Molecule Information

General Information of the Molecule (ID: Mol01905)

• Name: Protein phosphatase 3 catalytic subunit alpha (PPP3CA) ,Homo sapiens
• Synonyms: PPP3R1; CNA2; CNB
• Molecule Type: Protein
• Gene Name: PPP3CA
• Gene ID: 5534
• Location: chr2:68,178,857-68,256,237[-]
• Sequence:
  MGNEASYPLEMCSHFDADEIKRLGKRFKKLDLDNSGSLSVEEFMSLPELQQNPLVQRVID
  IFDTDGNGEVDFKEFIEGVSQFSVKGDKEQKLRFAFRIYDMDKDGYISNGELFQVLKMMV
  GNNLKDTQLQQIVDKTIINADKDGDGRISFEEFCAVVGGLDIHKKMVVDV
• Function: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
• Uniprot ID: CANB1_HUMAN
• Ensembl ID: ENSG00000221823
• HGNC ID: HGNC:9314

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Fenofibrate

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Nonalcoholic fatty liver disease [1]

• Sensitive Disease: Nonalcoholic fatty liver disease [ICD-11: DB92.0]
• Sensitive Drug: Fenofibrate
• Molecule Alteration: Function; Activation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Intracellular calcium flux signaling pathway; Activation; hsa05207
• Cell Pathway Regulation: TFEB/TFE3 nuclear translocation; Activation; hsa04137
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: CaMKKbeta-AMPK signaling pathway; Activation; hsa04152
• In Vivo Model: HFD-fed mouse model; Mus musculus
• Mechanism Description: Administration of fenofibrate effectively ameliorated glucose intolerance and insulin resistance in HFD-fed mice. In this study, fenofibrate treatment appeared to increase intracellular calcium flux and TFEB/TFE3 nuclear translocation and autophagy through two different mechanisms. One is the aforementioned calcium-mediated upregulation of the CaMKKbeta-AMPK pathway and the other is the activation of the calcium-dependent dephosphatase calcineurin subunit PPP3CA.

Disease Class: Insulin-resistance syndrome [1]

• Sensitive Disease: Insulin-resistance syndrome [ICD-11: 5A44.0]
• Sensitive Drug: Fenofibrate
• Molecule Alteration: Function; Activation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Intracellular calcium flux signaling pathway; Activation; hsa05207
• Cell Pathway Regulation: TFEB/TFE3 nuclear translocation; Activation; hsa04137
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: CaMKKbeta-AMPK signaling pathway; Activation; hsa04152
• In Vivo Model: HFD-fed mouse model; Mus musculus
• Mechanism Description: Administration of fenofibrate effectively ameliorated glucose intolerance and insulin resistance in HFD-fed mice. In this study, fenofibrate treatment appeared to increase intracellular calcium flux and TFEB/TFE3 nuclear translocation and autophagy through two different mechanisms. One is the aforementioned calcium-mediated upregulation of the CaMKKbeta-AMPK pathway and the other is the activation of the calcium-dependent dephosphatase calcineurin subunit PPP3CA.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 13

Nonalcoholic fatty liver disease [ICD-11: DB92]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Nonalcoholic fatty liver disease
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.51E-01; Fold-change: 3.81E-01; Z-score: 8.35E-01

References

• Ref 1: Fenofibrate, a PPARAlpha agonist, reduces hepatic fat accumulation through the upregulation of TFEB-mediated lipophagy .Metabolism. 2021 Jul;120:154798. doi: 10.1016/j.metabol.2021.154798. Epub 2021 May 11. 10.1016/j.metabol.2021.154798