Substance-K receptor

Function

This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). Is also able to bind and respond to tachynins substance P and neurokinin B/neuromedin-K (By similarity). The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P (By similarity). Substance K binding to its receptor triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol hydrolysis by phospholipase C. Substance K binding also triggers signaling via activation of adenylate cyclase activity which results in increased intracellular levels of cyclic AMP (cAMP) (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Neurokn_rcpt, NK2_rcpt

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 1

• 7XWO EM 2.70A

A predicted model is available from AlphaFold.

Gene Ontology · 21

• GO:0005886 plasma membrane
• GO:0036126 sperm flagellum
• GO:0061827 sperm head
• GO:0097225 sperm midpiece
• GO:0016497 substance K receptor activity
• GO:0004995 tachykinin receptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0014827 intestine smooth muscle contraction
• GO:0006936 muscle contraction
• GO:0033685 negative regulation of luteinizing hormone secretion
• GO:0035106 operant conditioning
• GO:0007209 phospholipase C-activating tachykinin receptor signaling pathway
• GO:0014057 positive regulation of acetylcholine secretion, neurotransmission
• GO:1902093 positive regulation of flagellated sperm motility
• GO:0043270 positive regulation of monoatomic ion transport
• GO:0045987 positive regulation of smooth muscle contraction
• GO:0070474 positive regulation of uterine smooth muscle contraction
• GO:0043117 positive regulation of vascular permeability
• GO:0070459 prolactin secretion
• GO:0051602 response to electrical stimulus
• GO:0007217 tachykinin receptor signaling pathway

Drugs targeting this protein · 3

• NEPADUTANT antagonist
• IBODUTANT antagonist
• SAREDUTANT antagonist

Related proteins · sequence + function similarity

• Substance-K receptor 0.99
• Substance-K receptor 0.99
• Substance-K receptor 0.99
• Substance-K receptor 0.99
• Substance-K receptor 0.99
• Substance-K receptor 0.98
• Substance-K receptor 0.98
• Neuromedin-K receptor 0.89
• Neuromedin-K receptor 0.83
• Neuromedin-K receptor 0.83
• Prolactin-releasing peptide receptor 0.82
• Prolactin-releasing peptide receptor 0.81

Co-cited proteins · studied together in the literature

• Protachykinin-1 1 shared papers
• Substance-P receptor 1 shared papers
• Guanine nucleotide-binding protein G(q) subunit alpha 1 shared papers
• Neuromedin-K receptor 1 shared papers

Literature · 11 cited papers

• Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor. Cell Biosci. · 2023
• Structural insights into the activation of neurokinin 2 receptor by neurokinin A. Cell Discov. · 2022
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Palmitoylation but not the extreme amino-terminus of Gq alpha is required for coupling to the NK2 receptor. FEBS Lett. · 1994
• The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues. J. Biol. Chem. · 1990
• Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis. Cell Growth Differ. · 1991
• PMID 1845990 J. Biol. Chem. · 1991
• Isolation and characterisation of the human lung NK-2 receptor gene using rapid amplification of cDNA ends. Biochem. Biophys. Res. Commun. · 1991
• Cloning, expression of the human substance K receptor, and analysis of its role in mitogenesis. Ann. N. Y. Acad. Sci. · 1991
• Molecular cloning of the human neurokinin-2 receptor cDNA by polymerase chain reaction and isolation of the gene. Ann. N. Y. Acad. Sci. · 1991