Urotensin-2 receptor

Function

G protein-coupled receptor for the vasoactive neuropeptides urotensin-2 and urotensin-2B. Upon ligand binding, activates intracellular signaling cascades via G protein coupling, primarily through Gq/11, leading to phospholipase C activation, increased intracellular calcium, and activation of protein kinase C (PKC). Through coupling to G(i)/G(o) alpha subunits, stimulates MAPK/ERK pathways and thereby contributes to regulation of vascular tone, cardiac contractility, and cell proliferation. Ligand binding also triggers a marked reduction in the biogenesis of autophagosomes by inhibiting the recruitment of ATG16L1 to pre-autophagosomal endocytic vesicles.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Urot_II_rcpt

Functional cluster

Nucleic Acid Metabolism & Repair Enzymes

Experimental structures · PDB · 2

• 6HVK NMR
• 9JFK EM 3.23A

A predicted model is available from AlphaFold.

Gene Ontology · 9

• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0004930 G protein-coupled receptor activity
• GO:0001604 urotensin II receptor activity
• GO:0008015 blood circulation
• GO:0097746 blood vessel diameter maintenance
• GO:0007218 neuropeptide signaling pathway
• GO:0008217 regulation of blood pressure
• GO:0007165 signal transduction

Drugs targeting this protein · 1

• PALOSURAN antagonist

Related proteins · sequence + function similarity

• Urotensin-2 receptor 1.00
• Urotensin-2 receptor 0.93
• Leukotriene B4 receptor 2 0.91
• B1 bradykinin receptor 0.90
• C-X-C chemokine receptor GPR25 0.90
• Leukotriene B4 receptor 2 0.90
• Leukotriene B4 receptor 2 0.90
• Motilin receptor 0.90
• C-X-C chemokine receptor GPR25 0.90
• Neuropeptides B/W receptor type 1 0.89
• Urotensin-2 receptor 0.89
• Galanin receptor type 3 0.89

Co-cited proteins · studied together in the literature

• Urotensin-2 1 shared papers
• Urotensin-2B 1 shared papers
• Urotensin-2B 1 shared papers
• Urotensin-2B 1 shared papers
• Urotensin-2 receptor 1 shared papers

Literature · 8 cited papers

• Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis. Autophagy · 2016
• State-dependent calcium mobilization by urotensin-II in cultured human endothelial cells. Peptides · 2008
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The expression of urotensin II receptor (U2R) is up-regulated by interferon-gamma. J. Recept. Signal Transduct. · 2003
• Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain. Biochem. Biophys. Res. Commun. · 2003
• Urotensin II mediates ERK1/2 phosphorylation and proliferation in GPR14-transfected cell lines. J. Recept. Signal Transduct. · 2002
• Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature · 1999