Details for: PPP2R2C

Gene ID: 5522

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PPP2R2C

Ensembl ID: ENSG00000074211

Description: protein phosphatase 2 regulatory subunit Bgamma

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 29.55
    rCSI 38.1%
    PRS 97.08
  • sncg GABAergic cortical interneuron CL4023015
    CSI 24.23
    rCSI 38.97%
    PRS 96.49
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 23.45
    rCSI 29.17%
    PRS 96.2
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 22.34
    rCSI 48.46%
    PRS 94.6
  • VIP GABAergic cortical interneuron CL4023016
    CSI 22.06
    rCSI 26.35%
    PRS 96.55
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 21.43
    rCSI 37.84%
    PRS 96.66
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 21.24
    rCSI 35.64%
    PRS 96.97
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 20.55
    rCSI 49.94%
    PRS 95.61
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 20.01
    rCSI 47.86%
    PRS 95.45
  • ependymal cell CL0000065
    CSI 17.43
    rCSI 35.36%
    PRS 94.25
  • L6b glutamatergic cortical neuron CL4023038
    CSI 16.7
    rCSI 52.2%
    PRS 96.65
  • retinal ganglion cell CL0000740
    CSI 16.26
    rCSI 35.92%
    PRS 96.59
  • cerebral cortex endothelial cell CL1001602
    CSI 16.18
    rCSI 27.98%
    PRS 97.81
  • inhibitory interneuron CL0000498
    CSI 15.78
    rCSI 36.42%
    PRS 96.69
  • neural cell CL0002319
    CSI 15.59
    rCSI 58.82%
    PRS 94.48
  • glutamatergic neuron CL0000679
    CSI 15.3
    rCSI 31.45%
    PRS 94.63
  • retinal bipolar neuron CL0000748
    CSI 15.04
    rCSI 28.17%
    PRS 97.01
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 14.82
    rCSI 53.33%
    PRS 95.99
  • neuron CL0000540
    CSI 13.76
    rCSI 36.65%
    PRS 94.39
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 13.55
    rCSI 51.2%
    PRS 96.09
  • cerebellar granule cell CL0001031
    CSI 12.94
    rCSI 19.02%
    PRS 97.23
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 12.51
    rCSI 41.12%
    PRS 94.99
  • basal cell CL0000646
    CSI 12.33
    rCSI 16.49%
    PRS 98.59
  • rod bipolar cell CL0000751
    CSI 12.04
    rCSI 21.63%
    PRS 97.58
  • amacrine cell CL0000561
    CSI 11.04
    rCSI 31.99%
    PRS 96.68
  • cerebral cortex neuron CL0010012
    CSI 10.67
    rCSI 43.47%
    PRS 96.33
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 9.72
    rCSI 30.41%
    PRS 97.01
  • interneuron CL0000099
    CSI 9.28
    rCSI 18.63%
    PRS 97.87
  • astrocyte of the cerebral cortex CL0002605
    CSI 9.23
    rCSI 20.69%
    PRS 96.77
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.44
    rCSI 49.68%
    PRS 96.18
  • glial cell CL0000125
    CSI 7.95
    rCSI 30.27%
    PRS 96.9
  • central nervous system neuron CL2000029
    CSI 7.22
    rCSI 53.04%
    PRS 96.98
  • glycinergic amacrine cell CL4030028
    CSI 7.18
    rCSI 18.7%
    PRS 96.32
  • vascular leptomeningeal cell CL4023051
    CSI 7.1
    rCSI 12.45%
    PRS 97.9
  • serotonergic neuron CL0000850
    CSI 6.92
    rCSI 30.91%
    PRS 93.56
  • neural progenitor cell CL0011020
    CSI 6.9
    rCSI 30.38%
    PRS 94.91
  • GABAergic neuron CL0000617
    CSI 6.48
    rCSI 21.72%
    PRS 94.4
  • medium spiny neuron CL1001474
    CSI 6.28
    rCSI 54.11%
    PRS 96.45
  • dopaminergic neuron CL0000700
    CSI 6.13
    rCSI 34.63%
    PRS 95.76
  • conjunctival epithelial cell CL1000432
    CSI 4.43
    rCSI 6.77%
    PRS 98.69
  • ON parasol ganglion cell CL4033052
    CSI 3.78
    rCSI 53.64%
    PRS 95.95
  • corneal epithelial cell CL0000575
    CSI 2.98
    rCSI 8.51%
    PRS 98.9
  • ON midget ganglion cell CL4033046
    CSI 2.63
    rCSI 53.58%
    PRS 96.16
  • OFF midget ganglion cell CL4033047
    CSI 2.6
    rCSI 53.01%
    PRS 96.09
  • macroglial cell CL0000126
    CSI 2.56
    rCSI 6.57%
    PRS 97.58
  • direct pathway medium spiny neuron CL4023026
    CSI 2.33
    rCSI 55.82%
    PRS 94.97
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.31
    rCSI 55.63%
    PRS 94.75
  • Cajal-Retzius cell CL0000695
    CSI 1.69
    rCSI 13.21%
    PRS 98.75
  • GABAergic amacrine cell CL4030027
    CSI 1.49
    rCSI 5.11%
    PRS 94.65
  • cerebellar neuron CL1001611
    CSI 1.35
    rCSI 11.88%
    PRS 94.69

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary **[PPP2R2C](/details-gene/5522)**, or Protein Phosphatase 2 Regulatory Subunit Bgamma, is a protein-coding gene located on chromosome 4p16.1. It encodes a regulatory B subunit of the highly conserved serine/threonine-protein phosphatase 2A (PP2A) holoenzyme. Functionally, [PPP2R2C](/details-gene/5522) is critical for modulating the activity and substrate specificity of the PP2A complex, a key regulator of numerous cellular signaling pathways. Expression data reveals that [PPP2R2C](/details-gene/5522) is predominantly and abundantly expressed in the central nervous system, showing particularly high significance in a diverse array of neuronal subtypes. This includes various GABAergic interneurons, such as [sst GABAergic cortical interneuron](/details-cell/CL4023017) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), as well as multiple classes of glutamatergic neurons, like the [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059), highlighting its fundamental role in cortical circuitry and neuronal function. ## Cellular Roles and Expression Landscape The expression profile of **[PPP2R2C](/details-gene/5522)** underscores its specialized role within the central nervous system. **Overall**, the gene exhibits its highest significance scores in a wide range of neuronal populations, establishing it as a key component of the neural molecular machinery. The most significant expression is observed in distinct classes of cortical neurons. It is a defining marker for multiple types of inhibitory interneurons, including [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 29.55), [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 24.23), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 23.45), and [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 22.06). Concurrently, it is highly expressed in excitatory glutamatergic neurons across different cortical layers, such as [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059) (CSI: 22.34) and [L4 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030063) (CSI: 20.01). This broad yet specific expression pattern across both inhibitory and excitatory neuronal systems suggests that [PPP2R2C](/details-gene/5522) is involved in fundamental processes common to most neurons, likely related to the regulation of signaling cascades that maintain neuronal homeostasis and function. Beyond cortical neurons, significant expression is also noted in other neural and related cell types, including [ependymal cell](/details-cell/CL0000065), [retinal ganglion cell](/details-cell/CL0000740), and [cerebral cortex endothelial cell](/details-cell/CL1001602). This indicates a broader, yet still CNS-centric, role for the gene. The consistent high expression in diverse [neural cell](/details-cell/CL0002319) populations strongly suggests that [PPP2R2C](/details-gene/5522) is not merely a marker of a specific neuronal lineage but rather a crucial functional component for a wide spectrum of mature neurons. ## Pathways and Molecular Function Functionally, **[PPP2R2C](/details-gene/5522)** operates as a protein phosphatase regulator ([GO:0019888](https://www.ebi.ac.uk/QuickGO/term/GO:0019888)) within the [cytosol](/details-cell/GO:0005829). It forms a part of the [protein phosphatase type 2A complex](/details-cell/GO:0000159), where its role is to direct the catalytic subunit to specific substrates, thereby conferring specificity to the dephosphorylation event. The PP2A enzyme is a master regulator of phosphorylation-dependent signaling, and its activity is tightly controlled by a diverse family of regulatory B subunits. The brain-abundant expression of [PPP2R2C](/details-gene/5522) was established in early cloning and mapping studies ([Link](https://pubmed.ncbi.nlm.nih.gov/10945473/)), and its high expression in various neuronal subtypes is consistent with a critical role in neuro-specific signaling pathways. These could include pathways governing synaptic plasticity, dendritic arborization, axonal transport, and neuronal survival, all of which are heavily regulated by reversible protein phosphorylation. For instance, [PPP2R2C](/details-gene/5522) has been shown to be involved in modulating the transcriptional activity of Heat Shock Factor 1 (HSF1), a key player in the cellular stress response, through its interaction with the PP2A complex ([Link](https://pubmed.ncbi.nlm.nih.gov/25816751/)). This suggests one mechanism by which [PPP2R2C](/details-gene/5522) may contribute to neuronal health and resilience. ## Research Directions The highly specific and abundant expression of **[PPP2R2C](/details-gene/5522)** within diverse neuronal populations positions it as a critical regulator of CNS function, yet its precise substrates and pathways remain largely uncharacterized. Future research should focus on elucidating its specific roles in different neuronal contexts. **Proposed Hypotheses:** 1. Given its high expression across functionally distinct neuronal types (e.g., inhibitory [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) and excitatory [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059)), it is hypothesized that the **[PPP2R2C](/details-gene/5522)**-containing PP2A holoenzyme dephosphorylates distinct sets of substrates in different neuronal subtypes, thereby fine-tuning neuron-class-specific processes such as neurotransmitter release machinery or postsynaptic receptor trafficking. 2. The stable, high expression in mature neurons suggests a crucial role in maintaining neuronal homeostasis. It is hypothesized that loss-of-function mutations or dysregulation of **[PPP2R2C](/details-gene/5522)** could disrupt the phosphoprotein balance, leading to synaptic dysfunction and potentially contributing to the pathology of neurodegenerative diseases characterized by aberrant protein phosphorylation, such as Alzheimer's disease. **Experimental Approach:** To test the first hypothesis regarding substrate specificity, a powerful approach would be to use in vivo proximity-dependent biotinylation (BioID). A mouse model could be generated where a Cre-recombinase-dependent construct expressing a BioID-tagged **[PPP2R2C](/details-gene/5522)** is targeted to specific neuronal populations by crossing with driver lines (e.g., Pvalb-Cre or Sst-Cre). Biotinylated proteins, representing the proximal interactome and potential substrates of the **[PPP2R2C](/details-gene/5522)**-PP2A complex, could then be isolated from the relevant cortical regions and identified by mass spectrometry. Comparing the substrate profiles between different neuronal subtypes would directly reveal its context-dependent regulatory roles. **Therapeutic Potential:** As a regulatory subunit of a major phosphatase, **[PPP2R2C](/details-gene/5522)** represents a potentially high-impact therapeutic target for neurological disorders. However, it is also challenging. Its broad expression across many essential neuron types means that systemic inhibition could lead to significant on-target neurotoxicity. A more viable strategy might involve developing small molecules that selectively modulate the interaction of **[PPP2R2C](/details-gene/5522)** with a specific disease-relevant substrate, rather than inhibiting the entire complex. If its loss of function is implicated in a disease, therapies aimed at stabilizing the **[PPP2R2C](/details-gene/5522)**-containing PP2A holoenzyme could be beneficial. Therefore, therapeutic intervention would likely require a deep understanding of its specific pathogenic mechanism and the development of highly selective modulators.

Genular Protein ID: 2451582647

Symbol: 2ABG_HUMAN

Name: Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform

UniProtKB Accession Codes:

Q9Y2T4 A8MSY7 B7Z3Y1 Q7Z4V7 Q8NEC4 Q9H3G7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 5 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 5 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10574460

Title: Genomic structure and localization of the human phosphatase 2A BR gamma regulatory subunit.

PubMed ID: 10574460

DOI: 10.1093/dnares/6.5.323

PubMed ID: 10945473

Title: Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16.

PubMed ID: 10945473

DOI: 10.1006/geno.2000.6219

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 25816751

Title: HSF1 transcriptional activity is modulated by IER5 and PP2A/B55.

PubMed ID: 25816751

DOI: 10.1016/j.febslet.2015.03.019

Sequence Information:

  • Length: 447
  • Mass: 51515
  • Checksum: DB002C2384686BBD
  • Sequence:
    • MGEDTDTRKI NHSFLRDHSY VTEADIISTV EFNHTGELLA TGDKGGRVVI FQREPESKNA 
PHSQGEYDVY STFQSHEPEF DYLKSLEIEE KINKIKWLPQ QNAAHSLLST NDKTIKLWKI 
TERDKRPEGY NLKDEEGKLK DLSTVTSLQV PVLKPMDLMV EVSPRRIFAN GHTYHINSIS 
VNSDCETYMS ADDLRINLWH LAITDRSFNI VDIKPANMED LTEVITASEF HPHHCNLFVY 
SSSKGSLRLC DMRAAALCDK HSKLFEEPED PSNRSFFSEI ISSVSDVKFS HSGRYMLTRD 
YLTVKVWDLN MEARPIETYQ VHDYLRSKLC SLYENDCIFD KFECAWNGSD SVIMTGAYNN 
FFRMFDRNTK RDVTLEASRE SSKPRAVLKP RRVCVGGKRR RDDISVDSLD FTKKILHTAW 
HPAENIIAIA ATNNLYIFQD KVNSDMH