cAMP-dependent protein kinase type I-alpha regulatory subunit

Details

Name
cAMP-dependent protein kinase type I-alpha regulatory subunit
Synonyms
  • PKR1
  • PRKAR1
  • Tissue-specific extinguisher 1
  • TSE1
Gene Name
PRKAR1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006682|cAMP-dependent protein kinase type I-alpha regulatory subunit
MESGSTAASEEARSLRECELYVQKHNIQALLKDSIVQLCTARPERPMAFLREYFERLEKE
EAKQIQNLQKAGTRTDSREDEISPPPPNPVVKGRRRRGAISAEVYTEEDAASYVRKVIPK
DYKTMAALAKAIEKNVLFSHLDDNERSDIFDAMFSVSFIAGETVIQQGDEGDNFYVIDQG
ETDVYVNNEWATSVGEGGSFGELALIYGTPRAATVKAKTNVKLWGIDRDSYRRILMGSTL
RKRKMYEEFLSKVSILESLDKWERLTVADALEPVQFEDGQKIVVQGEPGDEFFIILEGSA
AVLQRRSENEEFVEVGRLGPSDYFGEIALLMNRPRAATVVARGPLKCVKLDRPRFERVLG
PCSDILKRNIQQYNSFVSLSV
Number of residues
381
Molecular Weight
42981.28
Theoretical pI
5.0
GO Classification
Functions
cAMP binding / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase regulator activity / protein kinase A catalytic subunit binding / ubiquitin protein ligase binding
Processes
activation of phospholipase C activity / activation of protein kinase A activity / blood coagulation / cardiac muscle cell proliferation / cellular response to glucagon stimulus / energy reserve metabolic process / epidermal growth factor receptor signaling pathway / female meiotic division / fibroblast growth factor receptor signaling pathway / innate immune response / intracellular signal transduction / mesoderm formation / negative regulation of activated T cell proliferation / negative regulation of cAMP-dependent protein kinase activity / negative regulation of meiotic nuclear division / neurotrophin TRK receptor signaling pathway / regulation of insulin secretion / regulation of transcription from RNA polymerase II promoter / renal water homeostasis / sarcomere organization / signal transduction / small molecule metabolic process / transmembrane transport / water transport
Components
cAMP-dependent protein kinase complex / ciliary base / cytoplasm / cytosol / membrane / neuromuscular junction / nucleotide-activated protein kinase complex / plasma membrane raft / protein complex
General Function
Ubiquitin protein ligase binding
Specific Function
Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0017096|cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)
ATGGAGTCTGGCAGTACCGCCGCCAGTGAGGAGGCACGCAGCCTTCGAGAATGTGAGCTC
TACGTCCAGAAGCATAACATTCAAGCGCTGCTCAAAGATTCTATTGTGCAGTTGTGCACT
GCTCGACCTGAGAGACCCATGGCATTCCTCAGGGAATACTTTGAGAGGTTGGAGAAGGAG
GAGGCAAAACAGATTCAGAATCTGCAGAAAGCAGGCACTCGTACAGACTCAAGGGAGGAT
GAGATTTCTCCTCCTCCACCCAACCCAGTGGTTAAAGGTAGGAGGCGACGAGGTGCTATC
AGCGCTGAGGTCTACACGGAGGAAGATGCGGCATCCTATGTTAGAAAGGTTATACCAAAA
GATTACAAGACAATGGCCGCTTTAGCCAAAGCCATTGAAAAGAATGTGCTGTTTTCACAT
CTTGATGATAATGAGAGAAGTGATATTTTTGATGCCATGTTTTCGGTCTCCTTTATCGCA
GGAGAGACTGTGATTCAGCAAGGTGATGAAGGGGATAACTTCTATGTGATTGATCAAGGA
GAGACGGATGTCTATGTTAACAATGAATGGGCAACCAGTGTTGGGGAAGGAGGGAGCTTT
GGAGAACTTGCTTTGATTTATGGAACACCGAGAGCAGCCACTGTCAAAGCAAAGACAAAT
GTGAAATTGTGGGGCATCGACCGAGACAGCTATAGAAGAATCCTCATGGGAAGCACACTG
AGAAAGCGGAAGATGTATGAGGAATTCCTTAGTAAAGTCTCTATTTTAGAGTCTCTGGAC
AAGTGGGAACGTCTTACGGTAGCTGATGCATTGGAACCAGTGCAGTTTGAAGATGGGCAG
AAGATTGTGGTGCAGGGAGAACCAGGGGATGAGTTCTTCATTATTTTAGAGGGGTCAGCT
GCTGTGCTACAACGTCGGTCAGAAAATGAAGAGTTTGTTGAAGTGGGAAGATTGGGGCCT
TCTGATTATTTTGGTGAAATTGCACTACTGATGAATCGTCCTCGTGCTGCCACAGTTGTT
GCTCGTGGCCCCTTGAAGTGCGTTAAGCTGGACCGACCTAGATTTGAACGTGTTCTTGGC
CCATGCTCAGACATCCTCAAACGAAACATCCAGCAGTACAACAGTTTTGTGTCACTGTCT
GTCTGA
Chromosome Location
17
Locus
17q23-q24
External Identifiers
ResourceLink
UniProtKB IDP10644
UniProtKB Entry NameKAP0_HUMAN
GenBank Gene IDM18468
GenAtlas IDPRKAR1A
HGNC IDHGNC:9388
General References
  1. Sandberg M, Tasken K, Oyen O, Hansson V, Jahnsen T: 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. 1987 Dec 31;149(3):939-45. [PubMed:3426618]
  2. Sandberg M, Skalhegg B, Jahnsen T: 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. 1990 Feb 28;167(1):323-30. [PubMed:2310396]
  3. Jones KW, Shapero MH, Chevrette M, Fournier RE: Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A. Cell. 1991 Sep 6;66(5):861-72. [PubMed:1889088]
  4. Solberg R, Sandberg M, Natarajan V, Torjesen PA, Hansson V, Jahnsen T, Tasken K: The human gene for the regulatory subunit RI alpha of cyclic adenosine 3', 5'-monophosphate-dependent protein kinase: two distinct promoters provide differential regulation of alternately spliced messenger ribonucleic acids. Endocrinology. 1997 Jan;138(1):169-81. [PubMed:8977401]
  5. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [PubMed:16625196]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801]
  8. Groussin L, Jullian E, Perlemoine K, Louvel A, Leheup B, Luton JP, Bertagna X, Bertherat J: Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease. J Clin Endocrinol Metab. 2002 Sep;87(9):4324-9. [PubMed:12213893]
  9. Gupte RS, Weng Y, Liu L, Lee MY: The second subunit of the replication factor C complex (RFC40) and the regulatory subunit (RIalpha) of protein kinase A form a protein complex promoting cell survival. Cell Cycle. 2005 Feb;4(2):323-9. Epub 2005 Feb 13. [PubMed:15655353]
  10. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  11. Glesne D, Huberman E: Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. Oncogene. 2006 Jul 6;25(29):4086-98. Epub 2006 Feb 20. [PubMed:16491121]
  12. Pasqualucci L, Kitaura Y, Gu H, Dalla-Favera R: PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells. Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):395-400. Epub 2005 Dec 30. [PubMed:16387847]
  13. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [PubMed:19367720]
  14. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087]
  15. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976]
  16. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  17. Han G, Ye M, Zhou H, Jiang X, Feng S, Jiang X, Tian R, Wan D, Zou H, Gu J: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics. 2008 Apr;8(7):1346-61. doi: 10.1002/pmic.200700884. [PubMed:18318008]
  18. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330]
  19. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  20. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  21. Santos NC, Kim KH: Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar 9. [PubMed:20215566]
  22. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  23. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  24. Linglart A, Menguy C, Couvineau A, Auzan C, Gunes Y, Cancel M, Motte E, Pinto G, Chanson P, Bougneres P, Clauser E, Silve C: Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance. N Engl J Med. 2011 Jun 9;364(23):2218-26. doi: 10.1056/NEJMoa1012717. [PubMed:21651393]
  25. Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, Feliciello A: Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol. 2011 Apr;13(4):412-22. doi: 10.1038/ncb2209. Epub 2011 Mar 20. [PubMed:21423175]
  26. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692]
  27. Tung SC, Hwang DY, Yang JW, Chen WJ, Lee CT: An unusual presentation of Carney complex with diffuse primary pigmented nodular adrenocortical disease on one adrenal gland and a nonpigmented adrenocortical adenoma and focal primary pigmented nodular adrenocortical disease on the other. Endocr J. 2012;59(9):823-30. Epub 2012 Jun 20. [PubMed:22785148]
  28. Burgers PP, Ma Y, Margarucci L, Mackey M, van der Heyden MA, Ellisman M, Scholten A, Taylor SS, Heck AJ: A small novel A-kinase anchoring protein (AKAP) that localizes specifically protein kinase A-regulatory subunit I (PKA-RI) to the plasma membrane. J Biol Chem. 2012 Dec 21;287(52):43789-97. doi: 10.1074/jbc.M112.395970. Epub 2012 Oct 31. [PubMed:23115245]
  29. Park KU, Kim HS, Lee SK, Jung WW, Park YK: Novel Mutation in PRKAR1A in Carney Complex. Korean J Pathol. 2012 Dec;46(6):595-600. doi: 10.4132/KoreanJPathol.2012.46.6.595. Epub 2012 Dec 26. [PubMed:23323113]
  30. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [PubMed:22223895]
  31. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [PubMed:22814378]
  32. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  33. Veugelers M, Wilkes D, Burton K, McDermott DA, Song Y, Goldstein MM, La Perle K, Vaughan CJ, O'Hagan A, Bennett KR, Meyer BJ, Legius E, Karttunen M, Norio R, Kaariainen H, Lavyne M, Neau JP, Richter G, Kirali K, Farnsworth A, Stapleton K, Morelli P, Takanashi Y, Bamforth JS, Eitelberger F, Noszian I, Manfroi W, Powers J, Mochizuki Y, Imai T, Ko GT, Driscoll DA, Goldmuntz E, Edelberg JM, Collins A, Eccles D, Irvine AD, McKnight GS, Basson CT: Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice. Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14222-7. Epub 2004 Sep 15. [PubMed:15371594]
  34. Greene EL, Horvath AD, Nesterova M, Giatzakis C, Bossis I, Stratakis CA: In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat. 2008 May;29(5):633-9. doi: 10.1002/humu.20688. [PubMed:18241045]
  35. Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, Guerrot AM, Flahaut P, Duncombe A, Baujat G, Lyonnet S, Thalassinos C, Nitschke P, Casanova JL, Le Merrer M, Munnich A, Cormier-Daire V: Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):740-5. doi: 10.1016/j.ajhg.2012.03.003. Epub 2012 Mar 29. [PubMed:22464250]
  36. Lee H, Graham JM Jr, Rimoin DL, Lachman RS, Krejci P, Tompson SW, Nelson SF, Krakow D, Cohn DH: Exome sequencing identifies PDE4D mutations in acrodysostosis. Am J Hum Genet. 2012 Apr 6;90(4):746-51. doi: 10.1016/j.ajhg.2012.03.004. Epub 2012 Mar 29. [PubMed:22464252]
  37. Linglart A, Fryssira H, Hiort O, Holterhus PM, Perez de Nanclares G, Argente J, Heinrichs C, Kuechler A, Mantovani G, Leheup B, Wicart P, Chassot V, Schmidt D, Rubio-Cabezas O, Richter-Unruh A, Berrade S, Pereda A, Boros E, Munoz-Calvo MT, Castori M, Gunes Y, Bertrand G, Bougneres P, Clauser E, Silve C: PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance. J Clin Endocrinol Metab. 2012 Dec;97(12):E2328-38. doi: 10.1210/jc.2012-2326. Epub 2012 Oct 5. [PubMed:23043190]
  38. Nagasaki K, Iida T, Sato H, Ogawa Y, Kikuchi T, Saitoh A, Ogata T, Fukami M: PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance. J Clin Endocrinol Metab. 2012 Sep;97(9):E1808-13. doi: 10.1210/jc.2012-1369. Epub 2012 Jun 20. [PubMed:22723333]
  39. Muhn F, Klopocki E, Graul-Neumann L, Uhrig S, Colley A, Castori M, Lankes E, Henn W, Gruber-Sedlmayr U, Seifert W, Horn D: Novel mutations of the PRKAR1A gene in patients with acrodysostosis. Clin Genet. 2013 Dec;84(6):531-8. doi: 10.1111/cge.12106. Epub 2013 Feb 21. [PubMed:23425300]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01790Sp-Adenosine-3',5'-Cyclic-MonophosphorothioateexperimentalunknownDetails
DB02315Cyclic GMPexperimentalunknownDetails
DB02527Cyclic adenosine monophosphateexperimentalunknownDetails
DB05798GEM-231investigationalunknownDetails