PRKACA protein kinase cAMP-activated catalytic subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKACAprovided by HGNC
Official Full Name: protein kinase cAMP-activated catalytic subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:9380
See related: Ensembl:ENSG00000072062 MIM:601639; AllianceGenome:HGNC:9380
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAFD1; PKACA; PPNAD4
Summary: This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015]
Expression: Ubiquitous expression in heart (RPKM 62.0), adrenal (RPKM 43.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.12

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (14091688..14117762, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (14218299..14244374, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (14202500..14228574, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms.
Title: Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms.
PKA mediates modality-specific modulation of the mechanically gated ion channel PIEZO2.
Title: PKA mediates modality-specific modulation of the mechanically gated ion channel PIEZO2.
Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.
Title: Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems.
Defective synaptic plasticity in a model of Coffin-Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways.
Title: Defective synaptic plasticity in a model of Coffin-Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways.
Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations.
Title: Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations.
DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling.
Title: DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling.
Is Disrupted Nucleotide-Substrate Cooperativity a Common Trait for Cushing's Syndrome Driving Mutations of Protein Kinase A?
Title: Is Disrupted Nucleotide-Substrate Cooperativity a Common Trait for Cushing's Syndrome Driving Mutations of Protein Kinase A?
KARATE: PKA-induced KRAS4B-RHOA-mTORC2 supercomplex phosphorylates AKT in insulin signaling and glucose homeostasis.
Title: KARATE: PKA-induced KRAS4B-RHOA-mTORC2 supercomplex phosphorylates AKT in insulin signaling and glucose homeostasis.
Reconstitution of beta-adrenergic regulation of CaV1.2: Rad-dependent and Rad-independent protein kinase A mechanisms.
Title: Reconstitution of β-adrenergic regulation of Ca(V)1.2: Rad-dependent and Rad-independent protein kinase A mechanisms.
PKA and AKIP1 interact to mediate cAMP-driven COX-2 expression: A potentially pivotal interaction in preterm and term labour.
Title: PKA and AKIP1 interact to mediate cAMP-driven COX-2 expression: A potentially pivotal interaction in preterm and term labour.

Submit: New GeneRIF Correction See all GeneRIFs (245)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cardioacrofacial dysplasia 1 MedGen: C5436885 OMIM: 619142 GeneReviews: Not available	Compare labs
Pigmented nodular adrenocortical disease, primary, 4 MedGen: C4014425 OMIM: 615830 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 activates forward trafficking and surface clustering of NMDA receptors in membrane microdomains by a PKA-dependent phosphorylation of the NR1 C-terminal Ser897, followed by a PKC-dependent phosphorylation of Ser896	PubMed
	env	HIV-1 gp120-induced neuron death is inhibited by CCL3L1 treatment via the phosphorylation of CREB, the upregulation of Bcl-2, and the PKA and CaMKI/CaMKIV cell signaling pathways	PubMed
	env	The exposure of CD4+ T cells to HIV gp120 results in a long-lasting hyporesponsiveness to antigen stimulation through protein kinase A-mediated signaling	PubMed
	env	Treatment of normal human fibroblasts with HIV-1 gp120 protein results in a significant decrease in the levels of 8-azido-[32P]cAMP binding to RI and RII domains of protein kinase A (PKA) and in PKA activity	PubMed
Nef	nef	Serine residues Ser6 and Ser9 of HIV-1 Nef are phosphorylated by PKA in a cell-free system; intracellularly, only Ser9 of HIV-1 NL4-3 Nef is phosphorylated by PKA in resting peripheral blood mononuclear cells	PubMed
Tat	tat	The binding between HIV-1 Tat and Grb2 is mediated by the proline-rich sequence (residues 1-18) of Tat and the SH3 domain (residues 160-212) of Grb2, which impairs activation of the Raf/MAPK pathway and increases the PKA/Raf inhibitory pathway	PubMed
	tat	HIV-1 Tat-peptide(48-60) inhibits protein kinase C alpha and protein kinase A in a concentration-dependent manner	PubMed
	tat	HIV-1 Tat induces IL-6 and TNF-alpha expression through the activation of cAMP-dependent protein kinase pathways	PubMed
Vif	vif	Protein kinase A (PKA) binds and phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation	PubMed
Vpr	vpr	BiFC assays demonstrate that HIV-1 Vpr directly interacts with PKA-C alpha in HeLa cells	PubMed
	vpr	HIV-1 Vpr directly interacts with PKA and is phosphorylated at position Ser79 by PKA. PKA activity is necessary for virion-delivered Vpr cell cycle arrest	PubMed
capsid	gag	cAMP-dependent protein kinase is incorporated into HIV-1 virions, interacts with and phosphorylates the HIV-1 Capsid protein, and regulates HIV-1 infectivity	PubMed
matrix	gag	HIV-1 MA increases phosphorylation and the DNA-binding activity of CREB and c-Myc through activation of the cAMP/PKA and MEK/ERK signaling pathways. Both signaling pathways are synergistically activated upon co-stimulation through the CD19	PubMed
	gag	HIV-1 Matrix impairs proliferation of normal lymphocytes in vitro by inducing the activity of the inhibitory protein kinase A (PKA)	PubMed
	gag	Protein kinase A (PKA) has been shown to phosphorylate HIV-1 Matrix in vitro	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47780 (e-PCR)
- UniSTS:20752

RH69574 (e-PCR)
- UniSTS:67363

D1S3205 (e-PCR)
- UniSTS:43307

PRKACA__2119 (e-PCR)
- UniSTS:280925

RH65125 (e-PCR)
- UniSTS:87659

STS-N57750 (e-PCR)
- UniSTS:46029

WI-14108 (e-PCR)
- UniSTS:72672

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables cAMP-dependent protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cAMP-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cAMP-dependent protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables cAMP-dependent protein kinase activity	NAS Non-traceable Author Statement more info	PubMed
enables cAMP-dependent protein kinase activity	TAS Traceable Author Statement more info
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables manganese ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein kinase A regulatory subunit binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase A regulatory subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein serine/threonine/tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in calcium-mediated signaling using intracellular calcium source	TAS Traceable Author Statement more info	PubMed
involved_in cell communication by electrical coupling involved in cardiac conduction	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to cold	IEA Inferred from Electronic Annotation more info
involved_in cellular response to epinephrine stimulus	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to glucagon stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to parathyroid hormone stimulus	IEA Inferred from Electronic Annotation more info
involved_in cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
involved_in high-density lipoprotein particle assembly	TAS Traceable Author Statement more info
involved_in mRNA processing	IDA Inferred from Direct Assay more info	PubMed
involved_in mesoderm formation	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial protein catabolic process	TAS Traceable Author Statement more info
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of glycolytic process through fructose-6-phosphate	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of gluconeogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein export from nucleus	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in protein export from nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein kinase A signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to lipid droplet	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of bicellular tight junction assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cardiac conduction	TAS Traceable Author Statement more info
involved_in regulation of cardiac muscle contraction	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell cycle	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cytosolic calcium ion concentration	TAS Traceable Author Statement more info	PubMed
involved_in regulation of heart rate	TAS Traceable Author Statement more info	PubMed
involved_in regulation of macroautophagy	TAS Traceable Author Statement more info	PubMed
involved_in regulation of osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of proteasomal protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein binding	TAS Traceable Author Statement more info	PubMed
involved_in regulation of protein processing	IEA Inferred from Electronic Annotation more info
involved_in regulation of ryanodine-sensitive calcium-release channel activity	TAS Traceable Author Statement more info	PubMed
involved_in renal water homeostasis	TAS Traceable Author Statement more info
involved_in sperm capacitation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in acrosomal vesicle	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with axoneme	IDA Inferred from Direct Assay more info	PubMed
part_of cAMP-dependent protein kinase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of cAMP-dependent protein kinase complex	IDA Inferred from Direct Assay more info	PubMed
part_of cAMP-dependent protein kinase complex	NAS Non-traceable Author Statement more info	PubMed
part_of calcium channel complex	TAS Traceable Author Statement more info	PubMed
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary base	TAS Traceable Author Statement more info
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in neuromuscular junction	IEA Inferred from Electronic Annotation more info
located_in nuclear speck	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in sperm flagellum	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cAMP-dependent protein kinase catalytic subunit alpha

Names: PKA C-alpha; protein kinase A catalytic subunit; protein kinase, cAMP-dependent, alpha catalytic subunit; protein kinase, cAMP-dependent, catalytic, alpha

NP_001291278.1

EC 2.7.11.11

NP_002721.1

EC 2.7.11.11

NP_997401.1

EC 2.7.11.11

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029699.1 RefSeqGene

Range

4986..31060

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001304349.2 → NP_001291278.1 cAMP-dependent protein kinase catalytic subunit alpha isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' terminal exon and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 3 which has a longer and distinct N-terminus, compared to Calpha1.

Source sequence(s)

AK131561, BC039846, BC108259

Consensus CDS

CCDS92541.1

UniProtKB/TrEMBL

A0A8V8TL59

Related

ENSP00000513361.1, ENST00000350356.7

Conserved Domains (2) summary

smart00220
Location:120 → 374

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14209
Location:118 → 407

STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase
NM_002730.4 → NP_002721.1 cAMP-dependent protein kinase catalytic subunit alpha isoform Calpha1

See identical proteins and their annotated locations for NP_002721.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes Calpha1 (PMID:21812984).

Source sequence(s)

AC022098, BC039846, BU543573

Consensus CDS

CCDS12304.1

UniProtKB/Swiss-Prot

P17612, Q32P54, Q9H2Y0, Q9NRB4, Q9NRH9

UniProtKB/TrEMBL

A8K8B9

Related

ENSP00000309591.3, ENST00000308677.9

Conserved Domains (1) summary

cd14209
Location:42 → 331

STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase
NM_207518.3 → NP_997401.1 cAMP-dependent protein kinase catalytic subunit alpha isoform Calpha2

See identical proteins and their annotated locations for NP_997401.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' terminal exon and initiates translation at an alternate start codon, compared to variant 1. It encodes Calpha2, PMID:21812984 (also known as C alpha-s, PMID: 10906071) which has a shorter and distinct N-terminus, compared to Calpha1. This variant is specifically expressed in spermatogenic cells and may be essential for male fertility.

Source sequence(s)

AC022098, AK292284, BC039846, BC108259

Consensus CDS

CCDS12305.1

UniProtKB/TrEMBL

A8K8B9

Related

ENSP00000466651.1, ENST00000589994.6

Conserved Domains (1) summary

cd14209
Location:34 → 323

STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase