PKA / TRP channels

Name: cAMP-dependent protein kinase catalytic subunit alpha (PKA)
Official Symbol: PRKACA provided by HGNC
Function:
Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt) Nucleic Acids Res. 40: D71-D75 (2012).
Species External DB Questionmark
Entrez Gene UniprotKB DIP IntAct MINT BioGRID STRING IUPHAR-DB KEGG OMIM
Human
Seq
5566External P17612External DIP-33878NExternal
DIP-46349NExternal
P17612External MINT-95365External 111553External P17612External   hsa:5566External 601639External
Mouse
Seq
18747External P05132External DIP-6086NExternal P05132External MINT-4051347External 202192External P05132External   mmu:18747External  
Rat
Seq
25636External A1L1M0External       247665External A1L1M0External   rno:25636External  
Biological Process:
Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
Disease: No information in OMIM
Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/
Screening Toggle
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC3 Link PKA Inference Prediction 21799177
TRPC6 Link PKA Inference Prediction 21799177
TRPML1 Link PKA Inference Prediction 17988215
TRPV1 Link PKA Inference Prediction 12194871
TRPV2 Link PKA Inference Prediction 15249591
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC3 Link PKA Co-immunoprecipitation HEK293 Not specified Full-length Not used 21799177
TRPC6 Link PKA Co-immunoprecipitation HEK293 Mouse Full-length Not used 21799177
TRPC6 Link PKA Co-immunoprecipitation HEK293T Human Full-length Not specified Not specified 23645677
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPC6 Link PKA In vitro PTM assay Phosphorylation (Thr-69) 22001259
TRPC6 Link PKA In vitro PTM assay Phosphorylation (Ser-28) 22001259
TRPC6 Link PKA In vitro PTM assay Phosphorylation (Thr-70) 23645677
TRPC6 Link PKA In vivo PTM assay Phosphorylation (Thr-70) 23645677
TRPML1 Link PKA In vitro PTM assay Phosphorylation (Ser-557) 17988215
TRPML1 Link PKA In vivo PTM assay Phosphorylation (Ser-559) 17988215
TRPML1 Link PKA Patch clamp Inhibition 17988215
TRPP1 Link PKA In vitro PTM assay Phosphorylation (Ser-829) 23390129
TRPV1 Link PKA In vitro PTM assay Phosphorylation (Ser-116) 12194871
TRPV1 Link PKA Patch clamp Activation 12194871
TRPV2 Link PKA In vitro PTM assay Phosphorylation 15249591
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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