PRKAR1A: Difference between revisions

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{{Infobox_gene}}
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'''cAMP-dependent protein kinase type I-alpha regulatory subunit''' is an [[enzyme]] that in humans is encoded by the ''PRKAR1A'' [[gene]].<ref name="pmid3479018">{{cite journal | vauthors = Scambler P, Oyen O, Wainwright B, Farrall M, Law HY, Estivill X, Sandberg M, Williamson R, Jahnsen T | title = Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis | journal = Am J Hum Genet | volume = 41 | issue = 5 | pages = 925–32 | date = December 1987 | pmid = 3479018 | pmc = 1684338 | doi =  }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_PRKAR1A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ne4.
| PDB = {{PDB2|1ne4}}, {{PDB2|1ne6}}, {{PDB2|1rgs}}, {{PDB2|1rl3}}, {{PDB2|1u7e}}, {{PDB2|2ezw}}
| Name = Protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)
| HGNCid = 9388
| Symbol = PRKAR1A
| AltSymbols =; CAR; CNC; CNC1; DKFZp779L0468; MGC17251; PKR1; PRKAR1; TSE1
| OMIM = 188830
| ECnumber = 
| Homologene = 37664
| MGIid = 104878
| GeneAtlas_image1 = PBB_GE_PRKAR1A_200603_at_tn.png
| GeneAtlas_image2 = PBB_GE_PRKAR1A_200604_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_PRKAR1A_200605_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008603 |text = cAMP-dependent protein kinase regulator activity}} {{GNF_GO|id=GO:0016301 |text = kinase activity}} {{GNF_GO|id=GO:0030552 |text = cAMP binding}}
| Component = {{GNF_GO|id=GO:0005952 |text = cAMP-dependent protein kinase complex}} {{GNF_GO|id=GO:0031594 |text = neuromuscular junction}}
  | Process = {{GNF_GO|id=GO:0001707 |text = mesoderm formation}} {{GNF_GO|id=GO:0006357 |text = regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5573
    | Hs_Ensembl = ENSG00000108946
    | Hs_RefseqProtein = NP_002725
    | Hs_RefseqmRNA = NM_002734
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 64019705
    | Hs_GenLoc_end = 64040503
    | Hs_Uniprot = P10644
    | Mm_EntrezGene = 19084
    | Mm_Ensembl = ENSMUSG00000020612
    | Mm_RefseqmRNA = NM_021880
    | Mm_RefseqProtein = NP_068680
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 109466334
    | Mm_GenLoc_end = 109485746
    | Mm_Uniprot = Q3UBA7
  }}
}}
'''Protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)''', also known as '''PRKAR1A''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
| section_title =  
| summary_text = cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase (AMPK), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of AMPK 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 AMPK 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. 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. Three alternatively spliced transcript variants encoding the same protein have been observed.<ref>{{cite web | title = Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573| accessdate = }}</ref>
}}


Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.{{Fact|date=December 2007}}
[[Cyclic adenosine monophosphate|cAMP]] is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase A ([[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.<ref name = "entrez">{{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| accessdate = }}</ref>


==See also==
== 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.<ref name = "entrez"/>
 
Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.{{Citation needed|date=December 2007}}
 
== Interactions ==
 
PRKAR1A has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[AKAP10]],<ref name = pmid9326583>{{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}}</ref><ref name = pmid16189514>{{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 }}</ref>
* [[AKAP1]],<ref name = pmid12634056>{{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}}</ref><ref name = pmid10764601>{{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 }}</ref>
* [[AKAP4]],<ref name = pmid12606363>{{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 }}</ref><ref name = pmid9852104>{{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}}</ref>
* [[ARFGEF1]],<ref name = pmid12571360>{{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 }}</ref>
* [[ARFGEF2]],<ref name = pmid12571360/>
* [[Grb2]],<ref name = pmid9050991>{{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 }}</ref>
* [[MYO7A]],<ref name = pmid10889203>{{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 }}</ref>
* [[PRKAR1B]],<ref name = pmid12634056/><ref name = pmid8407966>{{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 | pmid = 8407966 | doi =  }}</ref>  and
* [[UBE2M]].<ref name = pmid17353931>{{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 | issue =  | pages = 89 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }}</ref>
{{Div col end}}
 
== See also ==
*[[cAMP-dependent protein kinase]]
*[[cAMP-dependent protein kinase]]


==References==
== References ==
{{reflist|2}}
{{reflist|35em}}
==Further reading==
 
{{refbegin | 2}}
== Further reading ==
{{PBB_Further_reading
{{refbegin |35em}}
| citations =
* {{cite journal | vauthors = Stratakis CA | title = 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) | journal = Ann. N. Y. Acad. Sci. | volume = 968 | issue =  | pages = 3–21 | year = 2002 | pmid = 12119264 | doi = 10.1111/j.1749-6632.2002.tb04323.x }}
*{{cite journal | author=Stratakis CA |title=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). |journal=Ann. N. Y. Acad. Sci. |volume=968 |issue=  |pages= 3-21 |year= 2002 |pmid= 12119264 |doi= }}
* {{cite journal | vauthors = Bourdeau I, Stratakis CA | title = Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease | journal = Ann. N. Y. Acad. Sci. | volume = 968 | issue =  | pages = 240–55 | year = 2002 | pmid = 12119280 | doi = 10.1111/j.1749-6632.2002.tb04339.x }}
*{{cite journal | author=Bourdeau I, Stratakis CA |title=Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease. |journal=Ann. N. Y. Acad. Sci. |volume=968 |issue=  |pages= 240-55 |year= 2002 |pmid= 12119280 |doi= }}
* {{cite journal | vauthors = Alto N, Carlisle Michel JJ, Dodge KL, Langeberg LK, Scott JD | title = Intracellular targeting of protein kinases and phosphatases | journal = Diabetes | volume = 51 Suppl 3 | issue =  | pages = S385–8 | year = 2003 | pmid = 12475780 | doi = 10.2337/diabetes.51.2007.s385 }}
*{{cite journal | author=Alto N, Carlisle Michel JJ, Dodge KL, ''et al.'' |title=Intracellular targeting of protein kinases and phosphatases. |journal=Diabetes |volume=51 Suppl 3 |issue=  |pages= S385-8 |year= 2003 |pmid= 12475780 |doi= }}
* {{cite journal | vauthors = Stergiopoulos SG, Stratakis CA | title = Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease! | journal = FEBS Lett. | volume = 546 | issue = 1 | pages = 59–64 | year = 2003 | pmid = 12829237 | doi = 10.1016/S0014-5793(03)00452-6 }}
*{{cite journal | author=Stergiopoulos SG, Stratakis CA |title=Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease! |journal=FEBS Lett. |volume=546 |issue= 1 |pages= 59-64 |year= 2003 |pmid= 12829237 |doi= }}
* {{cite journal | vauthors = Bossis I, Stratakis CA | title = Minireview: PRKAR1A: normal and abnormal functions | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5452–8 | year = 2004 | pmid = 15331577 | doi = 10.1210/en.2004-0900 }}
*{{cite journal | author=Bossis I, Stratakis CA |title=Minireview: PRKAR1A: normal and abnormal functions. |journal=Endocrinology |volume=145 |issue= 12 |pages= 5452-8 |year= 2004 |pmid= 15331577 |doi= 10.1210/en.2004-0900 }}
* {{cite journal | vauthors = Cho-Chung YS, Nesterova MV | title = Tumor reversion: protein kinase A isozyme switching | journal = Ann. N. Y. Acad. Sci. | volume = 1058 | issue =  | pages = 76–86 | year = 2006 | pmid = 16394127 | doi = 10.1196/annals.1359.014 }}
*{{cite journal | author=Cho-Chung YS, Nesterova MV |title=Tumor reversion: protein kinase A isozyme switching. |journal=Ann. N. Y. Acad. Sci. |volume=1058 |issue=  |pages= 76-86 |year= 2006 |pmid= 16394127 |doi= 10.1196/annals.1359.014 }}
* {{cite journal | vauthors = Lytras A, Tolis G | title = Growth hormone-secreting tumors: genetic aspects and data from animal models | journal = Neuroendocrinology | volume = 83 | issue = 3–4 | pages = 166–78 | year = 2006 | pmid = 17047380 | doi = 10.1159/000095525 }}
*{{cite journal | author=Lytras A, Tolis G |title=Growth hormone-secreting tumors: genetic aspects and data from animal models. |journal=Neuroendocrinology |volume=83 |issue= 3-4 |pages= 166-78 |year= 2006 |pmid= 17047380 |doi= 10.1159/000095525 }}
* {{cite journal | vauthors = Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L | title = Will diverse Tat interactions lead to novel antiretroviral drug targets? | journal = Current drug targets | volume = 7 | issue = 12 | pages = 1595–606 | year = 2007 | pmid = 17168834 | doi = 10.2174/138945006779025338 }}
*{{cite journal | author=Harrich D, McMillan N, Munoz L, ''et al.'' |title=Will diverse Tat interactions lead to novel antiretroviral drug targets? |journal=Current drug targets |volume=7 |issue= 12 |pages= 1595-606 |year= 2007 |pmid= 17168834 |doi= }}
* {{cite journal | vauthors = Boshart M, Weih F, Nichols M, Schütz G | title = The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase | journal = Cell | volume = 66 | issue = 5 | pages = 849–59 | year = 1991 | pmid = 1832337 | doi = 10.1016/0092-8674(91)90432-X }}
*{{cite journal | author=Boshart M, Weih F, Nichols M, Schütz G |title=The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase. |journal=Cell |volume=66 |issue= 5 |pages= 849-59 |year= 1991 |pmid= 1832337 |doi= }}
* {{cite journal | vauthors = Jones KW, Shapero MH, Chevrette M, Fournier RE | title = Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A | journal = Cell | volume = 66 | issue = 5 | pages = 861–72 | year = 1991 | pmid = 1889088 | doi = 10.1016/0092-8674(91)90433-Y }}
*{{cite journal | author=Jones KW, Shapero MH, Chevrette M, Fournier RE |title=Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A. |journal=Cell |volume=66 |issue= 5 |pages= 861-72 |year= 1991 |pmid= 1889088 |doi= }}
* {{cite journal | vauthors = Hofmann B, Nishanian P, Baldwin RL, Insixiengmay P, Nel A, Fahey JL | title = HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism | journal = J. Immunol. | volume = 145 | issue = 11 | pages = 3699–705 | year = 1991 | pmid = 1978848 | doi =  }}
*{{cite journal | author=Hofmann B, Nishanian P, Baldwin RL, ''et al.'' |title=HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism. |journal=J. Immunol. |volume=145 |issue= 11 |pages= 3699-705 |year= 1991 |pmid= 1978848 |doi=  }}
* {{cite journal | vauthors = Sandberg M, Skålhegg B, Jahnsen T | title = 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 | journal = Biochem. Biophys. Res. Commun. | volume = 167 | issue = 1 | pages = 323–30 | year = 1990 | pmid = 2310396 | doi = 10.1016/0006-291X(90)91768-N }}
*{{cite journal | author=Sandberg M, Skålhegg B, Jahnsen T |title=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. |journal=Biochem. Biophys. Res. Commun. |volume=167 |issue= 1 |pages= 323-30 |year= 1990 |pmid= 2310396 |doi= }}
* {{cite journal | vauthors = Lem J, Chin AC, Thayer MJ, Leach RJ, Fournier RE | title = Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 19 | pages = 7302–6 | year = 1988 | pmid = 2902627 | pmc = 282174 | doi = 10.1073/pnas.85.19.7302 }}
*{{cite journal | author=Lem J, Chin AC, Thayer MJ, ''et al.'' |title=Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 19 |pages= 7302-6 |year= 1988 |pmid= 2902627 |doi= }}
* {{cite journal | vauthors = Sandberg M, Taskén K, Oyen O, Hansson V, Jahnsen T | title = Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis | journal = Biochem. Biophys. Res. Commun. | volume = 149 | issue = 3 | pages = 939–45 | year = 1988 | pmid = 3426618 | doi = 10.1016/0006-291X(87)90499-2 }}
*{{cite journal | author=Sandberg M, Taskén K, Oyen O, ''et al.'' |title=Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis. |journal=Biochem. Biophys. Res. Commun. |volume=149 |issue= 3 |pages= 939-45 |year= 1988 |pmid= 3426618 |doi= }}
* {{cite journal | vauthors = Geahlen RL, Carmichael DF, Hashimoto E, Krebs EG | title = Phosphorylation of cAMP-dependent protein kinase subunits | journal = Adv. Enzyme Regul. | volume = 20 | issue = | pages = 195–209 | year = 1982 | pmid = 6287816 | doi = 10.1016/0065-2571(82)90016-4 }}
*{{cite journal | author=Scambler P, Oyen O, Wainwright B, ''et al.'' |title=Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis. |journal=Am. J. Hum. Genet. |volume=41 |issue= 5 |pages= 925-32 |year= 1987 |pmid= 3479018 |doi= }}
* {{cite journal | vauthors = Guild BC, Strominger JL | title = 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 | journal = J. Biol. Chem. | volume = 259 | issue = 21 | pages = 13504–10 | year = 1984 | pmid = 6333425 | doi =  }}
*{{cite journal | author=Geahlen RL, Carmichael DF, Hashimoto E, Krebs EG |title=Phosphorylation of cAMP-dependent protein kinase subunits. |journal=Adv. Enzyme Regul. |volume=20 |issue= |pages= 195-209 |year= 1982 |pmid= 6287816 |doi=  }}
* {{cite journal | vauthors = Bongarzone I, Monzini N, Borrello MG, Carcano C, Ferraresi G, Arighi E, Mondellini P, Della Porta G, Pierotti MA | title = 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 | journal = Mol. Cell. Biol. | volume = 13 | issue = 1 | pages = 358–66 | year = 1993 | pmid = 7678053 | pmc = 358915 | doi =  }}
*{{cite journal | author=Guild BC, Strominger JL |title=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. |journal=J. Biol. Chem. |volume=259 |issue= 21 |pages= 13504-10 |year= 1984 |pmid= 6333425 |doi=  }}
* {{cite journal | vauthors = Hofmann B, Nishanian P, Nguyen T, Insixiengmay P, Fahey JL | title = Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 14 | pages = 6676–80 | year = 1993 | pmid = 7688126 | pmc = 46995 | doi = 10.1073/pnas.90.14.6676 }}
*{{cite journal | author=Bongarzone I, Monzini N, Borrello MG, ''et al.'' |title=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. |journal=Mol. Cell. Biol. |volume=13 |issue= 1 |pages= 358-66 |year= 1993 |pmid= 7678053 |doi= }}
* {{cite journal | vauthors = Hofmann B, Nishanian P, Fan J, Nguyen T, Fahey JL | title = HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro | journal = AIDS | volume = 8 | issue = 7 | pages = 1016–7 | year = 1994 | pmid = 7946090 | doi = 10.1097/00002030-199407000-00025 }}
*{{cite journal | author=Hofmann B, Nishanian P, Nguyen T, ''et al.'' |title=Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 14 |pages= 6676-80 |year= 1993 |pmid= 7688126 |doi= }}
*{{cite journal  | author=Hofmann B, Nishanian P, Fan J, ''et al.'' |title=HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro. |journal=AIDS |volume=8 |issue= 7 |pages= 1016-7 |year= 1994 |pmid= 7946090 |doi=  }}
}}
{{refend}}
{{refend}}


{{PDB Gallery|geneid=5573}}
{{Intracellular signaling peptides and proteins}}
{{NLM content}}
{{NLM content}}
{{protein-stub}}


[[Category:Signal transduction]]
[[Category:Signal transduction]]
{{WikiDoc Sources}}

Latest revision as of 00:59, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

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.[2]

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.[2]

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

Interactions

PRKAR1A has been shown to interact with:

See also

References

  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. ↑ 2.0 2.1 "Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)".
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 5.0 5.1 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.

Further reading

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

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