Tachykinin receptor 2

TACR2
Identifiers
Aliases	TACR2,NK2R, NKNAR, SKR, TAC2R, Tachykinin receptor 2
External IDs	OMIM:162321;MGI:98477;HomoloGene:55548;GeneCards:TACR2;OMA:TACR2 - orthologs
Gene location (Human) Chr. Chromosome 10 (human) Band 10q22.1 Start 69,403,903bp End 69,416,918bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10|10 B4 Start 62,088,217bp End 62,101,769bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in gastric mucosa muscle layer of sigmoid colon smooth muscle tissue left uterine tube epithelium of colon testicle body of uterus transverse colon fundus myometrium Top expressed in adrenal gland embryo lumbar subsegment of spinal cord right ventricle stomach gastrula colon vastus lateralis muscle tibiofemoral joint duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function tachykinin receptor activity G protein-coupled receptor activity substance K receptor activity signal transducer activity protein binding Cellular component integral component of membrane membrane integral component of plasma membrane sperm flagellum sperm head sperm midpiece plasma membrane Biological process intestine smooth muscle contraction positive regulation of acetylcholine secretion, neurotransmission excretion muscle contraction negative regulation of luteinizing hormone secretion prolactin secretion operant conditioning response to electrical stimulus regulation of uterine smooth muscle contraction positive regulation of vascular permeability positive regulation of ion transport positive regulation of smooth muscle contraction signal transduction positive regulation of uterine smooth muscle contraction tachykinin receptor signaling pathway chemical synaptic transmission positive regulation of flagellated sperm motility G protein-coupled receptor signaling pathway Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 6865 21337 Ensembl ENSG00000075073 ENSMUSG00000020081 UniProt P21452 P30549 RefSeq (mRNA) NM_001057 NM_009314 RefSeq (protein) NP_001048 NP_033340 Location (UCSC) Chr 10: 69.4 – 69.42 Mb Chr 10: 62.09 – 62.1 Mb PubMedsearch
Wikidata
View/Edit Human View/Edit Mouse

Substance-K receptoris aproteinthat in humans is encoded by theTACR2gene.

Function

This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neuropeptide substance K, also referred to as neurokinin A.

Selective Ligands

Several selective ligands for NK₂are now available, and although most of the compounds developed so far are peptides, one small-molecule antagonist Saredutant is currently in clinical trials as ananxiolyticandantidepressant.

Agonists

• GR-64349- potent and selective agonist, EC₅₀3.7nM, 7-amino acid polypeptide chain. CAS# 137593-52-3

Antagonists

• Ibodutant- failed its Phase 3 trial for IBS treatment in 2015, and abandoned by Menarini
• Saredutant- mixed but mostly negative Phase 3 trial results in 2009, and abandoned by Sanofi-Aventis
• GR-159897
• MEN-10376- potent and selective antagonist, 7-amino acid polypeptide chain. CAS# 135306-85-3

See also

• Tachykinin receptor

Further reading

• Maggi CA, Giuliani S, Patacchini R, Santicioli P, Theodorsson E, Barbanti G, Turini D, Giachetti A (Jan 1992). "Tachykinin antagonists inhibit nerve-mediated contractions in the circular muscle of the human ileum. Involvement of neurokinin-2 receptors".Gastroenterology.102(1): 88–96.doi:10.1016/0016-5085(92)91787-5.PMID1370160.
• Gerard NP, Gerard C (1991). "Molecular cloning of the human neurokinin-2 receptor cDNA by polymerase chain reaction and isolation of the gene".Annals of the New York Academy of Sciences.632(1): 389–90.Bibcode:1991NYASA.632..389G.doi:10.1111/j.1749-6632.1991.tb33132.x.PMID1659296.S2CID41610315.
• Cyr C, South V, Saltzman A, Felder S, Ricca GA, Jaye M, Huebner K, Kagan J, Croce CM, Schlessinger J (1991). "Cloning, expression of the human substance K receptor, and analysis of its role in mitogenesis".Annals of the New York Academy of Sciences.632(1): 426–7.Bibcode:1991NYASA.632..426C.doi:10.1111/j.1749-6632.1991.tb33144.x.PMID1659297.S2CID42849825.
• Morten JE, Hopkins B, Powell SJ, Graham A (Dec 1991). "Human NK-2 receptor gene maps to chromosome region 10q11-21".Human Genetics.88(2): 200–3.doi:10.1007/bf00206072.PMID1661704.S2CID328872.
• Graham A, Hopkins B, Powell SJ, Danks P, Briggs I (May 1991). "Isolation and characterisation of the human lung NK-2 receptor gene using rapid amplification of cDNA ends".Biochemical and Biophysical Research Communications.177(1): 8–16.doi:10.1016/0006-291X(91)91940-E.PMID1710456.
• Gerard NP, Eddy RL, Shows TB, Gerard C (Jan 1991)."The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of the cDNA from tracheal and gastric tissues".The Journal of Biological Chemistry.266(2): 1354.doi:10.1016/S0021-9258(17)35323-1.PMID1845990.
• Kris RM, South V, Saltzman A, Felder S, Ricca GA, Jaye M, Huebner K, Kagan J, Croce CM, Schlessinger J (Jan 1991). "Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis".Cell Growth & Differentiation.2(1): 15–22.Bibcode:1991NYASA.632..426C.doi:10.1111/j.1749-6632.1991.tb33144.x.PMID1848773.S2CID42849825.
• Gerard NP, Eddy RL, Shows TB, Gerard C (Nov 1990)."The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues".The Journal of Biological Chemistry.265(33): 20455–62.doi:10.1016/S0021-9258(17)30526-4.PMID2173708.
• Alblas J, van Etten I, Khanum A, Moolenaar WH (Apr 1995)."C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained agonist-induced signaling. Role of receptor phosphorylation in signal attenuation".The Journal of Biological Chemistry.270(15): 8944–51.doi:10.1074/jbc.270.15.8944.PMID7721803.
• Bhogal N, Donnelly D, Findlay JB (Nov 1994)."The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor".The Journal of Biological Chemistry.269(44): 27269–74.doi:10.1016/S0021-9258(18)46979-7.PMID7961636.
• Arkinstall S, Emergy I, Church D, Chollet A, Kawashima E (Jan 1994)."Calcium influx and protein kinase C alpha activation mediate arachidonic acid mobilization by the human NK-2 receptor expressed in Chinese hamster ovary cells".FEBS Letters.338(1): 75–80.doi:10.1016/0014-5793(94)80119-3.PMID8307161.S2CID20900006.
• Brunelleschi S, Bordin G, Colangelo D, Viano I (Jun 1998). "Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis".Neuropeptides.32(3): 215–23.doi:10.1016/S0143-4179(98)90040-3.PMID10189055.S2CID40222022.
• Patacchini R, Giuliani S, Turini A, Navarra G, Maggi CA (Jun 2000). "Effect of nepadutant at tachykinin NK(2) receptors in human intestine and urinary bladder".European Journal of Pharmacology.398(3): 389–97.doi:10.1016/S0014-2999(00)00346-0.PMID10862829.
• Bellucci F, Carini F, Catalani C, Cucchi P, Lecci A, Meini S, Patacchini R, Quartara L, Ricci R, Tramontana M, Giuliani S, Maggi CA (Jan 2002)."Pharmacological profile of the novel mammalian tachykinin, hemokinin 1".British Journal of Pharmacology.135(1): 266–74.doi:10.1038/sj.bjp.0704443.PMC1573107.PMID11786503.
• Patacchini R, Barbagli G, Palminteri E, Lazzeri M, Turini D, Maggi CA (Mar 2002)."Tachykinin NK1 and NK2 receptors mediate inhibitory vs excitatory motor responses in human isolated corpus cavernosum and spongiosum".British Journal of Pharmacology.135(6): 1351–4.doi:10.1038/sj.bjp.0704650.PMC1573278.PMID11906947.
• Candenas ML, Cintado CG, Pennefather JN, Pereda MT, Loizaga JM, Maggi CA, Pinto FM (Dec 2002). "Identification of a tachykinin NK(2) receptor splice variant and its expression in human and rat tissues".Life Sciences.72(3): 269–77.doi:10.1016/S0024-3205(02)02240-3.PMID12427486.
• Bandari PS, Qian J, Oh HS, Potian JA, Yehia G, Harrison JS, Rameshwar P (May 2003). "Crosstalk between neurokinin receptors is relevant to hematopoietic regulation: cloning and characterization of neurokinin-2 promoter".Journal of Neuroimmunology.138(1–2): 65–75.doi:10.1016/S0165-5728(03)00096-1.PMID12742655.S2CID3108613.
• Zhao A, Shea-Donohue T (Oct 2003). "PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors".American Journal of Physiology. Gastrointestinal and Liver Physiology.285(4): G696-703.doi:10.1152/ajpgi.00064.2003.PMID12801882.

External links

• "Tachykinin Receptors: NK₂".IUPHAR Database of Receptors and Ion Channels.International Union of Basic and Clinical Pharmacology. Archived fromthe originalon 2012-05-31.Retrieved2008-12-09.

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.