PRKAR2B protein kinase cAMP-dependent type II regulatory subunit beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKAR2Bprovided by HGNC
Official Full Name: protein kinase cAMP-dependent type II regulatory subunit betaprovided by HGNC
Primary source: HGNC:HGNC:9392
See related: Ensembl:ENSG00000005249 MIM:176912; AllianceGenome:HGNC:9392
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PRKAR2; RII-BETA
Summary: 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. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol. [provided by RefSeq, Jul 2008]
Expression: Biased expression in fat (RPKM 215.5), adrenal (RPKM 38.6) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q22.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (107044705..107161811)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (108360790..108477853)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (106685150..106802256)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hypoxia and the hypoxia inducible factor 1alpha activate protein kinase A by repressing RII beta subunit transcription.
Title: Hypoxia and the hypoxia inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription.
PRKAR2B-HIF-1alpha loop promotes aerobic glycolysis and tumour growth in prostate cancer.
Title: PRKAR2B-HIF-1α loop promotes aerobic glycolysis and tumour growth in prostate cancer.
Transcriptional regulation of PRKAR2B by miR-200b-3p/200c-3p and XBP1 in human prostate cancer.
Title: Transcriptional regulation of PRKAR2B by miR-200b-3p/200c-3p and XBP1 in human prostate cancer.
Biochemical studies demonstrate how the removal of ATP primes the holoenzyme for cAMP-mediated activation. The opposing competition between ATP/cAMP is unique to RIalpha..Comparisons to the RIIb holoenzyme demonstrate isoform-specific holoenzyme interfaces and highlights distinct allosteric mechanisms for activation in addition to the structural diversity of the isoforms
Title: Two PKA RIα holoenzyme states define ATP as an isoform-specific orthosteric inhibitor that competes with the allosteric activator, cAMP.
PRKAR2B induces epithelial-mesenchymal transition and promotes castration-resistant prostate cancers metastasis by activating the Wnt/beta-catenin signaling. PRKAR2B might be served as a potential target for castration-resistant prostate cancers therapy.
Title: PRKAR2B promotes prostate cancer metastasis by activating Wnt/β-catenin and inducing epithelial-mesenchymal transition.
In this study, the authors linked for the first time the loss of RIIbeta protein levels to the PRKACA mutation status and found the down-regulation of RIIbeta to arise post-transcriptionally.
Title: Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas.
Study identified the overexpression of PRKAR2B in castration-resistant prostate cancer (CRPC) mouse models and patients, and showed it promoted CRPC cell proliferation, invasion and survival by mainly modulates cell cycle gene expression. These results provide evidence that PRKAR2B is a novel oncogenic gene in CRPC.
Title: PRKAR2B plays an oncogenic role in the castration-resistant prostate cancer.
Release of pRIIbeta in the presence of cAMP is reduced by calcium, whereas autophosphorylation at the phosphorylation site inhibits holoenzyme reassociation with the catalytic subunit.
Title: Single Turnover Autophosphorylation Cycle of the PKA RIIβ Holoenzyme.
Leu206Arg and Leu199_Cys200insTrp mutations in PRKACA impair its association with PRKAR2B and PRKAR1A.
Title: PKA catalytic subunit mutations in adrenocortical Cushing's adenoma impair association with the regulatory subunit.
Although the depletion of PRKAR1A and PRKAR2B in adrenocortical cells has similar effects on cell proliferation and apoptosis; loss of these PKA subunits differentially affects cyclin expression.
Title: Comparison of the effects of PRKAR1A and PRKAR2B depletion on signaling pathways, cell growth, and cell cycle control of adrenocortical cells.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide interaction study of smoking and bladder cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Serine residues Ser6 and Ser9 of HIV-1 Nef are phosphorylated by PKA in a cell-free system; intracellularly, only Ser9 of HIV-1 NL4-3 Nef is phosphorylated by PKA in resting peripheral blood mononuclear cells	PubMed
Tat	tat	HIV-1 Tat induces IL-6 and TNF-alpha expression through the activation of cAMP-dependent protein kinase pathways	PubMed
Vif	vif	Protein kinase A (PKA) binds and phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation	PubMed
Vpr	vpr	HIV-1 Vpr directly interacts with PKA and is phosphorylated at position Ser79 by PKA. PKA activity is necessary for virion-delivered Vpr cell cycle arrest	PubMed
matrix	gag	HIV-1 MA increases phosphorylation and the DNA-binding activity of CREB and c-Myc through activation of the cAMP/PKA and MEK/ERK signaling pathways. Both signaling pathways are synergistically activated upon co-stimulation through the CD19 receptor	PubMed
	gag	Protein kinase A (PKA) has been shown to phosphorylate HIV-1 Matrix in vitro	PubMed
	gag	HIV-1 Matrix impairs proliferation of normal lymphocytes in vitro by inducing the activity of the inhibitory protein kinase A (PKA)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:4585637 (e-PCR)
- UniSTS:44052

SHGC-30240 (e-PCR)
- UniSTS:570

D7S3073 (e-PCR)
- UniSTS:70468

D7S2783 (e-PCR)
- UniSTS:68169

RH69117 (e-PCR)
- UniSTS:63319

SHGC-33294 (e-PCR)
- UniSTS:354

PRKAR2A (e-PCR)
- UniSTS:43893

G36364 (e-PCR)
- UniSTS:56723

G36365 (e-PCR)
- UniSTS:30416

G36363 (e-PCR)
- UniSTS:16861

D7S2773 (e-PCR)
- UniSTS:35317

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cAMP binding	IBA Inferred from Biological aspect of Ancestor more info
enables cAMP-dependent protein kinase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables cAMP-dependent protein kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables cAMP-dependent protein kinase regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IEA Inferred from Electronic Annotation more info
enables protein kinase A catalytic subunit binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase A catalytic subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in learning	IEA Inferred from Electronic Annotation more info
involved_in modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cAMP/PKA signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in response to antipsychotic drug	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of cAMP-dependent protein kinase complex	IBA Inferred from Biological aspect of Ancestor more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary base	TAS Traceable Author Statement more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic shaft	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cAMP-dependent protein kinase type II-beta regulatory subunit

Names: H_RG363E19.2; WUGSC:H_RG363E19.2; cAMP-dependent protein kinase type II-beta regulatory chain; protein kinase, cAMP-dependent, regulatory subunit type II beta; protein kinase, cAMP-dependent, regulatory, type II, beta

NP_002727.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002736.3 → NP_002727.2 cAMP-dependent protein kinase type II-beta regulatory subunit

See identical proteins and their annotated locations for NP_002727.2

Status: REVIEWED

Source sequence(s)

AC006387, AK128639, AL559918, BQ022817, CA405423, CF593944, M31158

Consensus CDS

CCDS5740.1

UniProtKB/Swiss-Prot

A4D0R9, P31323

UniProtKB/TrEMBL

Q6DHZ2

Related

ENSP00000265717.4, ENST00000265717.5

Conserved Domains (3) summary

cd12104
Location:3 → 43

DD_RIIbeta_PKA; Dimerization/Docking domain of the Type II beta Regulatory subunit of cAMP-dependent protein kinase

COG0664
Location:270 → 385

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:154 → 267

CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...