PRKAR1A

Identifiers

PRKAR1A, ACRDYS1, ADOHR, CAR, CNC, CNC1, PKR1, PPNAD1, PRKAR1, TSE1, protein kinase cAMP-dependent type I regulatory subunit alpha

External IDs

MGI: 104878 HomoloGene: 37664 GeneCards: PRKAR1A

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 • kinase activity
Cellular component	• cytoplasm • cytosol • membrane • plasma membrane raft • neuromuscular junction • plasma membrane • protein complex • ciliary base • nucleotide-activated protein kinase complex • immunological synapse • cAMP-dependent protein kinase complex
Biological process	• regulation of protein phosphorylation • activation of protein kinase A activity • intracellular signal transduction • negative regulation of protein kinase activity • regulation of transcription from RNA polymerase II promoter • cellular response to glucagon stimulus • mesoderm formation • blood coagulation • female meiotic 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 • phosphorylation
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

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_021880 NM_001313973 NM_001313974 NM_001313975 NM_001313976

RefSeq (protein)

NP_001263218.1 NP_001263219.1 NP_001265362.1 NP_002725.1 NP_997636.1
NP_997637.1 NP_001263218.1 NP_001265362.1 NP_002725.1 NP_997636.1 NP_997637.1


NP_001300902.1 NP_001300903.1 NP_001300904.1 NP_001300905.1 NP_068680.1

Location (UCSC)

Chr 17: 68.51 – 68.55 Mb

Chr 11: 109.65 – 109.67 Mb

PubMed search

^[1]

^[2]

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.^[3]

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 down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed.^[4]

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.^[4]

Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.

Interactions

PRKAR1A has been shown to interact with:

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
1 2 "Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)".
↑ 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. doi:10.1073/pnas.94.21.11184. PMC 23409. PMID 9326583.
↑ 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. doi:10.1038/nature04209. PMID 16189514.
1 2 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.
↑ 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.
↑ 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.
↑ 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.
1 2 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. doi:10.1073/pnas.0337678100. PMC 149883. PMID 12571360.
↑ 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.
↑ 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.
↑ 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. PMID 8407966.
↑ 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. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

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: 3–21. doi:10.1111/j.1749-6632.2002.tb04323.x. PMID 12119264.
Bourdeau I, Stratakis CA (2002). "Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease". Ann. N. Y. Acad. Sci. 968: 240–55. doi:10.1111/j.1749-6632.2002.tb04339.x. PMID 12119280.
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.
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.
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.
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". Cell. 66 (5): 849–59. doi:10.1016/0092-8674(91)90432-X. PMID 1832337.
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.
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. 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. 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. 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. 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. 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.

PDB gallery

1ne4: Crystal Structure of Rp-cAMP Binding R1a Subunit of cAMP-dependent Protein Kinase

1ne6: Crystal structure of Sp-cAMP binding R1a subunit of cAMP-dependent protein kinase

1rgs: REGULATORY SUBUNIT OF CAMP DEPENDENT PROTEIN KINASE

1rl3: Crystal structure of cAMP-free R1a subunit of PKA

2ezw: Solution structure of the docking and dimerization domain of the type I alpha regulatory subunit of protein kinase A (RIalpha D/D)

Intracellular signaling peptides and proteins

MAP

see MAP kinase pathway

Calcium

G protein

Heterotrimeric

cAMP:	Heterotrimeric G protein Gs/Gi Adenylate cyclase cAMP 3',5'-cyclic-AMP phosphodiesterase Protein kinase A

cGMP:	Transducin Gustducin Guanylate cyclase cGMP 3',5'-cyclic-GMP phosphodiesterase Protein kinase G

G alpha subunit G_α GNAO1 GNAI1 GNAI2 GNAI3 GNAT1 GNAT2 GNAT3 GNAZ GNAS GNAL GNAQ GNA11 GNA12 GNA13 GNA14 GNA15/GNA16

G beta-gamma complex G_β GNB1 GNB2 GNB3 GNB4 GNB5 G_γ GNGT1 GNGT2 GNG2 GNG3 GNG4 GNG5 GNG7 GNG8 GNG10 GNG11 GNG12 GNG13 BSCL2

G protein-coupled receptor kinase AMP-activated protein kinase

Monomeric

Cyclin

Lipid

Other protein kinase

Serine/threonine:	Casein kinase 1 2 eIF-2 kinase EIF2AK3 Glycogen synthase kinase GSK1 GSK2 GSK-3 GSK3A GSK3B IκB kinase CHUK IKK2 IKBKG Interleukin-1 receptor-associated kinase IRAK1 IRAK2 IRAK3 IRAK4 Lim kinase LIMK1 LIMK2 p21-activated kinases PAK1 PAK2 PAK3 PAK4 Rho-associated protein kinase ROCK1 ROCK2 Ribosomal s6 kinase RPS6KA1

Tyrosine:	ZAP70 Focal adhesion protein-tyrosine kinase PTK2 PTK2B BTK

both	Dual-specificity kinase

Other protein phosphatase

Serine/threonine:	Protein phosphatase 2

Tyrosine:	protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase Sh2 domain-containing protein tyrosine phosphatase

both:	Dual-specificity phosphatase

Apoptosis

see apoptosis signaling pathway

GTP-binding protein regulators

see GTP-binding protein regulators

Other

see also deficiencies of intracellular signaling peptides and proteins

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

This article is issued from Wikipedia - version of the 5/20/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

PRKAR1A

Function

Clinical significance

Interactions

See also

References

Further reading