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FLASH GENE

Symbol

PPP2CA

contributors: mct/npt/pgu - updated : 29-01-2019

HGNC name	protein phosphatase 2, catalytic subunit, alpha isozyme
HGNC id	9299

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

C terminal carboxyl group methylated by carboxyl methyltransferase

HOMOLOGY

Homologene

FAMILY	PPP phosphatase family
	PP-1 subfamily

CATEGORY

enzyme , tumor suppressor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus

basic FUNCTION	protein phosphatase 2A, catalytic subunit playing a pivotal role in gastrulation and neurulation in mouse
	antagonizing CDC2/CCNB1complex which regulates the G2-M transition in the cell cycle
	function as tumor suppressor protein, and important physiological regulator of cell growth and of cellular stress signaling
	appears to function as an endogenous regulator of SPHK1 phosphorylation
	interacts with epithelial tight junctions and negatively regulates the integrity of the tight junction
	in the absence of netrin-1, recruitment of PPP2CA to UNC5B allows the activation of DAPK1 via a PPP2CA-mediated dephosphorylation and this mechanism is involved in angiogenesis regulation
	by promoting the inflammatory capacity of T cells, catalytic subunit of PP2A (PP2Ac) dysregulation contributes to the pathogenesis of systemic lupus erythematosus (SLE)
	is a key negative regulator of phosphatidylinositol 3-kinase/AKT pathway
	changes in PPP2CA activity due to methylation and tyrosine phosphorylation occur in sperm and these changes may play an important role in the regulation of sperm function
	essential enzyme that is implicated as a tumor suppressor based on its central role in phosphorylation-dependent signaling pathways
	PPP2CA is required for the function of T(reg) cells and the prevention of autoimmunity
	major serine/threonine protein phosphatase, participating in multiple steps of meiosis
	regulates kinetochore-microtubule attachment during meiosis I in oocyte
	participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction
	has a critical role in the proliferation and metastasis of osteosarcoma cells
	plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor
	critical role for membrane-initiated ER signaling in metabolic homeostasis via the central action of PPP2CA
	may act as an oncogene in the progression of colorectal cancer
	importance of PPP2CA in neurodevelopmental processes and brain function

CELLULAR PROCESS	cell cycle, checkpoint

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component	complexing with a 65kDa regulatory subunit
	catalytic subunit of the ubiquitous Ser/Thr protein phosphatase PP2A could interact with the C-ter of KISS1R
	STRIPAK contains the PPP2CA, the striatins (STRN, STRN3, STRN4), MOB4, FAM40A and FAM40B, the cerebral cavernous malformation 3 (CCM3) protein, and members of the germinal center kinase III family of Ste20 kinases

INTERACTION

DNA

RNA

small molecule

protein	associating with IGBP1
	with GRM3(by Cterminal cytoplasmic tail)
	PPP2CA involvement is a molecular mechanism for FCAR ligand binding regulation, a key step in initiating an immune response
	IGBP1 plays a required role in regulating the assembly and maintenance of adaptive PPP2CA phosphatase complexes
	PPP2CA inhibiting IL23A production by suppressing the expression of the IL23A gene
	in addition to PPP2CA, IGBP1 interacts with UBR5 and PABPC1, suggesting its involvement in multiple steps in the MTOR pathway that leads to translation initiation and cell-cycle progression
	reduction of PPP2CA activity due to an enhanced IGBP1-PPP2CA interaction contributes directly to chemical carcinogen-induced tumorigenesis
	STRN, STRN32, STRN4 binds directly to PPP2CA and PDCD10
	IGBP1 interacts with MID1, a microtubule-associated ubiquitin E3 ligase that appears to regulate the function of PPP2CA
	SEMA3A elevates endothelial cell permeability through PPP2CA inactivation
	GSK3B can inhibit PPP2CA by increasing the inhibitory L309-demethylation involving upregulation of PPME1 and inhibition of LCMT1
	CABP4 is dephosphorylated by PPP2CA in the retina
	NMNAT2 affects MAPT phosphorylation by regulating PPP2CA activity
	role for MID1 in the regulation of IGBP1 that is likely to impact the stability and activity level of PPP2CA
	IGBP1 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PPP2CA) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible UBR5
	SIK2 attenuates the association of the PPP2CA repressor, the protein phosphatase methylesterase-1 (PPME1), thus preserving the methylation status of the PPP2CA catalytic subunit
	in addition to recruiting PPP2CA to dephosphorylate cohesin and CDCA5, SGO1 physically shields cohesin from WAPL
	MID1 catalyze the polyubiquitination of IGBP1, a protein regulator of protein phosphatase 2A (PPP2CA)
	STK36 ubiquitination and cleavage is one of the key elements connecting the MID1-PPP2CA protein complex with GLI3 activity control
	CIP2A interact with Protein phosphatase 2 (PPP2CA) to stabilize MYC and prevent its degradation
	PPFIA1 functioned with PPP2CA to promote the dephosphorylation of KIF7, triggering KIF7 localization to the tips of primary cilia and promoting GLI transcriptional activity
	PPME1 affects the activity of PPP2CA by demethylating PP2Ac, but also by directly binding to the phosphatase active site, suggesting loss of PPME1 in cells would enhance PPP2CA activity
	a significant fraction of total PPP6C is associated with IGBP1, whereas a minimal fraction of total PPP2CA is associated with IGBP1
	RAB9A, competes with the catalytic subunit PPP2CA in binding to PPP2R1A, which has an important role in controlling the PPP2CA catalytic activity, compromised in several solid tumors and leukemias
	regulation of protein phosphatase 2A (PPP2CA) tumor suppressor function by PPME1
	oncoprotein CIP2A is stabilized via interaction with tumor suppressor PPP2CA
	PPP2CA regulated the stem cell factor (SCF)-induced activation of MAPK14/cofilin signaling pathway and subsequent migration of cardiac stem cells (CSCs) by interaction with MAPK14

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

IDHE

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	prognostic marker in Colorectal cancer
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer PPP2CA and its regulatory subunits may be a therapeutic target for Alzheimer's disease cancer digestive colon therapeutic target in Colorectal cancer cancer bone   its inhibition could potentially suppress the malignancy of osteosarcoma cells diabete type 2   inhibition of hepatic PPP2CA may be a useful strategy for the treatment of insulin resistance syndrome

ANIMAL & CELL MODELS

double-transgenic Dom5/pR5 mice showed 7-fold increased numbers of hippocampal neurons that specifically phosphorylated the pathological S422 epitope of tau