Neuromedin-K receptor

UniProt P29371 Organism Homo sapiens Gene NK3R, TAC3R, TACR3

Also known as: NK3R, TAC3R, TACR3

Function

Receptor for the tachykinin neuromedin-K (neurokinin B), also able to bind and respond to tachynins substance K/neurokinin A and substance P. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K and substance P. Neuromedin-K binding to its receptor triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol hydrolysis by phospholipase C. Neuromedin-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, NK3_rcpt
Functional cluster: Membrane Transporters & GPCRs

Experimental structures · PDB · 3

8JBF EM 3.00A
8JBG EM 2.80A
8JBH EM 2.90A

A predicted model is available from AlphaFold.

Gene Ontology · 23

Disease associations

hypogonadotropic hypogonadism 11 with or without anosmia MONDO:0013913

Drugs targeting this protein · 4

TALNETANT antagonist
PAVINETANT antagonist
FEZOLINETANT antagonist
ELINZANETANT antagonist

Related proteins · sequence + function similarity

Neuromedin-K receptor 0.99
Neuromedin-K receptor 0.97
Neuromedin-K receptor 0.97
Neuromedin-K receptor 0.93
Substance-P receptor 0.91
Substance-P receptor 0.91
Substance-P receptor 0.91
Substance-P receptor 0.91
Substance-P receptor 0.90
Substance-P receptor 0.90
Tachykinin-like peptides receptor 99D 0.90
Substance-P receptor 0.89

Co-cited proteins · studied together in the literature

Tachykinin-3 3 shared papers
Substance-P receptor 2 shared papers
Substance-K receptor 1 shared papers
Protachykinin-1 1 shared papers
Gonadotropin-releasing hormone receptor 2 shared papers
Prokineticin-2 2 shared papers
Prokineticin receptor 2 2 shared papers
Anosmin-1 2 shared papers
Heparan-sulfate 6-O-sulfotransferase 1 1 shared papers
Semaphorin-3A 1 shared papers
Transcription factor SOX-10 1 shared papers
Interleukin-17 receptor D 1 shared papers

Literature · 9 cited papers

Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor. Cell Biosci. · 2023
Structural insights into neurokinin 3 receptor activation by endogenous and analogue peptide agonists. Cell Discov. · 2023
The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J. Clin. Endocrinol. Metab. · 2014
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am. J. Hum. Genet. · 2013
TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat. Genet. · 2009
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
cDNA sequence and heterologous expression of the human neurokinin-3 receptor. Biochem. Biophys. Res. Commun. · 1992
The primary structure and gene organization of human substance P and neuromedin K receptors. Eur. J. Biochem. · 1992
Molecular characterisation, expression and localisation of human neurokinin-3 receptor. FEBS Lett. · 1992

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