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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:66,507,921-66,529,570)mRNA (may differ from genome)Protein (381 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsH-INV
HGNCLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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

-  MalaCards Disease Associations
  MalaCards Gene Search: PRKAR1A
Diseases sorted by gene-association score: myxoma, intracardiac* (1350), acrodysostosis 1, with or without hormone resistance* (1331), carney complex, type 1* (1218), pigmented nodular adrenocortical disease, primary, 1* (1000), primary pigmented nodular adrenocortical disease* (789), acrodysostosis* (397), carney complex variant* (368), acrodysostosis with multiple hormone resistance* (350), leukemia, acute promyelocytic, somatic* (111), cushing's syndrome (21), hyperparathyroidism, neonatal (15), hypocalcemia, autosomal dominant (14), autoimmune hypoparathyroidism (12), adrenal gland hyperfunction (12), adrenal cortical adenoma (11), neurilemmoma (11), melanocytic nevus syndrome, congenital, somatic (10), sertoli cell tumor (10), multiple endocrine neoplasia (9), multiple endocrine neoplasia 1 (8), hyperparathyroidism (8), multiple endocrine neoplasia, type iv (8), pituitary adenoma (8), myxosarcoma (7), lipomatosis (7), adrenal cortical carcinoma (7), pseudopseudohypoparathyroidism (7), mccune-albright syndrome, somatic, mosaic (7), adrenal cortex disease (7), adrenal gland disease (7), hypercalcemia, infantile, 1 (7), pituitary adenoma, prolactin-secreting (6), hormone producing pituitary cancer (6), hyperparathyroidism, familial primary (6), dysostosis (5), idiopathic hypercalciuria (5), schwannomatosis (5), nervous system benign neoplasm (4), osteoporosis (2), autosomal genetic disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 73.79 RPKM in Heart - Left Ventricle
Total median expression: 2327.50 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -163.30369-0.443 Picture PostScript Text
3' UTR -754.832980-0.253 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002373 - cAMP/cGMP_kin
IPR012198 - cAMP_dep_PK_reg_su
IPR003117 - cAMP_dep_PK_reg_su_I/II_a/b
IPR018490 - cNMP-bd-like
IPR018488 - cNMP-bd_CS
IPR000595 - cNMP-bd_dom
IPR014710 - RmlC-like_jellyroll

Pfam Domains:
PF00027 - Cyclic nucleotide-binding domain
PF02197 - Regulatory subunit of type II PKA R-subunit

SCOP Domains:
51206 - cAMP-binding domain-like

ModBase Predicted Comparative 3D Structure on P10644
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004862 cAMP-dependent protein kinase inhibitor activity
GO:0005515 protein binding
GO:0008603 cAMP-dependent protein kinase regulator activity
GO:0019904 protein domain specific binding
GO:0030552 cAMP binding
GO:0031625 ubiquitin protein ligase binding
GO:0034236 protein kinase A catalytic subunit binding

Biological Process:
GO:0001707 mesoderm formation
GO:0001932 regulation of protein phosphorylation
GO:0003091 renal water homeostasis
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006469 negative regulation of protein kinase activity
GO:0007143 female meiotic division
GO:0007507 heart development
GO:0007596 blood coagulation
GO:0034199 activation of protein kinase A activity
GO:0035556 intracellular signal transduction
GO:0045214 sarcomere organization
GO:0045835 negative regulation of meiotic nuclear division
GO:0045859 regulation of protein kinase activity
GO:0046007 negative regulation of activated T cell proliferation
GO:0060038 cardiac muscle cell proliferation
GO:0071377 cellular response to glucagon stimulus
GO:2000480 negative regulation of cAMP-dependent protein kinase activity

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005952 cAMP-dependent protein kinase complex
GO:0016020 membrane
GO:0031588 nucleotide-activated protein kinase complex
GO:0031594 neuromuscular junction
GO:0032991 macromolecular complex
GO:0044853 plasma membrane raft
GO:0097546 ciliary base
GO:0001772 immunological synapse
GO:0005930 axoneme


-  Descriptions from all associated GenBank mRNAs
  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

Reactome (by CSHL, EBI, and GO)

Protein P10644 (Reactome details) participates in the following event(s):

R-HSA-992708 Dual-specific AKAPs bind type I and II PKA regulatory subunits
R-HSA-8951727 cAMP binds PKA tetramer
R-HSA-111925 cAMP induces dissociation of inactive PKA tetramers
R-HSA-5610749 cAMP dissociates PKA, promoting GLI processing
R-HSA-381707 PKA:AKAP79:IQGAP1 complex dissociates to active PKA subunits in response to cAMP
R-HSA-983231 Factors involved in megakaryocyte development and platelet production
R-HSA-163615 PKA activation
R-HSA-180024 DARPP-32 events
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-164378 PKA activation in glucagon signalling
R-HSA-5610787 Hedgehog 'off' state
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-109582 Hemostasis
R-HSA-111931 PKA-mediated phosphorylation of CREB
R-HSA-111885 Opioid Signalling
R-HSA-445717 Aquaporin-mediated transport
R-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-5358351 Signaling by Hedgehog
R-HSA-422356 Regulation of insulin secretion
R-HSA-111933 Calmodulin induced events
R-HSA-418594 G alpha (i) signalling events
R-HSA-382551 Transport of small molecules
R-HSA-163685 Energy Metabolism
R-HSA-162582 Signal Transduction
R-HSA-111997 CaM pathway
R-HSA-388396 GPCR downstream signalling
R-HSA-1430728 Metabolism
R-HSA-111996 Ca-dependent events
R-HSA-1489509 DAG and IP3 signaling
R-HSA-372790 Signaling by GPCR
R-HSA-112043 PLC beta mediated events
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-112040 G-protein mediated events

-  Other Names for This Gene
  Alternate Gene Symbols: KAP0_HUMAN, NM_212471, NP_997637, P10644, PKR1, PRKAR1, Q567S7, TSE1, uc002jhg.3
UCSC ID: uc002jhg.4
RefSeq Accession: NM_212471
Protein: P10644 (aka KAP0_HUMAN)
CCDS: CCDS11678.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PRKAR1A:
carney (Carney Complex)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_212471.2
exon count: 11CDS single in 3' UTR: no RNA size: 4518
ORF size: 1146CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2270.00frame shift in genome: no % Coverage: 99.49
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.