PRKAR1A

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.{{cite web | title = Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573}}

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.

Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.{{Citation needed|date=December 2007}}

PRKAR1A has been shown to interact with:

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• AKAP10,{{cite journal | vauthors = Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS | title = D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 21 | pages = 11184–9 | date = October 1997 | pmid = 9326583 | pmc = 23409 | doi = 10.1073/pnas.94.21.11184| bibcode = 1997PNAS...9411184J | doi-access = free }}{{cite journal | vauthors = 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 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
• AKAP1,{{cite journal | vauthors = Carlson CR, Ruppelt A, Taskén K | title = 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 | journal = J. Mol. Biol. | volume = 327 | issue = 3 | pages = 609–18 | date = March 2003 | pmid = 12634056 | doi = 10.1016/s0022-2836(03)00093-7}}{{cite journal | vauthors = Herberg FW, Maleszka A, Eide T, Vossebein L, Tasken K | title = Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding | journal = J. Mol. Biol. | volume = 298 | issue = 2 | pages = 329–39 | date = April 2000 | pmid = 10764601 | doi = 10.1006/jmbi.2000.3662 }}
• AKAP4,{{cite journal | vauthors = Brown PR, Miki K, Harper DB, Eddy EM | title = A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum | journal = Biol. Reprod. | volume = 68 | issue = 6 | pages = 2241–8 | date = June 2003 | pmid = 12606363 | doi = 10.1095/biolreprod.102.013466 | doi-access = free }}{{cite journal | vauthors = Miki K, Eddy EM | title = Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1 | journal = J. Biol. Chem. | volume = 273 | issue = 51 | pages = 34384–90 | date = December 1998 | pmid = 9852104 | doi = 10.1074/jbc.273.51.34384| doi-access = free }}
• ARFGEF1,{{cite journal | vauthors = Li H, Adamik R, Pacheco-Rodriguez G, Moss J, Vaughan M | title = Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 4 | pages = 1627–32 | date = February 2003 | pmid = 12571360 | pmc = 149883 | doi = 10.1073/pnas.0337678100 | bibcode = 2003PNAS..100.1627L | doi-access = free }}
• ARFGEF2,
• Grb2,{{cite journal | vauthors = Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L, Pelicci PG, Ciardiello F | title = The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor | journal = Oncogene | volume = 14 | issue = 8 | pages = 923–8 | date = February 1997 | pmid = 9050991 | doi = 10.1038/sj.onc.1200906 | s2cid = 10640461 | doi-access = }}
• MYO7A,{{cite journal | vauthors = Küssel-Andermann P, El-Amraoui A, Safieddine S, Hardelin JP, Nouaille S, Camonis J, Petit C | title = Unconventional myosin VIIA is a novel A-kinase-anchoring protein | journal = J. Biol. Chem. | volume = 275 | issue = 38 | pages = 29654–9 | date = September 2000 | pmid = 10889203 | doi = 10.1074/jbc.M004393200 | doi-access = free }}
• PRKAR1B,{{cite journal | vauthors = Taskén K, Skålhegg BS, Solberg R, Andersson KB, Taylor SS, Lea T, Blomhoff HK, Jahnsen T, Hansson V | title = Novel isozymes of cAMP-dependent protein kinase exist in human cells due to formation of RI alpha-RI beta heterodimeric complexes | journal = J. Biol. Chem. | volume = 268 | issue = 28 | pages = 21276–83 | date = October 1993 | doi = 10.1016/S0021-9258(19)36921-2 | pmid = 8407966 | doi-access = free }} and
• UBE2M.{{cite journal | vauthors = 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 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Mol. Syst. Biol. | volume = 3 | pages = 89 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 | year = 2007 }}

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• cAMP-dependent protein kinase

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• [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P10644 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)

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Category:Signal transduction