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PsychedeliaDokholyan Laboratory
TargetEnzymes

Protein phosphatase 3 catalytic subunit alpha

Named enzymes, including the metabolising cytochromes and the monoamine oxidases.

Measurements
14
Compounds
7
Binding constants
7
Median pX
—

I · Identity

What this target is

Its function as UniProt states it, where in a cell the protein is found, and which cell types and tissues transcribe its gene.

Protein

PP2BA_HUMANPPP3CAHomo sapiens

Protein phosphatase 3 catalytic subunit alpha

Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals15671020,18838687,19154138,23468591,30254215. Many of the substrates contain a PxIxIT motif and/or a LxVP motif17498738,17502104,22343722,23468591,27974827. In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation15671020. In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion18838687. 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 NFATC119154138. In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation26248042. Dephosphorylates and inactivates transcription factor ELK119154138. Dephosphorylates DARPP3219154138. May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins30611118. Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation33691586. 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 WNK430718414. Negatively regulates SLC9A1 activity31375679

Quoted from UniProt’s FUNCTION annotation for Q08209 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

PartnerCombinedExperimentDatabaseText mining
NFATC10.9990.9760.9000.850
PPP3R10.9990.9970.9000.998
CALM30.9990.9270.9000.983
CALML40.9970.1470.9000.970
CALML30.9970.1780.9000.971
CALML60.9970.1470.9000.969
CALML50.9970.1780.9000.971
RCAN10.9970.9900.0000.760
PPP3CB0.9940.6160.9000.868
PPP3R20.9930.7920.9000.685

Where it sits in the cell

  • Cytosol
  • Nucleoplasmadditional
  • Calyxadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm · Cell membrane · Cell membrane, sarcolemma · Cytoplasm, myofibril, sarcomere, Z line · Cell projection, dendritic spine

Expression by cell type

Single cell type RNA, the 4 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Prostatic glandular cells2,545.2 nCPM
  • Neutrophils2,460.1 nCPM
  • Brain inhibitory neurons1,380.6 nCPM
  • Brain excitatory neurons1,219.9 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

  • brain144.7 nTPM

II · Anatomy

Where the gene is transcribed

The same two atlases the compound plates use, asked about this gene alone. Brain on the left, peripheral and autonomic tissues on the right.

Brain

cerebral cortex — 114.2 nTPM, from PPP3CAcerebellum — 94.9 nTPM, from PPP3CAhippocampal formation — 83.8 nTPM, from PPP3CAamygdala — 47.7 nTPM, from PPP3CAhypothalamus — 29.5 nTPM, from PPP3CAthalamus — no resolved target expressed herebasal ganglia — 144.7 nTPM, from PPP3CAmedulla oblongata — no resolved target expressed here

basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.

Measured but not drawn — this anatomogram has no outline for them: retina 25.6, midbrain 18.5, spinal cord 14.7, pituitary gland 8.1.

Body

heart — 8.6 nTPM, from PPP3CAsmooth muscle — 14.5 nTPM, from PPP3CAlung — 18.8 nTPM, from PPP3CAliver — 15.9 nTPM, from PPP3CAkidney — 10.4 nTPM, from PPP3CAstomach — 21.1 nTPM, from PPP3CAduodenum — 10.9 nTPM, from PPP3CAsmall intestine — 12.1 nTPM, from PPP3CAcolon — 18.2 nTPM, from PPP3CAadrenal gland — 16.5 nTPM, from PPP3CAthyroid gland — 12.4 nTPM, from PPP3CApancreas — 8.9 nTPM, from PPP3CAurinary bladder — 19.4 nTPM, from PPP3CAskeletal muscle — 47.9 nTPM, from PPP3CAspleen — 13.7 nTPM, from PPP3CAsalivary gland — 20.9 nTPM, from PPP3CA
0145 nTPM

Square-root ramp · shared scale across both plates

Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of PPP3CA transcript above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.

Brain · 10

  • basal ganglia144.7 nTPM
  • cerebral cortex114.2 nTPM
  • cerebellum94.9 nTPM
  • hippocampal formation83.8 nTPM
  • amygdala47.7 nTPM
  • hypothalamus29.5 nTPM
  • retina25.6 nTPM
  • midbrain18.5 nTPM
  • spinal cord14.7 nTPM
  • pituitary gland8.1 nTPM

Peripheral and autonomic · 16

  • skeletal muscle47.9 nTPM
  • stomach 121.1 nTPM
  • salivary gland20.9 nTPM
  • urinary bladder19.4 nTPM
  • lung18.8 nTPM
  • colon18.2 nTPM
  • adrenal gland16.5 nTPM
  • liver15.9 nTPM
  • smooth muscle14.5 nTPM
  • spleen13.7 nTPM
  • thyroid gland12.4 nTPM
  • small intestine12.1 nTPM
  • duodenum10.9 nTPM
  • kidney10.4 nTPM
  • pancreas8.9 nTPM
  • heart muscle8.6 nTPM

Transcript is not protein. These are RNA levels for PPP3CA, shaded on √nTPM so that a three-order range stays legible — on a linear ramp every region but the strongest would read as blank, which looks like absence rather than less. A region carrying no shading is one the atlas reports no consensus value for, not one where the gene is silent. And a gene being transcribed somewhere is not evidence that any compound reaches it. Human Protein Atlas, RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset.

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Equilibrium binding constants 7

Ki and Kd — a concentration at equilibrium. Directly comparable across rows at the same target.

TargetClassTypeValue (nM)pXOrganismAssay
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202

Functional readouts 7

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

TargetClassTypeValue (nM)pXOrganismAssay
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
Protein phosphatase 3 catalytic subunit alphaEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909202
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