[PRKACA] cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. 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. The protein encoded by this gene is a member of the Ser/Thr protein kinase family and is a catalytic subunit of cAMP-dependent protein kinase. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq].
RefSeq annotates 2 representative transcripts (NM included in AceView variants .b and .d), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 9 spliced variants
AceView synopsis, each blue text links to tables and details
According to AceView, this gene is expressed at high level
, 3.7 times the average gene in this release. The sequence
of this gene is defined by 433 GenBank accessions
from 360 cDNA clones, some from brain (seen 30 times), breast (23), prostate (20), eye (17), colon (15), liver and spleen (15), lung (15) and 130 other tissues
. We annotate structural defects or features
in 83 cDNA clones.
Alternative mRNA variants and regulation:
The gene contains 15 distinct gt-ag introns
. Transcription produces 11 different mRNAs
, 9 alternatively spliced variants and 2 unspliced forms. There are 6 probable alternative promotors
, 4 non overlapping alternative last exons and 6 validated alternative polyadenylation sites
(see the diagram
). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 7 cassette exons
, splicing versus retention of one intron.
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF
) initiating at an AUG upstream of the main open reading frame (in variant aAug10, dAug10, eAug10, fAug10).
There are 355 articles
specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases
(Adrenal Gland Neoplasms; Cholesterol, HDL/blood*; Glioma; Leukemia, Myeloid; Liver Neoplasms; Long QT Syndrome; Melanoma; Neuroblastoma; Pheochromocytoma; Prostatic Neoplasms), proposed to participate in pathways
(Activation of cAMP-dependent protein kinase PKA, Apoptosis, Calcium signaling pathway, Chemokine signaling pathway, Dilated cardiomyopathy, Gap junction, GnRH signaling pathway, Hedgehog signaling pathway, Insulin signaling pathway, Long-term potentiation, MAPK signaling pathway, Melanogenesis, Olfactory transduction, Oocyte meiosis, Prion diseases, Progesterone-mediated oocyte maturation, Salivary secretion, Taste transduction, Vascular smooth muscle contraction, Vasopressin-regulated water reabsorption, Vibrio cholerae infection, Wnt signaling pathway) and processes
(mesoderm formation, negative regulation of meiotic cell cycle, peptidyl-serine phosphorylation, positive regulation of protein export from nucleus, protein amino acid autophosphorylation, regulation of cellular respiration, regulation of synaptic transmission, glutamatergic). Proteins are expected to have molecular functions
(ATP binding, nucleotide binding, protein complex binding, protein serine/threonine kinase activity, transferase activity) and to localize
in various compartments (cytoplasm, Golgi apparatus, mitochondrion, neuromuscular junction and 4 others
). Putative protein interactors
have been described (AANAT, ABCA1, ABCB8ANDACCN3, ACCN2, ACLY, ADCY5, ADD1, ADD2, ADRBK1, AKAP8L, APCANDSRP19ANDZRSR1, APOBEC3G, ARSGANDPRKAR1A, ATF1, ATP2B1, AURKA, BAD, BCL2, BRAF, BTRC, C7ORF16, C11ORF17, CACNA1C, CACNG2, CAD, CAMKK2, CAV2ANDCAV1, CCND1, CDK16, CETN1, CFTR, CIITA, CLDN3, CNPY3ANDGNMT, CREB1, CREM, CSK, CUL5, DSP, EEF2K, EGFR, EPB49, ERFANDGSK3A, ESR1, ETV1, FAM96BANDRRAD, FOS, FXYD1ANDFXYD7, GABRB3, GABRR1, GAD1, GAD2, GFAP, GJA5, GJB1, GMFB, GNA13, GPR156ANDGSK3B, GRIA1, GRIA4, GUSB, GYS1, HAND1, HAND2, HDAC8, HMGCR, HMGN1, HMGN2, HNRNPD, HSPD1, IFNAR1, IQGAP1, IRF2, ITGA4, ITPKA, ITPKB, ITPR1, ITPR2, KCNH2, KCNJ12, KCNQ1, KLF1, LCK, LCP1, LIPE, LRP1, MAP2, MAP3K3, MBP, MC4R, MED20ANDUSP49, MEP1B, MGMT, MIP, NDRG1, NDUFA1ANDAKAP14, NFKB1, NIN, NMT1, NOLC1, NOS1, NPR1 and 60 others
Protein coding potential:
9 spliced mRNAs putatively encode good proteins
, altogether 9 different isoforms (4 complete, 5 COOH complete
), some containing domains
Protein kinase domain, Protein tyrosine kinase [Pfam]. The remaining 2 mRNA variants (2 unspliced) appear not to encode good proteins.
Isoform PRKACA.eAug10 is annotated using as Met a Kozak-compatible
g..AGGg start, thereby gaining 70 amino acids N-terminal to the first AUG. Finally proteins from this gene may be modulated by acetylation; phosphorylation; ubiquitination
, as detailed at PhosphoSite.
Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12
Map on chromosome 19, links to other databases and other names
This gene PRKACA maps on chromosome 19, at 19p13.1 according to Entrez Gene. In AceView, it covers 26.40 kb
, from 14228896 to 14202495 (NCBI 37, August 2010), on the reverse strand.
, manual annotations from GAD
, the SNP
view, gene overviews from Entrez Gene 5566
, expression data from ECgene
, molecular and other annotations from UCSC
, or our GOLD
The previous AceView annotation is here
The gene is also known as PRKACA, PKACA, MGC48865, MGC102831, LOC5566 or snarcho, snuweeby. It has been described as cAMP-dependent protein kinase catalytic subunit alpha, PKA C-alpha, protein kinase A catalytic subunit, cAMP-dependent protein kinase catalytic subunit alpha, isoform 1.
This gene encodes protein number: 126.96.36.199.
Closest AceView homologs in other species
The closest mouse gene
, according to BlastP, is the AceView gene Prkaca
The closest C.elegans gene
, according to BlastP, is the AceView/WormGene kin-1
(e=0.78), which may contain interesting functional annotation.
The closest A.thaliana genes
, according to BlastP, are the AceView genes ATPK19
), which may contain interesting functional annotation
Complete gene on genome diagram:
Compact gene diagram
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project
- Primates: Apes
: Human (Illumina BodyMap 2), CHP
: Chimpanzee), Old World monkeys
: Pig-Tailed Macaque, JMI
Japanese Macaque, RMI
Rhesus Macaque Indian, RMC
Rhesus Macaque Chinese, CMM
Cynomolgus Macaque Mauritian, CMC
Cynomolgus Macaque Chinese, BAB
Olive Baboon, SMY
Sooty Mangabey); New World monkeys
common Marmoset, SQM
Squirrel Monkey, OWL
Owl Monkey); and Lemurs
Mouse Lemur, RTL
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue)
and for this gene (green)
, in Magic index = log2
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC
, by tissue or by species. Tracks may be slow to load
; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
About UCSC tracks: you may enjoy the plots for the summed coverage over all primates' libraries (top track), summarizing 3 terabases of stranded RNA-seq. Fragments mapping on the + strand of the genome (from genes on the + strand) are red (or dark), on minus strand blue (or light) and antisense transcribed areas are black or overlaid. The vertical scale for each track is self-adapting. Homozygous SNPs tracks are also presented.
About mapping: Primates body map RNA-seq data were stringently mapped to the human genome using the NCBI Magic pipeline. Normalized results are shown as significant FPKM (sFPKM), which includes corrections on F, K and M, computed from parameters measured directly in each RNA-seq experiment, to render the expression measures more significant and more robust to experimental biases. Only fragments with both reads mapped uniquely and over at least 80+80 bases ending with 8 exact bases on each side of each read, and facing each other in a single site or gene, are included in the computation of the sFPKM/index, in the coverage plots, and in the determination of homozygous SNPs (minimum coverage 10, minimum allele frequency 95%). But be aware that genes whose sequence evolved to become too distant from Human cannot be measured well, this bias can be appreciated in the per-species coverage plots at UCSC.
About libraries: For non-human primates, total RNA libraries used TruSeq, ribozero and the stranded UDG protocol. The human 2010 libraries used the polyA selected non-stranded protocol, with short reads (50, 75 or 50+50 bases); furthermore the insert lengths are larger in human than in the non-human primates (average insert size 187 bp in non-human primates versus 232 bp in human). These protocol differences may impact expression measures for the non polyadenylated genes (or genes with shorter or occasional polyA tails), for the pseudogenes or close gene families (specificity is reduced in humans due to shorter reads), and for the very short genes.
Sequences: click on the numbers to get the DNA
Gene neighbors and Navigator on chromosome 19p13.1
Annotated mRNA diagrams
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Mouse over the ending of each transcript gives tissues from which the supporting cDNAs were extracted. Details on tissue of origin for each intron and exon is available from the intron and exons table
Click on any transcript to open the specific mRNA page, to see the exact cDNA clone support and eventual SNPs and to get details on tissues, sequences, mRNA and protein annotations. Proteins supported by a single continuous cDNA sequence lead to underlining the name/ending of the variant. Names not underlined result from cDNA concatenation in the coding region and should be experimentally checked.
are depicted by broken lines; the height of the top of each intron reflects the relative number of clones supporting this intron. ]^[ A pink broken line
denotes an intron with standard boundaries (gt-ag or gc-ag) that is exactly supported (i.e. a cDNA sequence exactly matches the genome over 16 bp, 8 on both sides of the intron). ] ^ ] A blue broken line
denotes non-standard introns, exactly supported, but with non-standard at-ac or any other boundaries. ]-[ Pink
and ] - ] blue
straight lines represent 'fuzzy' introns of the standard and non-standard types respectively, those introns do not follow the 16 bp rule. Black straight lines ]-[denote gaps in the alignments.
Wide filled pink areas represent putative protein coding regions, narrow empty pink boxes represent the 5'UTR (on the left) and 3' UTR (on the right). Flags identify validated endings: cap site on the 5' side, polyadenylation site on the 3' side. Filled flags correspond to frequent events while empty flags have lesser supporting cDNAs (yet all are validated); at the 3' side, black flags are associated to the main AATAAA signal, blue flags
to any single letter variant of the main . More explanations are given in the gene help file
Bibliography:   355 articles in PubMed
The mRNAs diagrams with the aligned cDNA sequence accessions and their mismatches are available in the mRNA pages accessible from the tab at the top of the page, or here:
In Flash: .a, .i, .b, .d, .j-u, .e, .k-u, .h, .c, .g, .f
or in GIF: .a, .i, .b, .d, .j-u, .e, .k-u, .h, .c, .g, .f
|? ||Gene Summary
||Gene on genome
||mRNA:.a, .b, .c, .d, .e, .f, .g, .h, .i, .j-u, .k-u
||Alternative mRNAs features, proteins, introns, exons, sequences
||Function, regulation, related genes DCI
To mine knowledge
about the gene, please click the 'Gene Summary'
or the 'Function, regulation, related genes '
tab at the top of the page. The 'Gene Summary'
page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes '
page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants
, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features'
tab. To see a specific mRNA variant
diagram, sequence and annotation, click the variant name in the 'mRNA'
tab. To examine expression data
from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'
If you know more about this gene, or found errors, please share
your knowledge. Thank you !