Homo sapiens gene PRKACA, encoding protein kinase, cAMP-dependent, catalytic, alpha.
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SUMMARY back to top
RefSeq summary
[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
Expression: 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).
Function: 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
Map: 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.
Links to: , manual annotations from GAD, KEGG_04010, KEGG_04020, KEGG_04062, KEGG_04114, KEGG_04210, KEGG_04270, KEGG_04310, KEGG_04340, KEGG_04540, KEGG_04720, KEGG_04740, KEGG_04742, KEGG_04910, KEGG_04912, KEGG_04914, KEGG_04916, KEGG_04962, KEGG_04970, KEGG_05020, KEGG_05110, KEGG_05414, PhosphoSite, the SNP view, gene overviews from Entrez Gene 5566, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: 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.
EC number: This gene encodes protein number: 2.7.11.11.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene Prkaca (e=3 10-04).
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 (e=4 10-45), ATPK1 (e=4 10-45), IRE (e=4 10-41), AT1G48490 (e=6 10-41), AT2G20470 (e=2 10-40), AT3G23310 (e=2 10-40), AT4G14350 (e=2 10-39), AT1G03920 (e=7 10-39), AT1G45160 (e=10-38), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: 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 (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- 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(1000 sFPKM).
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!.
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          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the Flash version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
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.
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Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
unit
pre-mRNA
Downstream sequence
aAug10 3113 bp 427 aa 405 bp 1424 bp 57 bp 2kb including Promoter 16702 bp 1kb
bAug10 2679 bp 420 aa 1415 bp 2kb 26059 bp 1kb
cAug10 1112 bp 346 aa 69 bp 2kb 25042 bp 1kb
dAug10 2610 bp 343 aa 163 bp 1415 bp 111 bp 2kb possibly including promoter 22622 bp 1kb
eAug10 2576 bp 299 aa 770 bp 906 bp 150 bp 2kb possibly including promoter 16729 bp 1kb
fAug10 1331 bp 217 aa 395 bp 282 bp 18 bp 2kb possibly including promoter 8018 bp 1kb
gAug10 920 bp 207 aa 296 bp 2kb 10155 bp 1kb
hAug10 1101 bp 185 aa 541 bp 2kb 25697 bp 1kb
iAug10 370 bp 104 aa 53 bp 2kb 2277 bp 1kb
jAug10-unspliced 2094 bp 69 aa 367 bp 1517 bp 2kb including Promoter 2094 bp 1kb
kAug10-unspliced 375 bp 52 aa 179 bp 37 bp 2kb 375 bp 1kb

Gene neighbors and Navigator on chromosome 19p13.1 back to top
ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications         Read more...
Annotated mRNA diagrams back to top
Bibliography:               355 articles in PubMed back to top
? 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 Expression Tissue 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'.

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