Human Gene PRKAR1A (uc002jhg.4) Description and Page Index
Description: Homo sapiens protein kinase, cAMP-dependent, regulatory, type I, alpha (PRKAR1A), transcript variant 2, mRNA. RefSeq Summary (NM_212471): 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. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. 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 :: SRR1660809.157870.1, SRR1660803.199507.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## Transcript (Including UTRs) Position: hg19 chr17:66,507,921-66,529,570 Size: 21,650 Total Exon Count: 11 Strand: + Coding Region Position: hg19 chr17:66,511,541-66,526,590 Size: 15,050 Coding Exon Count: 10
ID:KAP0_HUMAN DESCRIPTION: RecName: Full=cAMP-dependent protein kinase type I-alpha regulatory subunit; AltName: Full=Tissue-specific extinguisher 1; Short=TSE1; FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. SUBUNIT: The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3 (By similarity). Interacts with PRKX; regulates this cAMP-dependent protein kinase. INTERACTION: Q9H0R8:GABARAPL1; NbExp=2; IntAct=EBI-476431, EBI-746969; Q9H8W4:PLEKHF2; NbExp=3; IntAct=EBI-476431, EBI-742388; P51817:PRKX; NbExp=2; IntAct=EBI-476431, EBI-4302903; P35250:RFC2; NbExp=7; IntAct=EBI-476431, EBI-476409; Q01105:SET; NbExp=2; IntAct=EBI-476431, EBI-1053182; TISSUE SPECIFICITY: Four types of regulatory chains are found: I- alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible. PTM: The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity. DISEASE: Defects in PRKAR1A are the cause of Carney complex type 1 (CNC1) [MIM:160980]. CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. DISEASE: Defects in PRKAR1A are the cause of intracardiac myxoma (INTMYX) [MIM:255960]. Inheritance is autosomal recessive. DISEASE: Defects in PRKAR1A are the cause of primary pigmented nodular adrenocortical disease type 1 (PPNAD1) [MIM:610489]. Primary pigmented nodular adrenocortical disease is a rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. PPNAD1 is most often diagnosed in patients with Carney complex, but it can also be observed in patients without other manifestations or familial history. DISEASE: Defects in PRKAR1A are the cause of acrodysostosis type 1, with or without hormone resistance (ACRDYS1) [MIM:101800]. ACRDYS1 is a form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone- releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities. SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain family. SIMILARITY: Contains 2 cyclic nucleotide-binding domains. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PRKAR1AID387.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PRKAR1A";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): PRKAR1A CDC HuGE Published Literature: PRKAR1A
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P10644
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LP895348 - Sequence 212 from Patent EP3253886. Y07642 - H.sapiens mRNA for cAMP-dependent protein kinase regulatory subunit RIalpha. BC093042 - Homo sapiens protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1), mRNA (cDNA clone MGC:111057 IMAGE:6514677), complete cds. BC036285 - Homo sapiens protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1), mRNA (cDNA clone MGC:17251 IMAGE:4340015), complete cds. GQ901048 - Homo sapiens clone HEL-T-160 epididymis secretory sperm binding protein mRNA, complete cds. AH003751 - Homo sapiens TSE1=protein kinase A regulatory subunit gene [human, mRNA Partial, 1033 nt 4 segments]. AK312307 - Homo sapiens cDNA, FLJ92612, Homo sapiens protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) (PRKAR1A), mRNA. CR749311 - Homo sapiens mRNA; cDNA DKFZp779L0468 (from clone DKFZp779L0468). AK124586 - Homo sapiens cDNA FLJ42595 fis, clone BRACE3010221, highly similar to cAMP-dependent protein kinase type I-alpha regulatory chain. A12295 - R1 alpha cDNA sequence. M18468 - Human cAMP-dependent protein kinase regulatory subunit type I (PRKAR1A) mRNA, complete cds. M33336 - Human cAMP-dependent protein kinase type I-alpha subunit (PRKAR1A) mRNA, complete cds. AK097580 - Homo sapiens cDNA FLJ40261 fis, clone TESTI2025609, highly similar to cAMP-dependent protein kinase type I-alpha regulatory subunit. EF428111 - Homo sapiens protein kinase A regulatory subunit type I/alpha-retinoic acid receptor alpha fusion protein isoform b (PRKAR1A/RARA fusion) mRNA, complete cds. EF428110 - Homo sapiens protein kinase A regulatory subunit type I/alpha-retinoic acid receptor alpha fusion protein isoform a (PRKAR1A/RARA fusion) mRNA, partial cds. DQ891775 - Synthetic construct clone IMAGE:100004405; FLH179817.01X; RZPDo839C01132D protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) (PRKAR1A) gene, encodes complete protein. DQ894959 - Synthetic construct Homo sapiens clone IMAGE:100009419; FLH179813.01L; RZPDo839C01131D protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) (PRKAR1A) gene, encodes complete protein. AB384780 - Synthetic construct DNA, clone: pF1KB3304, Homo sapiens PRKAR1A gene for cAMP-dependent protein kinase type I-alpha regulatory subunit, complete cds, without stop codon, in Flexi system. KJ891886 - Synthetic construct Homo sapiens clone ccsbBroadEn_01280 PRKAR1A gene, encodes complete protein. KJ905284 - Synthetic construct Homo sapiens clone ccsbBroadEn_14784 PRKAR1A gene, encodes complete protein. KR709580 - Synthetic construct Homo sapiens clone CCSBHm_00003651 PRKAR1A (PRKAR1A) mRNA, encodes complete protein. KR709581 - Synthetic construct Homo sapiens clone CCSBHm_00003656 PRKAR1A (PRKAR1A) mRNA, encodes complete protein. KR709582 - Synthetic construct Homo sapiens clone CCSBHm_00003662 PRKAR1A (PRKAR1A) mRNA, encodes complete protein. KR709583 - Synthetic construct Homo sapiens clone CCSBHm_00003668 PRKAR1A (PRKAR1A) mRNA, encodes complete protein. JD301172 - Sequence 282196 from Patent EP1572962. JD460282 - Sequence 441306 from Patent EP1572962. JD127393 - Sequence 108417 from Patent EP1572962. JD060499 - Sequence 41523 from Patent EP1572962. JD313592 - Sequence 294616 from Patent EP1572962. JD080993 - Sequence 62017 from Patent EP1572962. JD186542 - Sequence 167566 from Patent EP1572962. JD447807 - Sequence 428831 from Patent EP1572962. JD243012 - Sequence 224036 from Patent EP1572962. JD552394 - Sequence 533418 from Patent EP1572962. JD562772 - Sequence 543796 from Patent EP1572962. JD268296 - Sequence 249320 from Patent EP1572962. JD455438 - Sequence 436462 from Patent EP1572962. JD083040 - Sequence 64064 from Patent EP1572962. AL050038 - Homo sapiens mRNA; cDNA DKFZp566J0124 (from clone DKFZp566J0124). JD350567 - Sequence 331591 from Patent EP1572962. JD308526 - Sequence 289550 from Patent EP1572962. AY007115 - Homo sapiens clone TCCCTA00211 mRNA sequence. JD297201 - Sequence 278225 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04210 - Apoptosis hsa04910 - Insulin signaling pathway
BioCarta from NCI Cancer Genome Anatomy Project h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_shhPathway - Sonic Hedgehog (Shh) Pathway h_vipPathway - Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells h_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor h_GATA3pathway - GATA3 participate in activating the Th2 cytokine genes expression h_chrebpPathway - ChREBP regulation by carbohydrates and cAMP h_crebPathway - Transcription factor CREB and its extracellular signals h_agpcrPathway - Attenuation of GPCR Signaling h_badPathway - Regulation of BAD phosphorylation h_dreampathway - Repression of Pain Sensation by the Transcriptional Regulator DREAM h_gpcrPathway - Signaling Pathway from G-Protein Families h_mPRPathway - How Progesterone Initiates the Oocyte Maturation h_nos1Pathway - Nitric Oxide Signaling Pathway h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_gsPathway - Activation of cAMP-dependent protein kinase, PKA h_mCalpainPathway - mCalpain and friends in Cell motility h_no1Pathway - Actions of Nitric Oxide in the Heart h_cftrPathway - Cystic fibrosis transmembrane conductance regulator (CFTR) and beta 2 adrenergic receptor (b2AR) pathway h_ck1Pathway - Regulation of ck1/cdk5 by type 1 glutamate receptors h_plcePathway - Phospholipase C-epsilon pathway h_stathminPathway - Stathmin and breast cancer resistance to antimicrotubule agents h_carm1Pathway - Transcription Regulation by Methyltransferase of CARM1