PRKAR1A

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Protein kinase, cAMP-dependent, regulatory, type I, alpha
Protein PRKAR1A PDB 1ne4.png
PDB rendering based on 1ne4.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PRKAR1A ; ACRDYS1; ADOHR; CAR; CNC; CNC1; PKR1; PPNAD1; PRKAR1; TSE1
External IDs OMIM188830 MGI104878 HomoloGene37664 ChEMBL: 4928 GeneCards: PRKAR1A Gene
EC number 2.7.11.1
RNA expression pattern
PBB GE PRKAR1A 200603 at tn.png
PBB GE PRKAR1A 200604 s at tn.png
PBB GE PRKAR1A 200605 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5573 19084
Ensembl ENSG00000108946 ENSMUSG00000020612
UniProt P10644 Q9DBC7
RefSeq (mRNA) NM_001276289 NM_021880
RefSeq (protein) NP_001263218 NP_068680
Location (UCSC) Chr 17:
66.41 – 66.55 Mb
Chr 11:
109.65 – 109.67 Mb
PubMed search [1] [2]

cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene.[1]

Function[edit]

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.[2]

Clinical significance[edit]

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.[2]

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

Interactions[edit]

PRKAR1A has been shown to interact with AKAP1,[3][4] AKAP10,[5][6] ARFGEF1,[7] ARFGEF2,[7] UBE2M,[8] AKAP4,[9][10] Grb2,[11] PRKAR1B[3][12] and MYO7A.[13]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ a b "Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)". 
  3. ^ a b Carlson, Cathrine R; Ruppelt Anja, Taskén Kjetil (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. (England) 327 (3): 609–18. doi:10.1016/S0022-2836(03)00093-7. ISSN 0022-2836. PMID 12634056. 
  4. ^ Herberg, F W; 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. (ENGLAND) 298 (2): 329–39. doi:10.1006/jmbi.2000.3662. ISSN 0022-2836. PMID 10764601. 
  5. ^ Huang, L J; Durick K, Weiner J A, Chun J, Taylor S S (October 1997). "D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (21): 11184–9. doi:10.1073/pnas.94.21.11184. ISSN 0027-8424. PMC 23409. PMID 9326583. 
  6. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  7. ^ a b Li, Hewang; Adamik Ronald, Pacheco-Rodriguez Gustavo, Moss Joel, Vaughan Martha (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. (United States) 100 (4): 1627–32. doi:10.1073/pnas.0337678100. ISSN 0027-8424. PMC 149883. PMID 12571360. 
  8. ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. 
  9. ^ Brown, Paula R; Miki Kiyoshi, Harper Deborah B, Eddy Edward M (June 2003). "A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum". Biol. Reprod. (United States) 68 (6): 2241–8. doi:10.1095/biolreprod.102.013466. ISSN 0006-3363. PMID 12606363. 
  10. ^ Miki, K; Eddy E M (December 1998). "Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1". J. Biol. Chem. (UNITED STATES) 273 (51): 34384–90. doi:10.1074/jbc.273.51.34384. ISSN 0021-9258. PMID 9852104. 
  11. ^ Tortora, G; Damiano V, Bianco C, Baldassarre G, Bianco A R, Lanfrancone L, Pelicci P G, 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 (ENGLAND) 14 (8): 923–8. doi:10.1038/sj.onc.1200906. ISSN 0950-9232. PMID 9050991. 
  12. ^ Taskén, K; Skålhegg B S, Solberg R, Andersson K B, Taylor S S, Lea T, Blomhoff H K, 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. (UNITED STATES) 268 (28): 21276–83. ISSN 0021-9258. PMID 8407966. 
  13. ^ Küssel-Andermann, P; El-Amraoui A, Safieddine S, Hardelin J P, Nouaille S, Camonis J, Petit C (September 2000). "Unconventional myosin VIIA is a novel A-kinase-anchoring protein". J. Biol. Chem. (UNITED STATES) 275 (38): 29654–9. doi:10.1074/jbc.M004393200. ISSN 0021-9258. PMID 10889203. 

Further reading[edit]

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