Scientific Background: PRKAR1A or the cAMP-dependent protein kinase regulatory subunit type I alpha, is part of the type 1 PKA holoenzyme. PRKAR1A is found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids (1). Mutations in PRKAR1A gene cause Carney complex (CNC) and PRKAR1A can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2 (2). A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40).
2. Casey M, et al: Mutations in the protein kinase A R1-alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J. Clin. Invest. 106: R31-R38, 2000.
NCBI and Uniprot Product Information
NCBI Description
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme 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 have been identified in humans. This gene encodes 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. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]
Uniprot Description
Function: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Ref.10 Ref.20
Subunit structure: The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3
By similarity. Interacts with PRKX; regulates this cAMP-dependent protein kinase. Interacts with C2orf88/smAKAP; this interaction may target PRKAR1A to the plasma membrane. Interacts with AICDA. Ref.8 Ref.10 Ref.11 Ref.20 Ref.24 Ref.27
Subcellular location: Cell membrane Ref.27.
Tissue specificity: Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.
Post-translational modification: The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.
Involvement in disease: Carney complex 1 (CNC1) [MIM:160980]: CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.28 Ref.29 Ref.30Intracardiac myxoma (INTMYX) [MIM:255960]: Inheritance is autosomal recessive.Note: The disease is caused by mutations affecting the gene represented in this entry.Primary pigmented nodular adrenocortical disease 1 (PPNAD1) [MIM:610489]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7Acrodysostosis 1, with or without hormone resistance (ACRDYS1) [MIM:101800]: A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35
Sequence similarities: Belongs to the cAMP-dependent kinase regulatory chain family.Contains 2 cyclic nucleotide-binding domains.
Research Articles on PRKAR1A
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Product Notes
The PRKAR1A prkar1a (Catalog #AAA515098) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is His tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant full-length human PRKAR1A Protein was expressed in Sf9 insect cells. AAA Biotech's PRKAR1A can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the PRKAR1A prkar1a for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "PRKAR1A, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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