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Protein / target

Protein phosphatase 3 catalytic subunit alpha

Encoded byPPP3CAQ08209Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
18
Clinical trials
Small-molecule tractable
Druggability
Druggable Family

Protein at a glance

Biological role

Calmodulin-dependent protein phosphatase

Strongest disease association

early-infantile DEE

Via encoding gene PPP3CA · Genetic literature evidence · score 0.76

Therapeutic position

Established drug target

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals.

View complete UniProt function annotation

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679)

Subcellular location

CytoplasmCell membraneCell membrane, sarcolemmaCytoplasm, myofibril, sarcomere, Z lineCell projection, dendritic spine
Domains and Gene Ontology detail (53)

Gene Ontology

  • Ccalcineurin complex
  • Ccytoplasm
  • Ccytosol
  • Cdendritic spine
  • Cextrinsic component of plasma membrane
  • Cglutamatergic synapse
  • Cmitochondrion
  • Cnucleoplasm
  • Cplasma membrane
  • Csarcolemma
  • CSchaffer collateral - CA1 synapse
  • CZ disc

521 aa · 59 kDa · 5 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOCell proliferation & survivalGOCell migrationGOTranscriptional regulationUniProt · GOImmune signallingUniProt · GO
View supporting evidence

Synaptic signalling

  • ·glutamatergic synapse
  • ·Schaffer collateral - CA1 synapse
  • ·modulation of chemical synaptic transmission
  • ·postsynaptic modulation of chemical synaptic transmission

Cell proliferation & survival

  • ·regulation of cell proliferation involved in kidney morphogenesis

Cell migration

  • ·positive regulation of cell migration

Transcriptional regulation

  • ·Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential ro…
  • ·negative regulation of gene expression
  • ·positive regulation of gene expression
  • ·positive regulation of transcription by RNA polymerase II

Immune signalling

  • ·Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential ro…
  • ·positive regulation of activated T cell proliferation
  • ·T cell activation

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Immune System Diseases1 medicine
Lupus Nephritis1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

voclosporin
Narrow target profileApprovedInhibitor

Serine/threonine protein phosphatase 2B catalytic subunit, alpha isoform inhibitor

Indicated for Immune System Diseases, Lupus Nephritis

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PPP3CA

Gene-level evidence surfaced through the gene PPP3CAthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn
0.74Moderately supported

Genetic evidence dominant · Open Targets 0.45

Diabetes Mellitus, Type 2
0.73Moderately supported

Genetic evidence dominant · Open Targets 0.45

Obesity disorder
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.38

early-infantile DEE
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.46

Genetic developmental and epileptic encephalopathy
0.49Limited support

Genetic literature evidence dominant · Open Targets 0.37

View evidence synthesis (5)
Genetic Diseases, InbornModerately supported
0.74
agreement 0.620.86
Genetic100%

Open Targets aggregate 0.45 · 1 independent evidence family

Diabetes Mellitus, Type 2Moderately supported
0.73
agreement 0.590.87
Genetic94%Literature6%

Open Targets aggregate 0.45 · 2 independent evidence families

Obesity disorderModerately supported
0.62
agreement 0.480.76
Genetic99%Literature1%

Open Targets aggregate 0.38 · 2 independent evidence families

early-infantile DEEModerately supported
0.61
agreement 0.450.76
Genetic literature100%

Open Targets aggregate 0.46 · 1 independent evidence family

Genetic developmental and epileptic encephalopathyLimited support
0.49
agreement 0.340.65
Genetic literature97%Literature3%

Open Targets aggregate 0.37 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
early-infantile DEE0.46
Diabetes Mellitus, Type 20.45
Genetic Diseases, Inborn0.45
Obesity disorder0.38
Genetic developmental and epileptic encephalopathy0.37

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)
VOCLOSPORINApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesEmerging

Feasibility evidence (druggable family) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (8)
SM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

18

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (14)

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2022-09-15

    Approval: Lupkynis (EMA)

    ema · regulatory · ema · via voclosporin

  2. New publication2011-09-22
    The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation.

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011 · 64 citations · Europe PMC · via voclosporin

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.