Human Gene PRKAR2A (uc003cux.1) Description and Page Index
  Description: Homo sapiens protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A), mRNA.
RefSeq Summary (NM_004157): 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 one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. It may interact with various A-kinase anchoring proteins and determine the subcellular localization of cAMP-dependent protein kinase. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER). [provided by RefSeq, Jul 2008]. 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 :: SRR1660803.211463.1, SRR1660805.81083.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000265563.13/ ENSP00000265563.8 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr3:48,788,093-48,885,270 Size: 97,178 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg19 chr3:48,789,018-48,885,029 Size: 96,012 Coding Exon Count: 11 

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

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr3:48,788,093-48,885,270)mRNA (may differ from genome)Protein (404 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
SUBUNIT: The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3. Interacts with the phosphorylated form of PJA2. Interacts with MYRIP. This interaction may link PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release (By similarity).
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Co-localizes with PJA2 in the cytoplasm and the cell membrane.
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: Phosphorylated by the activated catalytic chain.
SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain family.
SIMILARITY: Contains 2 cyclic nucleotide-binding domains.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PRKAR2A
CDC HuGE Published Literature: PRKAR2A

-  MalaCards Disease Associations
  MalaCards Gene Search: PRKAR2A
Diseases sorted by gene-association score: kallmann syndrome (1)

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

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 21.35 RPKM in Muscle - Skeletal
Total median expression: 366.84 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -124.00241-0.515 Picture PostScript Text
3' UTR -283.00925-0.306 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:
47391 - Dimerization-anchoring domain of cAMP-dependent type II PK regulatory subunit
51206 - cAMP-binding domain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P13861
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 orthologGenome BrowserGenome BrowserGenome BrowserNo orthologGenome Browser
Gene DetailsGene Details Gene Details Gene Details
Gene SorterGene Sorter Gene Sorter Gene Sorter
 RGDEnsemblFlyBase SGD
 Protein SequenceProtein SequenceProtein Sequence Protein Sequence
 AlignmentAlignmentAlignment Alignment

-  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:0001932 regulation of protein phosphorylation
GO:0003091 renal water homeostasis
GO:0007596 blood coagulation
GO:0034199 activation of protein kinase A activity
GO:0035556 intracellular signal transduction
GO:0071377 cellular response to glucagon stimulus
GO:2000480 negative regulation of cAMP-dependent protein kinase activity

Cellular Component:
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0005952 cAMP-dependent protein kinase complex
GO:0016020 membrane
GO:0031588 nucleotide-activated protein kinase complex
GO:0032991 macromolecular complex
GO:0044853 plasma membrane raft
GO:0070062 extracellular exosome
GO:0097546 ciliary base
GO:0005930 axoneme

-  Descriptions from all associated GenBank mRNAs
  AK293042 - Homo sapiens cDNA FLJ75444 complete cds, highly similar to Homo sapiens protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A), mRNA.
AK023535 - Homo sapiens cDNA FLJ13473 fis, clone PLACE1003592.
BC002763 - Homo sapiens protein kinase, cAMP-dependent, regulatory, type II, alpha, mRNA (cDNA clone MGC:3606 IMAGE:3629579), complete cds.
X14968 - Human testis mRNA for the RII-alpha subunit of cAMP dependent protein kinase.
JD101672 - Sequence 82696 from Patent EP1572962.
JD551599 - Sequence 532623 from Patent EP1572962.
JD114802 - Sequence 95826 from Patent EP1572962.
JD257113 - Sequence 238137 from Patent EP1572962.
BT007225 - Homo sapiens protein kinase, cAMP-dependent, regulatory, type II, alpha mRNA, complete cds.
KJ901660 - Synthetic construct Homo sapiens clone ccsbBroadEn_11054 PRKAR2A gene, encodes complete protein.
KJ905285 - Synthetic construct Homo sapiens clone ccsbBroadEn_14786 PRKAR2A gene, encodes complete protein.
KU178276 - Homo sapiens protein kinase cAMP-dependent regulatory type II alpha isoform 1 (PRKAR2A) mRNA, partial cds, alternatively spliced.
KU178277 - Homo sapiens protein kinase cAMP-dependent regulatory type II alpha isoform 2 (PRKAR2A) mRNA, partial cds.
AB464095 - Synthetic construct DNA, clone: pF1KB6582, Homo sapiens PRKAR2A gene for protein kinase, cAMP-dependent, regulatory, type II alpha, without stop codon, in Flexi system.
CU678176 - Synthetic construct Homo sapiens gateway clone IMAGE:100019171 5' read PRKAR2A mRNA.
GQ472202 - Homo sapiens epididymis secretory sperm binding protein Li 169mP (HEL-S-169mP) mRNA, complete cds.
JD458592 - Sequence 439616 from Patent EP1572962.
JD204692 - Sequence 185716 from Patent EP1572962.
JD458596 - Sequence 439620 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_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor
h_mCalpainPathway - mCalpain and friends in Cell motility
h_nos1Pathway - Nitric Oxide Signaling Pathway
h_badPathway - Regulation of BAD phosphorylation
h_vipPathway - Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells
h_cftrPathway - Cystic fibrosis transmembrane conductance regulator (CFTR) and beta 2 adrenergic receptor (b2AR) pathway
h_crebPathway - Transcription factor CREB and its extracellular signals
h_dreampathway - Repression of Pain Sensation by the Transcriptional Regulator DREAM
h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation
h_mPRPathway - How Progesterone Initiates the Oocyte Maturation
h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)
h_gpcrPathway - Signaling Pathway from G-Protein Families
h_plcePathway - Phospholipase C-epsilon pathway
h_agpcrPathway - Attenuation of GPCR Signaling
h_chrebpPathway - ChREBP regulation by carbohydrates and cAMP
h_ck1Pathway - Regulation of ck1/cdk5 by type 1 glutamate receptors
h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)
h_akap95Pathway - AKAP95 role in mitosis and chromosome dynamics
h_GATA3pathway - GATA3 participate in activating the Th2 cytokine genes expression
h_carm1Pathway - Transcription Regulation by Methyltransferase of CARM1
h_no1Pathway - Actions of Nitric Oxide in the Heart
h_shhPathway - Sonic Hedgehog (Shh) Pathway
h_stathminPathway - Stathmin and breast cancer resistance to antimicrotubule agents
h_akap13Pathway - Rho-Selective Guanine Exchange Factor AKAP13 Mediates Stress Fiber Formation
h_akapCentrosomePathway - Protein Kinase A at the Centrosome

Reactome (by CSHL, EBI, and GO)

Protein P13861 (Reactome details) participates in the following event(s):

R-HSA-9010641 AKAP5 recruits PKA to ROBO2
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-9010642 ROBO receptors bind AKAP5
R-HSA-376176 Signaling by ROBO receptors
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-422475 Axon guidance
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-1266738 Developmental Biology
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: KAP2_HUMAN, NM_004157, NP_004148, P13861, PKR2, PRKAR2, Q16823
UCSC ID: uc003cux.1
RefSeq Accession: NM_004157
Protein: P13861 (aka KAP2_HUMAN)
CCDS: CCDS2778.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_004157.2
exon count: 11CDS single in 3' UTR: no RNA size: 2381
ORF size: 1215CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2459.00frame shift in genome: no % Coverage: 100.00
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: 925# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.