LOCUS       NM_002730               2695 bp    mRNA    linear   PRI 15-MAR-2025
DEFINITION  Homo sapiens protein kinase cAMP-activated catalytic subunit alpha
            (PRKACA), transcript variant 1, mRNA.
ACCESSION   NM_002730
VERSION     NM_002730.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2695)
  AUTHORS   Shirani,M., Levin,S., Shebl,B., Requena,D., Finkelstein,T.M.,
            Johnson,D.S., Ng,D., Lalazar,G., Heissel,S., Hojrup,P., Molina,H.,
            de Jong,Y.P., Rice,C.M., Singhi,A.D., Torbenson,M.S., Coffino,P.,
            Lyons,B. and Simon,S.M.
  TITLE     Increased Protein Kinase A Activity Induces Fibrolamellar
            Hepatocellular Carcinoma Features Independent of DNAJB1
  JOURNAL   Cancer Res 84 (16), 2626-2644 (2024)
   PUBMED   38888469
  REMARK    GeneRIF: Increased Protein Kinase A Activity Induces Fibrolamellar
            Hepatocellular Carcinoma Features Independent of DNAJB1.
REFERENCE   2  (bases 1 to 2695)
  AUTHORS   Tanaka,M., Takeshita,K., Kunita,A., Hasegawa,K. and Ushiku,T.
  TITLE     PRKACA/PRKACB Fusions in Pancreatobiliary Intraductal Oncocytic
            Papillary Neoplasms Including Those With Atypical Morphology: An
            Analysis of 22 Cases Expanding Morphologic Spectrum
  JOURNAL   Am J Surg Pathol 48 (8), 1032-1040 (2024)
   PUBMED   38841868
  REMARK    GeneRIF: PRKACA/PRKACB Fusions in Pancreatobiliary Intraductal
            Oncocytic Papillary Neoplasms Including Those With Atypical
            Morphology: An Analysis of 22 Cases Expanding Morphologic Spectrum.
REFERENCE   3  (bases 1 to 2695)
  AUTHORS   Beuschlein,F., Fassnacht,M., Assie,G., Calebiro,D., Stratakis,C.A.,
            Osswald,A., Ronchi,C.L., Wieland,T., Sbiera,S., Faucz,F.R.,
            Schaak,K., Schmittfull,A., Schwarzmayr,T., Barreau,O., Vezzosi,D.,
            Rizk-Rabin,M., Zabel,U., Szarek,E., Salpea,P., Forlino,A.,
            Vetro,A., Zuffardi,O., Kisker,C., Diener,S., Meitinger,T.,
            Lohse,M.J., Reincke,M., Bertherat,J., Strom,T.M. and Allolio,B.
  TITLE     Constitutive activation of PKA catalytic subunit in adrenal
            Cushing's syndrome
  JOURNAL   N Engl J Med 370 (11), 1019-1028 (2014)
   PUBMED   24571724
  REMARK    GeneRIF: Genetic alterations of the catalytic subunit of PKA were
            found to be associated with bilateral adrenal hyperplasias and
            unilateral cortisol-producing adrenal adenomas.
REFERENCE   4  (bases 1 to 2695)
  AUTHORS   Agustin,J.T., Wilkerson,C.G. and Witman,G.B.
  TITLE     The unique catalytic subunit of sperm cAMP-dependent protein kinase
            is the product of an alternative Calpha mRNA expressed specifically
            in spermatogenic cells
  JOURNAL   Mol Biol Cell 11 (9), 3031-3044 (2000)
   PUBMED   10982398
REFERENCE   5  (bases 1 to 2695)
  AUTHORS   Reinton,N., Orstavik,S., Haugen,T.B., Jahnsen,T., Tasken,K. and
            Skalhegg,B.S.
  TITLE     A novel isoform of human cyclic 3',5'-adenosine
            monophosphate-dependent protein kinase, c alpha-s, localizes to
            sperm midpiece
  JOURNAL   Biol Reprod 63 (2), 607-611 (2000)
   PUBMED   10906071
REFERENCE   6  (bases 1 to 2695)
  AUTHORS   Desseyn,J.L., Burton,K.A. and McKnight,G.S.
  TITLE     Expression of a nonmyristylated variant of the catalytic subunit of
            protein kinase A during male germ-cell development
  JOURNAL   Proc Natl Acad Sci U S A 97 (12), 6433-6438 (2000)
   PUBMED   10841548
REFERENCE   7  (bases 1 to 2695)
  AUTHORS   Da Silva,J.D., Tkachenko,N. and Soares,A.R.
  TITLE     Ellis-van Creveld Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   37903214
REFERENCE   8  (bases 1 to 2695)
  AUTHORS   Maldonado,F. and Hanks,S.K.
  TITLE     A cDNA clone encoding human cAMP-dependent protein kinase catalytic
            subunit C alpha
  JOURNAL   Nucleic Acids Res 16 (16), 8189-8190 (1988)
   PUBMED   2843813
REFERENCE   9  (bases 1 to 2695)
  AUTHORS   Shoji,S., Titani,K., Demaille,J.G. and Fischer,E.H.
  TITLE     Sequence of two phosphorylated sites in the catalytic subunit of
            bovine cardiac muscle adenosine 3':5'-monophosphate-dependent
            protein kinase
  JOURNAL   J Biol Chem 254 (14), 6211-6214 (1979)
   PUBMED   221492
REFERENCE   10 (bases 1 to 2695)
  AUTHORS   Joh,T.H., Park,D.H. and Reis,D.J.
  TITLE     Direct phosphorylation of brain tyrosine hydroxylase by cyclic
            AMP-dependent protein kinase: mechanism of enzyme activation
  JOURNAL   Proc Natl Acad Sci U S A 75 (10), 4744-4748 (1978)
   PUBMED   33381
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC022098.9, BU543573.1 and
            BC039846.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_002730.3.
            
            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].
            
            Transcript Variant: This variant (1) encodes Calpha1
            (PMID:21812984).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC039846.1, X07767.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000308677.9/ ENSP00000309591.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-15                AC022098.9         155125-155139       c
            16-21               BU543573.1         1-6
            22-2695             BC039846.1         3-2676
FEATURES             Location/Qualifiers
     source          1..2695
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.12"
     gene            1..2695
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /note="protein kinase cAMP-activated catalytic subunit
                     alpha"
                     /db_xref="GeneID:5566"
                     /db_xref="HGNC:HGNC:9380"
                     /db_xref="MIM:601639"
     exon            1..261
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     CDS             216..1271
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /EC_number="2.7.11.11"
                     /note="isoform Calpha1 is encoded by transcript variant 1;
                     protein kinase A catalytic subunit; PKA C-alpha; protein
                     kinase, cAMP-dependent, catalytic, alpha; protein kinase,
                     cAMP-dependent, alpha catalytic subunit"
                     /codon_start=1
                     /product="cAMP-dependent protein kinase catalytic subunit
                     alpha isoform Calpha1"
                     /protein_id="NP_002721.1"
                     /db_xref="CCDS:CCDS12304.1"
                     /db_xref="GeneID:5566"
                     /db_xref="HGNC:HGNC:9380"
                     /db_xref="MIM:601639"
                     /translation="MGNAAAAKKGSEQESVKEFLAKAKEDFLKKWESPAQNTAHLDQF
                     ERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFP
                     FLVKLEFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHS
                     LDLIYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNK
                     AVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQV
                     DLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAPFIPKFKGPGDTSNFDDYEEE
                     EIRVSINEKCGKEFSEF"
     exon            262..323
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            324..452
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            453..551
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            552..634
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            635..761
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            762..857
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            858..980
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            981..1145
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1146..2695
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /inference="alignment:Splign:2.1.0"
     polyA_site      1840
                     /gene="PRKACA"
                     /gene_synonym="CAFD1; PKACA; PPNAD4"
                     /note="major polyA site"
ORIGIN      
        1 acagacagcg gcagagatct tgggctgagg ttcccgggcg ggcgggcgcg gagagacgcg
       61 ggaagcaggg gctgggcggg ggtcgcggcg ccgcagctag cgcagccagc ccgagggccg
      121 ccgccgccgc cgcccagcgc gctccggggc cgccggccgc agccagcacc cgccgcgccg
      181 cagctccggg accggccccg gccgccgccg ccgcgatggg caacgccgcc gccgccaaga
      241 agggcagcga gcaggagagc gtgaaagaat tcttagccaa agccaaagaa gattttctta
      301 aaaaatggga aagtcccgct cagaacacag cccacttgga tcagtttgaa cgaatcaaga
      361 ccctcggcac gggctccttc gggcgggtga tgctggtgaa acacaaggag accgggaacc
      421 actatgccat gaagatcctc gacaaacaga aggtggtgaa actgaaacag atcgaacaca
      481 ccctgaatga aaagcgcatc ctgcaagctg tcaactttcc gttcctcgtc aaactcgagt
      541 tctccttcaa ggacaactca aacttataca tggtcatgga gtacgtgccc ggcggggaga
      601 tgttctcaca cctacggcgg atcggaaggt tcagtgagcc ccatgcccgt ttctacgcgg
      661 cccagatcgt cctgaccttt gagtatctgc actcgctgga tctcatctac agggacctga
      721 agccggagaa tctgctcatt gaccagcagg gctacattca ggtgacagac ttcggtttcg
      781 ccaagcgcgt gaagggccgc acttggacct tgtgcggcac ccctgagtac ctggcccctg
      841 agattatcct gagcaaaggc tacaacaagg ccgtggactg gtgggccctg ggggttctta
      901 tctatgaaat ggccgctggc tacccgccct tcttcgcaga ccagcccatc cagatctatg
      961 agaagatcgt ctctgggaag gtgcgcttcc cttcccactt cagctctgac ttgaaggacc
     1021 tgctgcggaa cctcctgcag gtagatctca ccaagcgctt tgggaacctc aagaatgggg
     1081 tcaacgatat caagaaccac aagtggtttg ccacaactga ctggattgcc atctaccaga
     1141 ggaaggtgga agctcccttc ataccaaagt ttaaaggccc tggggatacg agtaactttg
     1201 acgactatga ggaagaagaa atccgggtct ccatcaatga gaagtgtggc aaggagtttt
     1261 ctgagtttta ggggcatgcc tgtgccccca tgggttttct tttttctttt ttcttttttt
     1321 tggtcggggg ggtgggaggg ttggattgaa cagccagagg gccccagagt tccttgcatc
     1381 taatttcacc cccaccccac cctccagggt tagggggagc aggaagccca gataatcaga
     1441 gggacagaaa caccagctgc tccccctcat ccccttcacc ctcctgcccc ctctcccact
     1501 tttcccttcc tctttcccca cagcccccca gcccctcagc cctcccagcc cacttctgcc
     1561 tgttttaaac gagtttctca actccagtca gaccaggtct tgctggtgta tccagggaca
     1621 gggtatggaa agaggggctc acgcttaact ccagccccca cccacacccc catcccaccc
     1681 aaccacaggc cccacttgct aagggcaaat gaacgaagcg ccaaccttcc tttcggagta
     1741 atcctgcctg ggaaggagag atttttagtg acatgttcag tgggttgctt gctagaattt
     1801 ttttaaaaaa acaacaattt aaaatcttat ttaagttcca ccagtgcctc cctccctcct
     1861 tcctctactc ccacccctcc catgtccccc cattcctcaa atccatttta aagagaagca
     1921 gactgacttt ggaaagggag gcgctggggt ttgaacctcc ccgctgctaa tctcccctgg
     1981 gcccctcccc ggggaatcct ctctgccaat cctgcgaggg tctaggcccc tttaggaagc
     2041 ctccgctctc tttttcccca acagacctgt cttcaccctt gggctttgaa agccagacaa
     2101 agcagctgcc cctctccctg ccaaagagga gtcatccccc aaaaagacag agggggagcc
     2161 ccaagcccaa gtctttcctc ccagcagcgt ttccccccaa ctccttaatt ttattctccg
     2221 ctagatttta acgtccagcc ttccctcagc tgagtgggga gggcatccct gcaaaaggga
     2281 acagaagagg ccaagtcccc ccaagccacg gcccggggtt caaggctaga gctgctgggg
     2341 aggggctgcc tgttttactc acccaccagc ttccgcctcc cccatcctgg gcgcccctcc
     2401 tccagcttag ctgtcagctg tccatcacct ctcccccact ttctcatttg tgcttttttc
     2461 tctcgtaata gaaaagtggg gagccgctgg ggagccaccc cattcatccc cgtatttccc
     2521 cctctcataa cttctcccca tcccaggagg agttctcagg cctggggtgg ggccccgggt
     2581 gggtgcgggg gcgattcaac ctgtgtgctg cgaaggacga gacttcctct tgaacagtgt
     2641 gctgttgtaa acatatttga aaactattac caataaagtt ttgtttaaaa aaaaa
//
