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

    Gene ID: 5566, updated on 3-Nov-2024

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See PRKACA in Genome Data Viewer
    Location:
    19p13.12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (14091688..14117762, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (14218299..14244374, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (14202500..14228574, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14153 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14154 Neighboring gene chromosome 19 open reading frame 67 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:14199415-14199924 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10228 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10229 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10230 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10231 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10232 Neighboring gene MPRA-validated peak3379 silencer Neighboring gene sterile alpha motif domain containing 1 Neighboring gene Sharpr-MPRA regulatory region 14201 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:14223743-14224430 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10233 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10234 Neighboring gene uncharacterized LOC124904642 Neighboring gene small integral membrane protein 46 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14155 Neighboring gene anti-silencing function 1B histone chaperone Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10235 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14156 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:14247764-14248390 Neighboring gene ADGRL1 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 12148 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:14258690-14259433 Neighboring gene adhesion G protein-coupled receptor L1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:14278263-14278762

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues 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

    Clone Names

    • MGC48865, MGC102831

    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 channel activator activity TAS
    Traceable Author Statement
    more info
    PubMed 
    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 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cAMP/PKA signal transduction IDA
    Inferred from Direct Assay
    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 interleukin-2 production ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    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 positive regulation of calcium-mediated signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of cholesterol biosynthetic process IDA
    Inferred from Direct Assay
    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 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 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 processing IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in renal water homeostasis TAS
    Traceable Author Statement
    more info
     
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    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 extracellular exosome HDA 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
     
    part_of nucleotide-activated protein kinase complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus HDA 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 postsynapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in sperm flagellum IEA
    Inferred from Electronic Annotation
    more info
     
    located_in sperm midpiece IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    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
    NP_002721.1
    NP_997401.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_001304349.2 → 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
    2. 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
    3. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

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

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_021160022.1 Reference GRCh38.p14 PATCHES

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      14218299..14244374 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)