159718	IC50	67000 nM
CMLD003523	IC50	67000 nM
cid_664512	IC50	67000 nM

ChEMBL bioactivities

64 potent at pChembl≥5 of 91 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.64	IC50	227.3	nM	CHEMBL1344034
6.57	IC50	271.6	nM	CHEMBL299846
5.71	IC50	1971	nM	CHEMBL1519313
5.63	IC50	2363	nM	CHEMBL1530097
5.61	IC50	2463	nM	CHEMBL1533230
5.61	IC50	2477	nM	CHEMBL1503729
5.57	IC50	2667	nM	CHEMBL567967
5.55	IC50	2846	nM	CHEMBL1329288
5.55	IC50	2832	nM	DEMETHYL-CANTHARIDIN
5.44	IC50	3632	nM	CHEMBL1455825
5.43	IC50	3697	nM	CHEMBL1470871
5.42	IC50	3824	nM	CHEMBL1330307
5.40	IC50	3997	nM	CHEMBL1378339
5.38	IC50	4166	nM	CHEMBL1304402
5.38	IC50	4118	nM	DEMETHYL-CANTHARIDIN
5.34	IC50	4592	nM	CHEMBL1312303
5.33	IC50	4644	nM	CHEMBL1575320
5.32	IC50	4750	nM	CHEMBL1505623
5.30	IC50	4959	nM	CHEMBL1517284
5.30	IC50	4949	nM	CHEMBL1429411
5.29	IC50	5109	nM	CHEMBL1497894
5.29	IC50	5107	nM	CHEMBL1998502
5.28	IC50	5206	nM	CHEMBL1547860
5.25	IC50	5604	nM	CHEMBL1332050
5.24	IC50	5809	nM	CHEMBL3197912
5.24	IC50	5826	nM	CHEMBL1382628
5.24	IC50	5818	nM	CHEMBL1609678
5.23	IC50	5878	nM	CHEMBL1359321
5.22	IC50	5956	nM	CHEMBL1439066
5.22	IC50	6038	nM	CHEMBL1494338
5.22	IC50	5980	nM	CHEMBL1407037
5.21	IC50	6238	nM	CHEMBL1407368
5.20	IC50	6267	nM	CHEMBL1518085
5.20	IC50	6280	nM	CHEMBL1391287
5.19	IC50	6474	nM	CHEMBL1505788
5.19	IC50	6481	nM	CHEMBL1992835
5.18	IC50	6531	nM	CHEMBL1980308
5.18	IC50	6646	nM	CHEMBL1422386
5.18	IC50	6675	nM	CHEMBL3191846
5.18	IC50	6557	nM	CHEMBL1464805
5.18	IC50	6551	nM	CHEMBL490592
5.18	IC50	6656	nM	CHEMBL1510003
5.17	IC50	6758	nM	CHEMBL1334407
5.17	IC50	6797	nM	CHEMBL1433546
5.16	IC50	6859	nM	CHEMBL1501376
5.16	IC50	6947	nM	CHEMBL1471716
5.16	IC50	6958	nM	CHEMBL1353885
5.15	IC50	7028	nM	CHEMBL1594854
5.14	IC50	7215	nM	CHEMBL1537522
5.14	IC50	7268	nM	CHEMBL1562161

PubChem BioAssay actives

1 with measured affinity, of 43 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178749: Inhibition of PPP1CA (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	8.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
moringin	affects cotreatment, increases expression, decreases expression	2
bisphenol A	increases expression, decreases expression	2
sodium arsenite	affects binding, increases reaction, decreases expression	2
cobaltous chloride	decreases expression	2
Aluminum Hydroxide	affects cotreatment, decreases expression, increases reaction, decreases reaction	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
dihydrolipoic acid	decreases expression, decreases reaction, increases reaction, affects cotreatment	1
sodium bichromate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
pyrrolidine dithiocarbamic acid	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
4-hydroxy-2-nonenal	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiloride	decreases phosphorylation, decreases reaction	1
Aminoglutethimide	decreases expression	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613844	Binding	PUBCHEM_BIOASSAY: Counterscreen for inhibitors of PP5: fluorescence-based biochemical high throughput dose response assay for inhibitors of Protein Phosphatase 1 (PP1). (Class of assay: confirmatory) [Related pubchem assays: 2034 (Summary (	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5WT	UM-UC-3 LLWO2F	Cancer cell line	Male
CVCL_C9H0	WAe009-A-B	Embryonic stem cell	Female
CVCL_TF54	HAP1 PPP1CA (-) 1	Cancer cell line	Male
CVCL_TF55	HAP1 PPP1CA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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