PRKAR1A

PRKAR1A
Identifiers
Aliases	PRKAR1A , ACRDYS1, ADOHR, CAR, CNC, CNC1, PKR1, PPNAD1, PRKAR1, TSE1, protein kinase cAMP-dependent type I regulatory subunit alpha
External IDs	OMIM: 188830; MGI: 104878; HomoloGene: 37664; GeneCards: PRKAR1A; OMA:PRKAR1A - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q24.2 Start 68,511,780 bp [1] End 68,551,319 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 E1|11 72.33 cM Start 109,540,231 bp [2] End 109,560,482 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of paranasal sinus germinal epithelium lateral nuclear group of thalamus bronchial epithelial cell epithelium of nasopharynx Epithelium of choroid plexus superficial temporal artery Pars compacta pars reticulata caput epididymis Top expressed in arcuate nucleus ventral tegmental area dorsomedial hypothalamic nucleus paraventricular nucleus of hypothalamus median eminence cingulate gyrus ventromedial nucleus mammillary body subiculum anterior amygdaloid area 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 kinase activity Cellular component cytoplasm cytosol membrane plasma membrane raft neuromuscular junction plasma membrane ciliary base nucleotide-activated protein kinase complex immunological synapse cAMP-dependent protein kinase complex axoneme protein-containing complex synapse glutamatergic synapse Biological process regulation of protein phosphorylation activation of protein kinase A activity intracellular signal transduction negative regulation of protein kinase activity regulation of transcription by RNA polymerase II cellular response to glucagon stimulus mesoderm formation blood coagulation female meiotic nuclear division negative regulation of meiotic nuclear division cardiac muscle cell proliferation negative regulation of cAMP-dependent protein kinase activity negative regulation of activated T cell proliferation heart development renal water homeostasis regulation of protein kinase activity sarcomere organization cGMP-mediated signaling phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5573 19084 Ensembl ENSG00000108946 ENSMUSG00000020612 UniProt P10644 Q9DBC7 RefSeq (mRNA) NM_001276289 NM_001276290 NM_001278433 NM_002734 NM_212471 NM_212472 NM_001369389 NM_001369390 NM_021880 NM_001313973 NM_001313974 NM_001313975 NM_001313976 NM_001362677 NM_001373912 NM_001373913 RefSeq (protein) NP_001263218 NP_001263219 NP_001265362 NP_002725 NP_997636 NP_997637 NP_001356318 NP_001356319 NP_001263218.1 NP_001265362.1 NP_002725.1 NP_997636.1 NP_997637.1 NP_001300902 NP_001300903 NP_001300904 NP_001300905 NP_068680 NP_001349606 NP_001360841 NP_001360842 Location (UCSC) Chr 17: 68.51 – 68.55 Mb Chr 11: 109.54 – 109.56 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene. ^[5]

Function

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent 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 protein was found to be a tissue-specific extinguisher that downregulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed. ^[6]

Clinical significance

Functional null mutations in this gene cause Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome. This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. ^[6]

Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.^{[ citation needed ]}

Interactions

PRKAR1A has been shown to interact with:

• AKAP10, ^{[7] [8]}
• AKAP1, ^{[9] [10]}
• AKAP4, ^{[11] [12]}
• ARFGEF1, ^[13]
• ARFGEF2, ^[13]
• Grb2, ^[14]
• MYO7A, ^[15]
• PRKAR1B, ^{[9] [16]} and
• UBE2M. ^[17]

See also

• cAMP-dependent protein kinase

References

1. GRCh38: Ensembl release 89: ENSG00000108946 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020612 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Scambler P, Oyen O, Wainwright B, Farrall M, Law HY, Estivill X, Sandberg M, Williamson R, Jahnsen T (December 1987). "Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis". Am J Hum Genet. 41 (5): 925–32. PMC   1684338 . PMID   3479018.
6. "Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)".
7. Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS (October 1997). "D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11184–9. Bibcode:1997PNAS...9411184J. doi: 10.1073/pnas.94.21.11184 . PMC   23409 . PMID   9326583.
8. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
9. Carlson CR, Ruppelt A, Taskén K (March 2003). "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase a in vivo by the yeast two hybrid system". J. Mol. Biol. 327 (3): 609–18. doi:10.1016/s0022-2836(03)00093-7. PMID   12634056.
10. Herberg FW, Maleszka A, Eide T, Vossebein L, Tasken K (April 2000). "Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding". J. Mol. Biol. 298 (2): 329–39. doi:10.1006/jmbi.2000.3662. PMID   10764601.
11. Brown PR, Miki K, Harper DB, Eddy EM (June 2003). "A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum". Biol. Reprod. 68 (6): 2241–8. doi: 10.1095/biolreprod.102.013466 . PMID   12606363.
12. Miki K, Eddy EM (December 1998). "Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1". J. Biol. Chem. 273 (51): 34384–90. doi: 10.1074/jbc.273.51.34384 . PMID   9852104.
13. Li H, Adamik R, Pacheco-Rodriguez G, Moss J, Vaughan M (February 2003). "Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2)". Proc. Natl. Acad. Sci. U.S.A. 100 (4): 1627–32. Bibcode:2003PNAS..100.1627L. doi: 10.1073/pnas.0337678100 . PMC   149883 . PMID   12571360.
14. Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L, Pelicci PG, Ciardiello F (February 1997). "The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor". Oncogene. 14 (8): 923–8. doi:10.1038/sj.onc.1200906. PMID   9050991. S2CID   10640461.
15. Küssel-Andermann P, El-Amraoui A, Safieddine S, Hardelin JP, Nouaille S, Camonis J, Petit C (September 2000). "Unconventional myosin VIIA is a novel A-kinase-anchoring protein". J. Biol. Chem. 275 (38): 29654–9. doi: 10.1074/jbc.M004393200 . PMID   10889203.
16. Taskén K, Skålhegg BS, Solberg R, Andersson KB, Taylor SS, Lea T, Blomhoff HK, Jahnsen T, Hansson V (October 1993). "Novel isozymes of cAMP-dependent protein kinase exist in human cells due to formation of RI alpha-RI beta heterodimeric complexes". J. Biol. Chem. 268 (28): 21276–83. doi: 10.1016/S0021-9258(19)36921-2 . PMID   8407966.
17. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.

Further reading

• Stratakis CA (2002). "Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit (PRKAR1A) in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas" (Carney complex)". Ann. N. Y. Acad. Sci. 968 (1): 3–21. Bibcode:2002NYASA.968....3S. doi:10.1111/j.1749-6632.2002.tb04323.x. PMID   12119264. S2CID   26108486.
• Bourdeau I, Stratakis CA (2002). "Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease". Ann. N. Y. Acad. Sci. 968 (1): 240–55. Bibcode:2002NYASA.968..240B. doi:10.1111/j.1749-6632.2002.tb04339.x. PMID   12119280. S2CID   22397904.
• Alto N, Carlisle Michel JJ, Dodge KL, Langeberg LK, Scott JD (2003). "Intracellular targeting of protein kinases and phosphatases". Diabetes. 51 (Suppl 3): S385–8. doi: 10.2337/diabetes.51.2007.s385 . PMID   12475780.
• Stergiopoulos SG, Stratakis CA (2003). "Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease!". FEBS Lett. 546 (1): 59–64. doi:10.1016/S0014-5793(03)00452-6. PMID   12829237. S2CID   37055425.
• Bossis I, Stratakis CA (2004). "Minireview: PRKAR1A: normal and abnormal functions". Endocrinology. 145 (12): 5452–8. doi: 10.1210/en.2004-0900 . PMID   15331577.
• Cho-Chung YS, Nesterova MV (2006). "Tumor reversion: protein kinase A isozyme switching". Ann. N. Y. Acad. Sci. 1058: 76–86. doi:10.1196/annals.1359.014. PMID   16394127. S2CID   45471438.
• Lytras A, Tolis G (2006). "Growth hormone-secreting tumors: genetic aspects and data from animal models". Neuroendocrinology. 83 (3–4): 166–78. doi:10.1159/000095525. PMID   17047380. S2CID   45606794.
• Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L (2007). "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets. 7 (12): 1595–606. doi:10.2174/138945006779025338. PMID   17168834.
• Boshart M, Weih F, Nichols M, Schütz G (1991). "The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase" (PDF). Cell. 66 (5): 849–59. doi:10.1016/0092-8674(91)90432-X. PMID   1832337. S2CID   8277752.
• Jones KW, Shapero MH, Chevrette M, Fournier RE (1991). "Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A". Cell. 66 (5): 861–72. doi:10.1016/0092-8674(91)90433-Y. PMID   1889088. S2CID   24273073.
• Hofmann B, Nishanian P, Baldwin RL, Insixiengmay P, Nel A, Fahey JL (1991). "HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism". J. Immunol. 145 (11): 3699–705. doi: 10.4049/jimmunol.145.11.3699 . PMID   1978848.
• Sandberg M, Skålhegg B, Jahnsen T (1990). "The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals". Biochem. Biophys. Res. Commun. 167 (1): 323–30. doi:10.1016/0006-291X(90)91768-N. PMID   2310396.
• Lem J, Chin AC, Thayer MJ, Leach RJ, Fournier RE (1988). "Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1". Proc. Natl. Acad. Sci. U.S.A. 85 (19): 7302–6. Bibcode:1988PNAS...85.7302L. doi: 10.1073/pnas.85.19.7302 . PMC   282174 . PMID   2902627.
• Sandberg M, Taskén K, Oyen O, Hansson V, Jahnsen T (1988). "Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis". Biochem. Biophys. Res. Commun. 149 (3): 939–45. doi:10.1016/0006-291X(87)90499-2. PMID   3426618.
• Geahlen RL, Carmichael DF, Hashimoto E, Krebs EG (1982). "Phosphorylation of cAMP-dependent protein kinase subunits". Adv. Enzyme Regul. 20: 195–209. doi:10.1016/0065-2571(82)90016-4. PMID   6287816.
• Guild BC, Strominger JL (1984). "HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of phosphorylation and segmentation in class i major histocompatibility complex gene structure". J. Biol. Chem. 259 (21): 13504–10. doi: 10.1016/S0021-9258(18)90722-2 . PMID   6333425.
• Bongarzone I, Monzini N, Borrello MG, Carcano C, Ferraresi G, Arighi E, Mondellini P, Della Porta G, Pierotti MA (1993). "Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A". Mol. Cell. Biol. 13 (1): 358–66. doi:10.1128/MCB.13.1.358. PMC   358915 . PMID   7678053.
• Hofmann B, Nishanian P, Nguyen T, Insixiengmay P, Fahey JL (1993). "Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6676–80. Bibcode:1993PNAS...90.6676H. doi: 10.1073/pnas.90.14.6676 . PMC   46995 . PMID   7688126.
• Hofmann B, Nishanian P, Fan J, Nguyen T, Fahey JL (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.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.