Page last updated: 2024-10-24

thrombin-activated receptor activity

Definition

Target type: molecularfunction

A G protein-coupled receptor activity that is activated by cleavage by thrombin, which exposes a tethered ligand corresponding to the new N-terminus, which binds to the receptor and activates it. [GOC:ai, GOC:pg, PMID:20423334]

Thrombin-activated receptor (PAR) activity involves a complex cascade of molecular events that ultimately lead to cellular signaling and various physiological responses. PARs are G protein-coupled receptors (GPCRs) that are activated by proteolytic cleavage of their N-terminal extracellular domain. Thrombin, a serine protease, is a key activator of PARs, particularly PAR1 and PAR4.

Upon thrombin cleavage, the newly exposed N-terminus of the PAR acts as a tethered ligand, binding to the receptor's extracellular domain and initiating signaling. This interaction triggers a conformational change in the receptor, leading to the activation of intracellular signaling pathways.

The activation of PARs by thrombin can initiate a variety of downstream events, including:

- **G protein activation:** PARs couple to heterotrimeric G proteins, primarily Gq and Gi. The activation of Gq leads to the activation of phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 promotes calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
- **MAP kinase signaling:** PAR activation can activate the mitogen-activated protein kinase (MAPK) signaling pathway, leading to the phosphorylation of various downstream targets involved in cell proliferation, differentiation, and survival.
- **Calcium signaling:** The release of calcium from intracellular stores, triggered by IP3, plays a critical role in a wide range of cellular processes, including muscle contraction, secretion, and gene expression.
- **Cytoskeletal rearrangement:** PAR activation can induce changes in the cytoskeleton, leading to cell migration, adhesion, and wound healing.
- **Transcriptional regulation:** PARs can regulate gene expression by influencing the activity of transcription factors, affecting the synthesis of proteins involved in various cellular functions.

In summary, thrombin-activated receptor activity is a multifaceted process that involves the proteolytic cleavage of PARs, leading to the activation of G proteins, calcium signaling, MAP kinase signaling, and cytoskeletal rearrangement. These events ultimately result in a diverse range of physiological responses, including platelet aggregation, smooth muscle contraction, inflammation, and tissue repair.'
"

Proteins (3)

ProteinDefinitionTaxonomy
Proteinase-activated receptor 4A proteinase-activated receptor 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q96RI0]Homo sapiens (human)
Proteinase-activated receptor 2A proteinase-activated receptor 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55085]Homo sapiens (human)
Proteinase-activated receptor 1A proteinase-activated receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P25116]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first sourcechromones;
morpholines;
organochlorine compound
autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
ultram2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol : A tertiary alcohol that is cyclohexanol substituted at positions 1 and 2 by 3-methoxyphenyl and dimethylaminomethyl groups respectively.aromatic ether;
tertiary alcohol;
tertiary amino compound
triptolidediterpenoid;
epoxide;
gamma-lactam;
organic heteroheptacyclic compound
antispermatogenic agent;
plant metabolite
omega-n-methylarginineN(omega)-methyl-L-arginine : A L-arginine derivative with a N(omega)-methyl substituent.

omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.
amino acid zwitterion;
arginine derivative;
guanidines;
L-arginine derivative;
non-proteinogenic L-alpha-amino acid
vu0099704VU0099704: an antagonist of protease activated receptor 4 (PAR-4); structure in first source
2-bromo-N-[3-(1-oxopropylamino)phenyl]benzamidebenzamides
2-bromo-N-[3-(1-oxobutylamino)phenyl]benzamidebenzamides
sch 79797quinazolines
morphineMeconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound
anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamideseryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide: a proteinase-activated receptor-2-activating peptide; SL-NH2 is NOT Ser-Leu-NH2 here
tapentadolTapentadol: An opioid analgesic, MU OPIOID RECEPTOR agonist, and noradrenaline reuptake inhibitor that is used in the treatment of moderate to severe pain, and of pain associated with DIABETIC NEUROPATHIES.alkylbenzene
o-demethyltramadolalkylbenzene;
ring assembly
rwj-56110RWJ-56110: a PAR-1 antagonist; structure in first source
vorapaxarvorapaxar : A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation.

vorapaxar: has antiplatelet activity; structure in first source
carbamate ester;
lactone;
naphthofuran;
organofluorine compound;
pyridines
cardiovascular drug;
platelet aggregation inhibitor;
protease-activated receptor-1 antagonist
2-furoyl-ligrlo-amide2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2 agonist
e 5555E 5555: a 2-iminopyridine derivative and platelet aggregation inhibitoraromatic ketone
zstk474ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase.benzimidazoles;
morpholines;
organofluorine compound;
triamino-1,3,5-triazine
antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
AZ3451benzimidazoles;
benzodioxoles;
nitrile;
organobromine compound;
secondary carboxamide
anti-inflammatory agent;
autophagy inducer;
PAR2 negative allosteric modulator