PRKAR2A

cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene.

PRKAR2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2IZX, 2KYG, 4ZP3
Identifiers
Aliases	PRKAR2A, PKR2, PRKAR2, protein kinase cAMP-dependent type II regulatory subunit alpha
External IDs	OMIM: 176910; MGI: 108025; HomoloGene: 3064; GeneCards: PRKAR2A; OMA:PRKAR2A - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3p21.31 Start 48,744,597 bp End 48,847,874 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9|9 F2 Start 108,566,513 bp End 108,627,635 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell oocyte secondary oocyte Skeletal muscle tissue of rectus abdominis olfactory bulb Skeletal muscle tissue of biceps brachii endothelial cell deltoid muscle tendon of biceps brachii tibialis anterior muscle Top expressed in habenula Paneth cell ankle triceps brachii muscle migratory enteric neural crest cell hair follicle retinal pigment epithelium sternocleidomastoid muscle digastric muscle muscle of thigh More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein kinase A catalytic subunit binding cAMP binding protein binding cAMP-dependent protein kinase regulator activity cAMP-dependent protein kinase inhibitor activity ubiquitin protein ligase binding protein domain specific binding 3',5'-cyclic-GMP phosphodiesterase activity Cellular component cytoplasm cytosol centrosome membrane focal adhesion plasma membrane raft plasma membrane ciliary base nucleotide-activated protein kinase complex extracellular exosome axoneme cAMP-dependent protein kinase complex protein-containing complex Biological process regulation of protein phosphorylation activation of protein kinase A activity intracellular signal transduction cellular response to glucagon stimulus blood coagulation negative regulation of cAMP-dependent protein kinase activity renal water homeostasis cGMP-mediated signaling binding of sperm to zona pellucida Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5576 19087 Ensembl ENSG00000114302 ENSMUSG00000032601 UniProt P13861 P12367 RefSeq (mRNA) NM_004157 NM_001321982 NM_001321983 NM_001321989 NM_008924 RefSeq (protein) NP_001308911 NP_001308912 NP_001308918 NP_004148 n/a Location (UCSC) Chr 3: 48.74 – 48.85 Mb Chr 9: 108.57 – 108.63 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent Protein Kinase, more commonly called Protein Kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA 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 of PKA 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 (AKAPs) and determine the subcellular localization of PKA. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER).

Interactions

PRKAR2A has been shown to interact with:

• AKAP11,
• AKAP13,
• AKAP1,
• AKAP2,
• AKAP3,
• AKAP8,
• AKAP9,
• ARFGEF2,
• CBFA2T3
• GSK3B,
• PDE4A, and
• RUNX1T1.

See also

• Protein kinase
• AMPK
• cAMP

Further reading

• Cho-Chung YS, Nesterova MV (Nov 2005). "Tumor reversion: protein kinase A isozyme switching". Annals of the New York Academy of Sciences. 1058 (1): 76–86. Bibcode:2005NYASA1058...76C. doi:10.1196/annals.1359.014. PMID 16394127. S2CID 45471438.
• Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (Dec 2006). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets. 7 (12): 1595–606. doi:10.2174/138945006779025338. PMID 17168834.
• Skålhegg BS, Landmark B, Foss KB, Lohmann SM, Hansson V, Lea T, Jahnsen T (Mar 1992). "Identification, purification, and characterization of subunits of cAMP-dependent protein kinase in human testis. Reverse mobilities of human RII alpha and RII beta on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with rat and bovine RIIs". The Journal of Biological Chemistry. 267 (8): 5374–9. doi:10.1016/S0021-9258(18)42776-7. PMID 1544918.
• Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD (Jul 1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". The Journal of Biological Chemistry. 267 (19): 13376–82. doi:10.1016/S0021-9258(18)42221-1. PMID 1618839.
• Hofmann B, Nishanian P, Baldwin RL, Insixiengmay P, Nel A, Fahey JL (Dec 1990). "HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism". Journal of Immunology. 145 (11): 3699–705. doi:10.4049/jimmunol.145.11.3699. PMID 1978848.
• Scott JD, Stofko RE, McDonald JR, Comer JD, Vitalis EA, Mangili JA (Dec 1990). "Type II regulatory subunit dimerization determines the subcellular localization of the cAMP-dependent protein kinase". The Journal of Biological Chemistry. 265 (35): 21561–6. doi:10.1016/S0021-9258(18)45777-8. PMID 2147685.
• Oyen O, Myklebust F, Scott JD, Hansson V, Jahnsen T (Mar 1989). "Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent protein kinase encodes an alternate amino-terminal region". FEBS Letters. 246 (1–2): 57–64. doi:10.1016/0014-5793(89)80253-4. PMID 2540040. S2CID 690410.
• Obar RA, Dingus J, Bayley H, Vallee RB (Nov 1989). "The RII subunit of cAMP-dependent protein kinase binds to a common amino-terminal domain in microtubule-associated proteins 2A, 2B, and 2C". Neuron. 3 (5): 639–45. doi:10.1016/0896-6273(89)90274-2. PMID 2561973. S2CID 1329548.
• Rubino HM, Dammerman M, Shafit-Zagardo B, Erlichman J (Nov 1989). "Localization and characterization of the binding site for the regulatory subunit of type II cAMP-dependent protein kinase on MAP2". Neuron. 3 (5): 631–8. doi:10.1016/0896-6273(89)90273-0. PMID 2701845. S2CID 45499202.
• Hemmings BA, Aitken A, Cohen P, Rymond M, Hofmann F (Oct 1982). "Phosphorylation of the type-II regulatory subunit of cyclic-AMP-dependent protein kinase by glycogen synthase kinase 3 and glycogen synthase kinase 5". European Journal of Biochemistry. 127 (3): 473–81. doi:10.1111/j.1432-1033.1982.tb06896.x. PMID 6293815.
• Hofmann B, Nishanian P, Nguyen T, Insixiengmay P, Fahey JL (Jul 1993). "Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 90 (14): 6676–80. Bibcode:1993PNAS...90.6676H. doi:10.1073/pnas.90.14.6676. PMC 46995. PMID 7688126.
• Pariset C, Weinman S (Dec 1994). "Differential localization of two isoforms of the regulatory subunit RII alpha of cAMP-dependent protein kinase in human sperm: biochemical and cytochemical study". Molecular Reproduction and Development. 39 (4): 415–22. doi:10.1002/mrd.1080390410. PMID 7893490. S2CID 36203256.
• Cheley S, Panchal RG, Carr DW, Scott JD, Bayley H (Jan 1994). "Type II regulatory subunits of cAMP-dependent protein kinase and their binding proteins in the nervous system of Aplysia californica". The Journal of Biological Chemistry. 269 (4): 2911–20. doi:10.1016/S0021-9258(17)42028-X. PMID 7905481.
• Hausken ZE, Coghlan VM, Hastings CA, Reimann EM, Scott JD (Sep 1994). "Type II regulatory subunit (RII) of the cAMP-dependent protein kinase interaction with A-kinase anchor proteins requires isoleucines 3 and 5". The Journal of Biological Chemistry. 269 (39): 24245–51. doi:10.1016/S0021-9258(19)51074-2. PMID 7929081.
• Hofmann B, Nishanian P, Fan J, Nguyen T, Fahey JL (Jul 1994). "HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro". AIDS. 8 (7): 1016–7. doi:10.1097/00002030-199407000-00025. PMID 7946090.
• Beebe SJ, Salomonsky P, Holroyd C, Becker D (Dec 1993). "Differential expression of cyclic AMP-dependent protein kinase isozymes in normal human melanocytes and malignant melanomas". Cell Growth & Differentiation. 4 (12): 1005–12. PMID 8117614.
• Coghlan VM, Langeberg LK, Fernandez A, Lamb NJ, Scott JD (Mar 1994). "Cloning and characterization of AKAP 95, a nuclear protein that associates with the regulatory subunit of type II cAMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (10): 7658–65. doi:10.1016/S0021-9258(17)37338-6. PMID 8125992.
• Lester LB, Coghlan VM, Nauert B, Scott JD (Apr 1996). "Cloning and characterization of a novel A-kinase anchoring protein. AKAP 220, association with testicular peroxisomes". The Journal of Biological Chemistry. 271 (16): 9460–5. doi:10.1074/jbc.271.16.9460. PMID 8621616.
• Foss KB, Solberg R, Simard J, Myklebust F, Hansson V, Jahnsen T, Taskén K (Jan 1997). "Molecular cloning, upstream sequence and promoter studies of the human gene for the regulatory subunit RII alpha of cAMP-dependent protein kinase". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1350 (1): 98–108. doi:10.1016/S0167-4781(96)00152-2. PMID 9003463.
• Dransfield DT, Bradford AJ, Smith J, Martin M, Roy C, Mangeat PH, Goldenring JR (Jan 1997). "Ezrin is a cyclic AMP-dependent protein kinase anchoring protein". The EMBO Journal. 16 (1): 35–43. doi:10.1093/emboj/16.1.35. PMC 1169611. PMID 9009265.