Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

PRKACA

contributors: mct/shn - updated : 18-11-2020

HGNC name	protein kinase, cAMP-dependent, catalytic, alpha
HGNC id	9380

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	PPAVSD1 postaxial polydactyly with atrioventricular septal defect (AVSD) 1 PPNAD4 pigmented nodular adrenocortical disease, primary, 4
Location	19p13      Physical location : 14.202.508 - 14.228.559
Synonym name	PKA C-alpha
	protein kinase A catalytic subunit
Synonym symbol(s)	MGC102831, MGC48865, PKACa, Cs, PKA, PKCD
EC.number	2.7.11.11

DNA

TYPE	functioning gene
STRUCTURE	26.06 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

Map	pter - D19S914 - D19S840 - PRKACA - D19S892 - D19S226 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002730 10 - 2689 - 351 - 1996 8884279 NM_207518 10 - 2490 - 343 - 1996 8884279

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 Cardiovascular heart       highly Reproductive female system breast mammary gland   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a N terminus segment involved in the sensitivity to dequalinium

HOMOLOGY

interspecies	ortholog to Prkaca, Rattus norvegicus
	ortholog to Prkaca, Mus musculus

Homologene

FAMILY

PRK family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
text	PRKACA is localized at the leading edge of membrane protrusions and colocalized with WASF2

basic FUNCTION	involved in the regulation of AICDA function and in the control of T cell-dependent immune responses modulated, via AICDA, by signals that activate PRKACA
	phosphorylating AICDA and regulating its activity in germinal center B cells
	its activation is both necessary and sufficient to trigger irreversible growth arrest during keratinocyte differentiation
	critical role for its signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors CDKN1A, CDKN1B and activation of AKT1 and ERK-dependent proliferative pathways
	can negatively regulate ESR1, at least in part, through FOXH1
	key component that controls MYD88-dependent cytokine gene expression in human and mouse but differentially regulates production of TRIF-dependent cytokines
	affects cell cycle progression and proliferation in human RPE cells through the downregulation of CDKN1B
	PKCalpha-dependent stimulation of arginine transport requires the activation of MEK/ERK1/2 cascade, which leads to the stimulation of AP-1 and to the consequent induction of SLC7A2 expression
	plays an important role in redistributing GluN2BR at synapses and pain hypersensitivity (
	enhances the osteogenic function of DLX5, at least in part, through protein stabilization
	novel role of PRKACA in the regulation of RCAN1 activity through phosphorylation
	PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Calpha and Cbeta, respectively
	AKAP1-PRKACA-PDE4A distribution and integrity have a key role in cellular survival
	PRKACA directly phosphorylates ATR at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA)
	PRKACA, PRKACB playing critical role in human development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	PRKACA, AKT1 and RAPGEF3 were all shown to establish complexes with neuronal A-kinase anchoring protein 150 (AKAP5)
	WASF2-PRKACA complex is potentially localized at membrane protrusions
	SPATC1L-PRKACA complex in maintaining the stability of the sperm head-tail junction

INTERACTION

DNA

RNA

small molecule

protein	Grb2 and EGF-receptor (
	A-kinase-anchoring proteins (AKAPs) (
	PKA-interacting protein, AKIP1 (
	AKAP12 target PRKACA and other binding partners to the plasma membrane
	interactions between endogenous RPS6KA1 and PKAc in intact cells regulate the ability of cAMP to activate PRKACA
	PRKACA interacts directly with HDAC5 and phosphorylates HDAC5 at serine 280, an evolutionarily conserved site
	interaction with WASF2 (WASF2 is necessary for the localization of PRKACA under quiescent conditions as well as for membrane protrusions induced by PRKACA activation)
	interacting with DLX5 (phosphorylates DLX5 and PRKACA activation increases the protein stability, osteogenic activity and transcriptional activity of DLX5)
	PJA2 forms a stable complex with, and is phosphorylated by PRKACA
	interplay between PRKACA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis
	AKAP13 may serve an ancillary cardioprotective role by favouring the association of PRKACA with HSPB6
	PRKACA and PDE4D anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome
	direct anchoring of both PRKACA and ADCY1 to TRPV1 by AKAP5 facilitates the response to inflammatory mediators and may be critical in the pathogenesis of thermal hyperalgesia
	WEE2 acts as a direct downstream substrate of protein kinase A (PRKACA)
	anchoring of not only PRKACA but also ADCY1 by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity
	PRKACA destabilizes PP2CB upon inflammatory stimuli via phosphorylation of Ser-195 in PP2CB
	DLX3 is a novel target of PRKACA, and PRKACA mediates BMP signaling during osteoblast differentiation, at least in part, by phosphorylating DLX3 and modulating the protein stability and function of DLX3
	PRKACA regulates calcineurin function through the phosphorylation of RCAN1
	IMMT is a PRKACA substrate
	EZR-anchored PRKACA phosphorylates serine 369 and 373 on GJA1 to enhance gap junction assembly, communication, and cell fusion

cell & other

ciliary axonemes (

REGULATION

activated by	phorbol esters or thymeleatoxin which causes a transient increase of arginine transport through system y(+), referable to the induction of SLC7A2 mRNAs and to the increased expression of SLC7A2 transporters
	ABCA1 that activates PRKACA

ASSOCIATED DISORDERS

corresponding disease(s)

PPNAD4 , PPAVSD1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in colorectal cancers with constitutive activation of the Wnt-APC pathway tumoral somatic mutation       in hypothalamic hamartoma with gelastic epilepsy tumoral fusion       DNAJB1-PRKACA fusion gene characterizeshepatocellular fibrolamellar carcinoma tumoral somatic mutation       in up to 70p100 of cortisol-secreting adrenocortical adenoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression
Therapy target	hippocampal PKA inhibition by infusion of Rp-cAMPS restored long-term memory in R6/2 mice
	System Type Disorder Pubmed cancer reproductive uterus targeting PRKACA may provide novel therapeutic options in endometrial tumors cancer reproductive prostate inhibition of PKA activation, together with standard AR-targeted therapies, may be more efficacious for treatment of patients with prostate cancer

ANIMAL & CELL MODELS

	hippocampal cAMP-dependent protein kinase (PKA) hyper-activation in na
	ve R6/1 mice compared with wild-type (WT) mice, whereas extracellular signal-regulated kinase 1/2 and calcineurin activities were not modified