Substance-P receptor

Function

Receptor for the tachykinin substance P, also able to bind and respond to tachynins neurokinin A/substance K and neurokinin B/neuromedin-K. The rank order of affinity of this receptor to tachykinins is: substance P > neurokinin A/substance K > neurokinin B/neuromedin-K. Substance P binding to its receptor triggers G protein-coupled receptor signaling via activation of phosphatidylinositol hydrolysis by phospholipase C. Substance P 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, NK1_rcpt

Functional cluster

Membrane Transporters & GPCRs

Experimental structures · PDB · 15

• 2KS9 NMR
• 2KSA NMR
• 2KSB NMR
• 6E59 X-ray 3.40A
• 6HLL X-ray 3.27A
• 6HLO X-ray 2.40A
• 6HLP X-ray 2.20A
• 6J20 X-ray 2.70A
• 6J21 X-ray 3.20A
• 7P00 EM 2.71A
• 7P02 EM 2.87A
• 7RMG EM 3.00A
• … and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 51

• GO:0044297 cell body
• GO:0009986 cell surface
• GO:0030425 dendrite
• GO:0005769 early endosome
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0036126 sperm flagellum
• GO:0061827 sperm head
• GO:0097225 sperm midpiece
• GO:0016496 substance P receptor activity
• GO:0004995 tachykinin receptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0002118 aggressive behavior
• GO:0003051 angiotensin-mediated drinking behavior
• GO:0008306 associative learning
• GO:0048266 behavioral response to pain
• GO:0009582 detection of abiotic stimulus
• GO:0042755 eating behavior
• GO:0006954 inflammatory response
• GO:0007616 long-term memory
• GO:0035106 operant conditioning
• GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
• GO:0007209 phospholipase C-activating tachykinin receptor signaling pathway
• GO:0045760 positive regulation of action potential
• GO:0045777 positive regulation of blood pressure
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0010634 positive regulation of epithelial cell migration
• GO:0050679 positive regulation of epithelial cell proliferation
• GO:1902093 positive regulation of flagellated sperm motility
• GO:0046887 positive regulation of hormone secretion
• GO:0002687 positive regulation of leukocyte migration
• GO:0050671 positive regulation of lymphocyte proliferation
• GO:0045778 positive regulation of ossification
• GO:0051496 positive regulation of stress fiber assembly
• GO:0032224 positive regulation of synaptic transmission, cholinergic
• GO:0032230 positive regulation of synaptic transmission, GABAergic
• GO:0070474 positive regulation of uterine smooth muscle contraction
• GO:0043117 positive regulation of vascular permeability
• GO:0045907 positive regulation of vasoconstriction
• GO:0014910 regulation of smooth muscle cell migration
• GO:0048660 regulation of smooth muscle cell proliferation
• GO:0010996 response to auditory stimulus
• GO:0051602 response to electrical stimulus
• GO:0032355 response to estradiol
• GO:0045471 response to ethanol
• GO:0035094 response to nicotine
• GO:0010193 response to ozone
• GO:0032570 response to progesterone
• GO:0060083 smooth muscle contraction involved in micturition
• GO:0042713 sperm ejaculation
• GO:0007217 tachykinin receptor signaling pathway

Drugs targeting this protein · 16

• DNK333 antagonist
• FOSAPREPITANT DIMEGLUMINE antagonist
• APREPITANT antagonist
• CASOPITANT antagonist
• NETUPITANT antagonist
• FIGOPITANT antagonist
• VESTIPITANT MESYLATE antagonist
• ORVEPITANT antagonist
• BURAPITANT antagonist
• TRADIPITANT antagonist
• ROLAPITANT HYDROCHLORIDE antagonist
• FOSNETUPITANT CHLORIDE HYDROCHLORIDE antagonist
• SERLOPITANT antagonist
• ELINZANETANT antagonist
• EZLOPITANT antagonist
• VOFOPITANT antagonist

Related proteins · sequence + function similarity

• Substance-P receptor 1.00
• Substance-P receptor 1.00
• Substance-P receptor 1.00
• Substance-P receptor 1.00
• Substance-P receptor 1.00
• Substance-P receptor 0.94
• Neuromedin-K receptor 0.94
• Neuromedin-K receptor 0.94
• Neuromedin-K receptor 0.90
• Neuromedin-K receptor 0.90
• Neuromedin-K receptor 0.87
• Substance-K receptor 0.83

Co-cited proteins · studied together in the literature

• Neuromedin-K receptor 1 shared papers
• Neuromedin-K receptor 2 shared papers
• Substance-K receptor 1 shared papers

Literature · 13 cited papers

• Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor. Cell Biosci. · 2023
• NMR evidence of GM1-induced conformational change of Substance P using isotropic bicelles. Biochim. Biophys. Acta · 2011
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Identification of single-nucleotide polymorphisms of the human neurokinin 1 receptor gene and pharmacological characterization of a Y192H variant. Pharmacogenomics J. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• The human tachykinin NK1 (short form) and tachykinin NK4 receptor: a reappraisal. Eur. J. Pharmacol. · 2002
• Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345. Nature · 1993
• Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem. Biophys. Res. Commun. · 1991
• Isolation and characterisation of the human lung NK-1 receptor cDNA. Biochem. Biophys. Res. Commun. · 1991
• Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry · 1991
• The primary structure and gene organization of human substance P and neuromedin K receptors. Eur. J. Biochem. · 1992
• … and 1 more in the literature graph