cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B)
The protein contains 418 amino acids for an estimated molecular weight of 46302 Da.
Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs3729881 |
Biological Process
Activation of phospholipase C activity
Activation of protein kinase A activity
Blood coagulation
Cellular response to glucagon stimulus
CGMP-mediated signaling
Chemical synaptic transmission
Ciliary basal body-plasma membrane docking
Energy reserve metabolic process
Epidermal growth factor receptor signaling pathway
Fatty acid metabolic process
Fibroblast growth factor receptor signaling pathway
G2/M transition of mitotic cell cycle
Innate immune response
Intracellular signal transduction
Learning
Mitotic cell cycle
Modulation of chemical synaptic transmission
Negative regulation of cAMP-dependent protein kinase activity
Negative regulation of inflammatory response to antigenic stimulus
Neurotrophin TRK receptor signaling pathway
Organelle organization
Regulation of cAMP-mediated signaling
Regulation of G2/M transition of mitotic cell cycle
Regulation of insulin secretion
Regulation of protein kinase A signaling
Renal water homeostasis
Response to antipsychotic drug
Response to clozapine
Signal transduction
Small molecule metabolic process
Transmembrane transport
Water transport
The reference OMIM entry for this protein is 176912
Protein kinase, camp-dependent, regulatory, type ii, beta; prkar2b
Prkar2
Rii-beta
DESCRIPTION
The cAMP-dependent protein kinase system is believed to mediate most, if not all, cellular effects of the second messenger cAMP. The kinase holoenzyme consists of 2 regulatory (R) and 2 catalytic (C) subunits that dissociate upon the binding of 2 cAMP molecules to each of the R subunits. The free, activated C subunits then catalyze the phosphorylation of specific substrate proteins on serine and threonine residues and thereby alter their activity or function. PRKAR2B is 1 of several R subunits (Levy et al., 1988).CLONING
Using rat Prkar2b as probe, Levy et al. (1988) cloned PRKAR2B, which they designated RII-beta, from a human testis cDNA library. The deduced 418-amino acid protein has a calculated molecular mass of about 54 kD. PRKAR2B contains an N-terminal dimerization domain, an autophosphorylation site (ser114), and 7 potential polyadenylation signals. The human and rat proteins share 97% homology. Northern blot analysis revealed a 3.3-kb transcript expressed at highest levels in testis, fallopian tubes, and ovary. Low or undetectable levels were found in myocardium, parotid gland, parotid tumor, epididymis, uterus, placenta, and umbilical cord. Northern blot analysis also detected cAMP-stimulated Prkar2b expression in rat Sertoli cell cultures.GENE STRUCTURE
Levy et al. (1988) estimated the size of the PRKAR2B gene to be close to 28 kb.MAPPING
Using both a rat skeletal muscle clone and a human clone of type II regulatory subunit of cyclic AMP-dependent protein kinase, Scambler et al. (1987) demonstrated that the human gene is located on chromosome 7, close to but separate from the cystic fibrosis locus (219700). These conclusions were based on Southern blot analysis of DNA from hybrid cell lines containing only chromosome 7 or parts thereof, as well as human/mouse hybrid cell lines established by means of chromosome-mediated gene transfer (CMGT) using MET (164860) as a dominant selectable marker. Independence of PKR2 from CF was also indicated by family linkage studies using a RFLP of the PKR2 probe. Wainwright et al. (1987) showed that PKR2 is linked to several markers on 7q. The closest and strongest linkage was to TCRB (see 186930), which showed a maximum lod score of 3.01 at theta = 0.00. Using RFLPs in the CEPH panel of 40 families, Solberg et al. (1992) mapped the regulatory subunit RII-beta of cAMP-dependent protein kinase to 7q. They constructed a 7-point framework map including PRKAR2B and demonstrated the following order: cen--D7S371--(COL1A2, D7S79)--PRKAR2B--MET--D7S87--TCRB--qter. Furthermore, by in situ hybridization to metaphase chromosomes, Solberg et al. (1992) physically mapped PRKAR2B to 7q22.BIOCHEMICAL FEATURES
- Crystal Structure Zhang et al. (2012) described the 2.3-angstrom structure of full-length tetrameric RII-beta(2):catalytic subunit-alpha(2) (see 601639) holoenzyme. The structure showing a dimer of dimers provided a mechanistic understanding of allosteric activation by cAMP. The heterodimers are anchored together by an interface created by the beta-4/beta-5 loop in the RII-beta subunit, which docks onto the carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C subunit into a fully closed conformation in the absence of nucleotide. Diffusion of magnesium ATP into these crystals trapped not ATP but the reaction products adenosine diphosphate and the phosphorylated RII-beta subunit. This complex has implications for t ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176912 was added.