# TRIP Database

Mammalian TRansient receptor potential channel-Interacting Protein

TRP channels

- TRPC
  - TRPC1
  - TRPC2
  - TRPC3
  - TRPC4
  - TRPC5
  - TRPC6
  - TRPC7
- TRPV
  - TRPV1
  - TRPV2
  - TRPV3
  - TRPV4
  - TRPV5
  - TRPV6
- TRPM
  - TRPM1
  - TRPM2
  - TRPM3
  - TRPM4
  - TRPM5
  - TRPM6
  - TRPM7
  - TRPM8
- TRPML
  - TRPML1
  - TRPML2
  - TRPML3
- TRPP
  - TRPP1
  - TRPP2
  - TRPP3
- TRPA
  - TRPA1

» Citation

# PKA / TRP channels

- Basic Information
- External Database
- PPI pairs (6)
- Biological Process (30)
- Disease (0)

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
Name | Description
--- | ---
Entrez Gene | A database that contains genome-centered information
UniprotKB | The central hub for collection of functional information on proteins
DIP | A database that documents experimentally determined PPIs
IntAct | An open source database and software suite for modeling, storing and analyzing molecular interaction data
MINT | A database that collects experimentally verified PPIs in a binary or complex representation
BioGRID | A database of known and predicted PPIs
STRING | An online interaction repository with data
IUPHAR-DB | Integrated pharmacological and pathophysiological information on GPCR and voltage-gated & ligand-gated ion channels
KEGG | A database resource consisting of 16 main databases, categorized into systems information, genomic information, and chemical information
OMIM | A database of human genes and genetic disorders
Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM
Human | 5566 | P17612 | DIP-33878N DIP-46349N | P17612 | MINT-95365 | 111553 | P17612 |  | hsa:5566 | 601639
Mouse | 18747 | P05132 | DIP-6086N | P05132 | MINT-4051347 | 202192 | P05132 |  | mmu:18747 |
Rat | 25636 | A1L1M0 |  |  |  | 247665 | A1L1M0 |  | rno:25636 |

PPI pairs:

TRPC3 | TRPC6 | TRPML1 | TRPP1 | TRPV1 | TRPV2

Biological Process:

- GO:0007202 : activation of phospholipase C activity
- GO:0034199 : activation of protein kinase A activity
- GO:0007596 : blood coagulation
- GO:0071377 : cellular response to glucagon stimulus
- GO:0071333 : cellular response to glucose stimulus
- GO:0071374 : cellular response to parathyroid hormone stimulus
- GO:0006112 : energy reserve metabolic process
- GO:0007173 : epidermal growth factor receptor signaling pathway
- GO:0008543 : fibroblast growth factor receptor signaling pathway
- GO:0000086 : G2/M transition of mitotic cell cycle
- GO:0006094 : gluconeogenesis
- GO:0007243 : intracellular protein kinase cascade
- GO:0001707 : mesoderm formation
- GO:0051447 : negative regulation of meiotic cell cycle
- GO:0048011 : nerve growth factor receptor signaling pathway
- GO:0018105 : peptidyl-serine phosphorylation
- GO:0071158 : positive regulation of cell cycle arrest
- GO:0046827 : positive regulation of protein export from nucleus
- GO:0046777 : protein autophosphorylation
- GO:0043457 : regulation of cellular respiration
- GO:0050796 : regulation of insulin secretion
- GO:0045667 : regulation of osteoblast differentiation
- GO:0061136 : regulation of proteasomal protein catabolic process
- GO:0051966 : regulation of synaptic transmission, glutamatergic
- GO:2000810 : regulation of tight junction assembly
- GO:0044281 : small molecule metabolic process
- GO:0048240 : sperm capacitation
- GO:0055085 : transmembrane transport
- GO:0019433 : triglyceride catabolic process
- GO:0006833 : water transport

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 Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Screening
| Experimental screening | Non-experimental screening | Reference
--- | --- | --- | ---
TRP channel construct | Interactor source
TRP channel |  | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type
TRPC3 |  | PKA | Inference |  |  |  |  |  | Prediction | 21799177
TRPC6 |  | PKA | Inference |  |  |  |  |  | Prediction | 21799177
TRPML1 |  | PKA | Inference |  |  |  |  |  | Prediction | 17988215
TRPV1 |  | PKA | Inference |  |  |  |  |  | Prediction | 12194871
TRPV2 |  | PKA | Inference |  |  |  |  |  | Prediction | 15249591

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Validation: In vivo validation
| 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 |  | PKA | Co-immunoprecipitation |  | HEK293 | Not specified | Full-length | Not used |  | 21799177
TRPC6 |  | PKA | Co-immunoprecipitation |  | HEK293 | Mouse | Full-length | Not used |  | 21799177
TRPC6 |  | PKA | Co-immunoprecipitation |  | HEK293T | Human | Full-length | Not specified | Not specified | 23645677

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

Screening Validation: In vitro validation Validation: In vivo validation Characterization Functional consequence | top

Functional consequence
TRP channel |  | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference
--- | --- | --- | --- | --- | --- | --- | ---
TRPC6 |  | PKA | In vitro PTM assay | Phosphorylation (Thr-69) |  |  | 22001259
TRPC6 |  | PKA | In vitro PTM assay | Phosphorylation (Ser-28) |  |  | 22001259
TRPC6 |  | PKA | In vitro PTM assay | Phosphorylation (Thr-70) |  |  | 23645677
TRPC6 |  | PKA | In vivo PTM assay | Phosphorylation (Thr-70) |  |  | 23645677
TRPML1 |  | PKA | In vitro PTM assay | Phosphorylation (Ser-557) |  |  | 17988215
TRPML1 |  | PKA | In vivo PTM assay | Phosphorylation (Ser-559) |  |  | 17988215
TRPML1 |  | PKA | Patch clamp |  |  | Inhibition | 17988215
TRPP1 |  | PKA | In vitro PTM assay | Phosphorylation (Ser-829) |  |  | 23390129
TRPV1 |  | PKA | In vitro PTM assay | Phosphorylation (Ser-116) |  |  | 12194871
TRPV1 |  | PKA | Patch clamp |  |  | Activation | 12194871
TRPV2 |  | PKA | In vitro PTM assay | Phosphorylation |  |  | 15249591

(: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Name Email Title* Comment* TRP
/ Interactor
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