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

Gene ID: 5566, updated on 5-Jan-2020

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
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
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

Genomic context

See PRKACA in Genome Data Viewer
Location:
19p13.12
Exon count:
12
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (14091688..14117762, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (14202500..14228559, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene chromosome 19 open reading frame 67 Neighboring gene sterile alpha motif domain containing 1 Neighboring gene anti-silencing function 1B histone chaperone Neighboring gene uncharacterized LOC100507373 Neighboring gene adhesion G protein-coupled receptor L1

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC48865, MGC102831

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
cAMP-dependent protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
cAMP-dependent protein kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
cAMP-dependent protein kinase activity NAS
Non-traceable Author Statement
more info
PubMed 
cAMP-dependent protein kinase activity TAS
Traceable Author Statement
more info
 
magnesium ion binding IEA
Inferred from Electronic Annotation
more info
 
manganese ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IEA
Inferred from Electronic Annotation
more info
 
protein kinase A regulatory subunit binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein kinase A regulatory subunit binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein serine/threonine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein serine/threonine/tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
G2/M transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
activation of protein kinase A activity TAS
Traceable Author Statement
more info
 
blood coagulation TAS
Traceable Author Statement
more info
 
calcium-mediated signaling using intracellular calcium source TAS
Traceable Author Statement
more info
PubMed 
cell communication by electrical coupling involved in cardiac conduction TAS
Traceable Author Statement
more info
PubMed 
cellular response to epinephrine stimulus TAS
Traceable Author Statement
more info
PubMed 
cellular response to glucagon stimulus TAS
Traceable Author Statement
more info
 
cellular response to glucose stimulus IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to heat IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to parathyroid hormone stimulus IEA
Inferred from Electronic Annotation
more info
 
ciliary basal body-plasma membrane docking TAS
Traceable Author Statement
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
high-density lipoprotein particle assembly TAS
Traceable Author Statement
more info
 
mRNA processing IDA
Inferred from Direct Assay
more info
PubMed 
mesoderm formation IEA
Inferred from Electronic Annotation
more info
 
modulation of chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
 
negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning IEA
Inferred from Electronic Annotation
more info
 
neural tube closure IEA
Inferred from Electronic Annotation
more info
 
peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
peptidyl-serine phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
peptidyl-serine phosphorylation TAS
Traceable Author Statement
more info
PubMed 
peptidyl-threonine phosphorylation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of cell cycle arrest ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of protein export from nucleus IEA
Inferred from Electronic Annotation
more info
 
protein autophosphorylation IEA
Inferred from Electronic Annotation
more info
 
protein kinase A signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphorylation NAS
Non-traceable Author Statement
more info
PubMed 
regulation of G2/M transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
regulation of bicellular tight junction assembly IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cardiac conduction TAS
Traceable Author Statement
more info
 
regulation of cardiac muscle contraction TAS
Traceable Author Statement
more info
PubMed 
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion TAS
Traceable Author Statement
more info
PubMed 
regulation of cytosolic calcium ion concentration TAS
Traceable Author Statement
more info
PubMed 
regulation of heart rate TAS
Traceable Author Statement
more info
PubMed 
regulation of macroautophagy TAS
Traceable Author Statement
more info
PubMed 
regulation of osteoblast differentiation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of proteasomal protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
regulation of protein binding TAS
Traceable Author Statement
more info
PubMed 
regulation of protein processing IEA
Inferred from Electronic Annotation
more info
 
regulation of ryanodine-sensitive calcium-release channel activity TAS
Traceable Author Statement
more info
PubMed 
renal water homeostasis TAS
Traceable Author Statement
more info
 
sperm capacitation ISS
Inferred from Sequence or Structural Similarity
more info
 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
acrosomal vesicle ISS
Inferred from Sequence or Structural Similarity
more info
 
colocalizes_with axoneme IDA
Inferred from Direct Assay
more info
PubMed 
cAMP-dependent protein kinase complex IDA
Inferred from Direct Assay
more info
PubMed 
cAMP-dependent protein kinase complex NAS
Non-traceable Author Statement
more info
PubMed 
calcium channel complex TAS
Traceable Author Statement
more info
PubMed 
cell IEA
Inferred from Electronic Annotation
more info
 
centrosome IDA
Inferred from Direct Assay
more info
PubMed 
ciliary base TAS
Traceable Author Statement
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
dendritic spine IEA
Inferred from Electronic Annotation
more info
 
extracellular exosome HDA PubMed 
intercellular bridge IDA
Inferred from Direct Assay
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrion IEA
Inferred from Electronic Annotation
more info
 
neuromuscular junction IEA
Inferred from Electronic Annotation
more info
 
nuclear speck IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus HDA PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
sperm flagellum IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
cAMP-dependent protein kinase catalytic subunit alpha
Names
PKA C-alpha
cAMP-dependent protein kinase catalytic subunit alpha, isoform 1
protein kinase A catalytic subunit
protein kinase, cAMP-dependent, alpha catalytic subunit
protein kinase, cAMP-dependent, catalytic, alpha
NP_001291278.1
NP_002721.1
NP_997401.1
XP_016882437.1

NCBI Reference Sequences (RefSeq)

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

  1. NG_029699.1 RefSeqGene

    Range
    4986..31060
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001304349.1NP_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
    UniProtKB/Swiss-Prot
    P17612
    Conserved Domains (2) summary
    smart00220
    Location:120374
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14209
    Location:118407
    STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase
  2. NM_002730.4NP_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
    UniProtKB/TrEMBL
    A0A024R7J0
    Related
    ENSP00000309591.3, ENST00000308677.9
    Conserved Domains (1) summary
    cd14209
    Location:42331
    STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase
  3. NM_207518.3NP_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/Swiss-Prot
    P17612
    UniProtKB/TrEMBL
    A8K8B9
    Related
    ENSP00000466651.1, ENST00000589994.5
    Conserved Domains (1) summary
    cd14209
    Location:34323
    STKc_PKA; Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

    Range
    14091688..14117762 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017026948.1XP_016882437.1  cAMP-dependent protein kinase catalytic subunit alpha isoform X1

    Related
    ENSP00000468352.1, ENST00000587372.5

Reference GRCh38.p13 PATCHES

Genomic

  1. NW_021160022.1 Reference GRCh38.p13 PATCHES

    Range
    303847..329921 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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