PRKAR2A protein kinase cAMP-dependent type II regulatory subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKAR2Aprovided by HGNC
Official Full Name: protein kinase cAMP-dependent type II regulatory subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:9391
See related: Ensembl:ENSG00000114302 MIM:176910; AllianceGenome:HGNC:9391
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: PKR2; PRKAR2
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. It may interact with various A-kinase anchoring proteins and determine the subcellular localization of cAMP-dependent protein kinase. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER). [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 11.3), colon (RPKM 10.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (48744591..48847874, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (48773615..48876846, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (48784019..48885307, complement)

Chromosome 3 - NC_000003.12 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?

Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss.
Title: Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss.
Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation.
Title: Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation.
Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors.
Title: Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors.
High PK-R2 expression is associated with colorectal cancer.
Title: Expression of prokineticin-receptor2(PK-R2) is a new prognostic factor in human colorectal cancer.
Prkar2a deficiency predisposes to hematopoietic malignancies in vivo. RIIalpha's likely association with HS and DLBCL was hitherto unrecognized and may lead to better understanding of these rare neoplasms.
Title: Hematopoietic neoplasms in Prkar2a-deficient mice.
Disruption of Snapin-PKR2 interaction did not affect PKR2 signaling, but increased the ligand-induced degradation, implying a role of Snapin in the trafficking of PKR2.
Title: Snapin interacts with G-protein coupled receptor PKR2.
we demonstrate that neurochondrin has strong isoform selectivity towards the RIIa subunit of PKA with nanomolar affinity
Title: Neurochondrin is an atypical RIIα-specific A-kinase anchoring protein.
Results show that mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis.
Title: PKA regulatory subunit expression in tooth development.
These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations.
Title: Functional rescue of Kallmann syndrome-associated prokineticin receptor 2 (PKR2) mutants deficient in trafficking.
while there is no change in type II regulatory (RIIalpha) or catalytic (Calpha) subunit expression, site specific RIIalpha (Ser96) and Calpha (Thr197) phosphorylation are increased in heart failure, as well as expression of type I regulatory subunit (RI)
Title: Human heart failure is accompanied by altered protein kinase A subunit expression and post-translational state.

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

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
Envelope surface glycoprotein gp120	env	The exposure of CD4+ T cells to HIV gp120 results in a long-lasting hyporesponsiveness to antigen stimulation through protein kinase A-mediated signaling	PubMed
	env	Treatment of normal human fibroblasts with HIV-1 gp120 protein results in a significant decrease in the levels of 8-azido-[32P]cAMP binding to RI and RII domains of protein kinase A (PKA) and in PKA activity	PubMed
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

D3S3141 (e-PCR)
- UniSTS:12805

D3S3334 (e-PCR)
- UniSTS:24005

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 cAMP-dependent protein kinase regulator activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
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 intracellular signal transduction	TAS Traceable Author Statement more info	PubMed
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

Component	Evidence Code	Pubs
colocalizes_with axoneme	IDA Inferred from Direct Assay more info	PubMed
part_of cAMP-dependent protein kinase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of cAMP-dependent protein kinase complex	IDA Inferred from Direct Assay more info	PubMed
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 extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
part_of nucleotide-activated protein kinase complex	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane raft	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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

Names: cAMP-dependent protein kinase regulatory subunit RII alpha; protein kinase A, RII-alpha subunit; protein kinase, cAMP-dependent, regulatory subunit type II alpha

NP_001308911.1

EC 2.7.11.1

NP_001308912.1

EC 2.7.11.1

NP_001308918.1

EC 2.7.11.1

NP_004148.1

EC 2.7.11.1

XP_005265372.1

EC 2.7.11.1

XP_011532244.1

EC 2.7.11.1

XP_011532245.1

EC 2.7.11.1

XP_047304499.1

EC 2.7.11.1

XP_054203191.1

EC 2.7.11.1

XP_054203192.1

EC 2.7.11.1

XP_054203193.1

EC 2.7.11.1

XP_054203194.1

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_001321982.2 → NP_001308911.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform a

Status: REVIEWED

Source sequence(s)

AA774111, AC141002, AC144546, AK026351, AK293042, DB040049

Consensus CDS

CCDS2778.1

UniProtKB/Swiss-Prot

P13861, Q16823, Q9BUB1

UniProtKB/TrEMBL

A0A024R2W3, A0A0S2Z4E9, A8KAH7

Related

ENSP00000394041.1, ENST00000454963.5

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:255 → 371

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

cd00038
Location:261 → 382

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 ...
NM_001321983.2 → NP_001308912.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform b

Status: REVIEWED

Source sequence(s)

AA774111, AC141002, AC144546, BC002763, DB040049

Consensus CDS

CCDS82771.1

UniProtKB/TrEMBL

A0A0S2Z472, A8KAH7

Related

ENSP00000296446.8, ENST00000296446.12

Conserved Domains (2) summary

cd12103
Location:4 → 44

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

cd00038
Location:139 → 251

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 ...
NM_001321989.2 → NP_001308918.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform c

Status: REVIEWED

Source sequence(s)

AC141002, AC144546

UniProtKB/TrEMBL

A0A9L9PY56, A8KAH7

Related

ENSP00000516455.1, ENST00000706570.1

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:227 → 343

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

cd00038
Location:233 → 354

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 ...
NM_004157.4 → NP_004148.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform a

See identical proteins and their annotated locations for NP_004148.1

Status: REVIEWED

Source sequence(s)

AA774111, AC141002, AC144546, BC002763, CF994284, DB040049, X14968

Consensus CDS

CCDS2778.1

UniProtKB/Swiss-Prot

P13861, Q16823, Q9BUB1

UniProtKB/TrEMBL

A0A024R2W3, A0A0S2Z4E9, A8KAH7

Related

ENSP00000265563.8, ENST00000265563.13

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:255 → 371

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

cd00038
Location:261 → 382

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 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

48744591..48847874 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011533942.4 → XP_011532244.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X1

See identical proteins and their annotated locations for XP_011532244.1

UniProtKB/Swiss-Prot

P13861, Q16823, Q9BUB1

UniProtKB/TrEMBL

A0A024R2W3, A0A0S2Z4E9, A8KAH7

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:255 → 371

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

cd00038
Location:261 → 382

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 ...
XM_047448543.1 → XP_047304499.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X2

UniProtKB/TrEMBL

A0A0S2Z472
XM_005265315.5 → XP_005265372.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X4

UniProtKB/TrEMBL

A0A9L9PXB4

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:135 → 244

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

cd00038
Location:139 → 251

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 ...
XM_011533943.3 → XP_011532245.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X3

UniProtKB/TrEMBL

A0A9L9PXB4

Conserved Domains (3) summary

cd12103
Location:4 → 44

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

COG0664
Location:135 → 244

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

cd00038
Location:139 → 251

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 ...

RNA

XR_002959546.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

48773615..48876846 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054347216.1 → XP_054203191.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X1

UniProtKB/Swiss-Prot

P13861, Q16823, Q9BUB1

UniProtKB/TrEMBL

A0A024R2W3, A0A0S2Z4E9
XM_054347217.1 → XP_054203192.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X2

UniProtKB/TrEMBL

A0A0S2Z472
XM_054347219.1 → XP_054203194.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X4
XM_054347218.1 → XP_054203193.1 cAMP-dependent protein kinase type II-alpha regulatory subunit isoform X3