NK2R_HUMAN
ID NK2R_HUMAN Reviewed; 398 AA.
AC P21452; A8K7I1; Q4QRI5; Q8NGQ8; Q9UDE6; Q9UDE7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Substance-K receptor;
DE Short=SKR;
DE AltName: Full=NK-2 receptor;
DE Short=NK-2R;
DE AltName: Full=Neurokinin A receptor;
DE AltName: Full=Tachykinin receptor 2;
GN Name=TACR2; Synonyms=NK2R, NKNAR, TAC2R;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT LYS-245.
RC TISSUE=Stomach, and Trachea;
RX PubMed=2173708; DOI=10.1016/s0021-9258(17)30526-4;
RA Gerard N.P., Eddy R.L. Jr., Shows T.B., Gerard C.;
RT "The human neurokinin A (substance K) receptor. Molecular cloning of the
RT gene, chromosome localization, and isolation of cDNA from tracheal and
RT gastric tissues.";
RL J. Biol. Chem. 265:20455-20462(1990).
RN [2]
RP ERRATUM OF PUBMED:2173708.
RX PubMed=1845990; DOI=10.1016/s0021-9258(17)35323-1;
RA Gerard N.P., Eddy R.L. Jr., Shows T.B., Gerard C.;
RL J. Biol. Chem. 266:1354-1354(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1659296; DOI=10.1111/j.1749-6632.1991.tb33132.x;
RA Gerard N.P., Gerard C.;
RT "Molecular cloning of the human neurokinin-2 receptor cDNA by polymerase
RT chain reaction and isolation of the gene.";
RL Ann. N. Y. Acad. Sci. 632:389-390(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANTS THR-23 AND LYS-245.
RC TISSUE=Jejunum;
RX PubMed=1659297; DOI=10.1111/j.1749-6632.1991.tb33144.x;
RA Cyr C., South V., Saltzman A., Felder S., Ricca G.A., Jaye M., Huebner K.,
RA Kagan J., Croce C.M., Schlessinger J.;
RT "Cloning, expression of the human substance K receptor, and analysis of its
RT role in mitogenesis.";
RL Ann. N. Y. Acad. Sci. 632:426-427(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-23 AND LYS-245.
RC TISSUE=Lung;
RX PubMed=1710456; DOI=10.1016/0006-291x(91)91940-e;
RA Graham A., Hopkins B., Powell S.J., Danks P., Briggs I.;
RT "Isolation and characterisation of the human lung NK-2 receptor gene using
RT rapid amplification of cDNA ends.";
RL Biochem. Biophys. Res. Commun. 177:8-16(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-375.
RX PubMed=1848773;
RA Kris R.M., South V., Saltzman A., Felder S., Ricca G.A., Jaye M.,
RA Huebner K., Kagan J., Croce C.M., Schlessinger J.;
RT "Cloning and expression of the human substance K receptor and analysis of
RT its role in mitogenesis.";
RL Cell Growth Differ. 2:15-22(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-245.
RC TISSUE=Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-245.
RC TISSUE=Stomach;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LYS-245.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-245.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: This is a receptor for the tachykinin neuropeptide substance
CC K (neurokinin A). It is associated with G proteins that activate a
CC phosphatidylinositol-calcium second messenger system. The rank order of
CC affinity of this receptor to tachykinins is: substance K > neuromedin-K
CC > substance P. {ECO:0000269|PubMed:1659297}.
CC -!- INTERACTION:
CC P21452; PRO_0000033534 [P20366]: TAC1; NbExp=2; IntAct=EBI-6655413, EBI-6655449;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M57414; AAC31760.1; -; mRNA.
DR EMBL; M60284; AAA60347.1; -; Genomic_DNA.
DR EMBL; M57415; AAA60347.1; JOINED; Genomic_DNA.
DR EMBL; M60281; AAA60347.1; JOINED; Genomic_DNA.
DR EMBL; M60282; AAA60347.1; JOINED; Genomic_DNA.
DR EMBL; M60283; AAA60347.1; JOINED; Genomic_DNA.
DR EMBL; M75105; AAB05897.1; -; Genomic_DNA.
DR EMBL; M75101; AAB05897.1; JOINED; Genomic_DNA.
DR EMBL; M75102; AAB05897.1; JOINED; Genomic_DNA.
DR EMBL; M75103; AAB05897.1; JOINED; Genomic_DNA.
DR EMBL; M75104; AAB05897.1; JOINED; Genomic_DNA.
DR EMBL; AB065731; BAC05952.1; -; Genomic_DNA.
DR EMBL; AK291996; BAF84685.1; -; mRNA.
DR EMBL; AY322545; AAP84358.1; -; mRNA.
DR EMBL; CH471083; EAW54324.1; -; Genomic_DNA.
DR EMBL; BC096842; AAH96842.1; -; mRNA.
DR CCDS; CCDS7293.1; -.
DR PIR; JQ1059; JQ1059.
DR RefSeq; NP_001048.2; NM_001057.2.
DR AlphaFoldDB; P21452; -.
DR SMR; P21452; -.
DR BioGRID; 112728; 4.
DR ELM; P21452; -.
DR IntAct; P21452; 1.
DR STRING; 9606.ENSP00000362403; -.
DR BindingDB; P21452; -.
DR ChEMBL; CHEMBL2327; -.
DR DrugBank; DB06660; Saredutant.
DR DrugCentral; P21452; -.
DR GuidetoPHARMACOLOGY; 361; -.
DR GlyGen; P21452; 2 sites.
DR iPTMnet; P21452; -.
DR PhosphoSitePlus; P21452; -.
DR BioMuta; TACR2; -.
DR DMDM; 229462950; -.
DR MassIVE; P21452; -.
DR PaxDb; P21452; -.
DR PeptideAtlas; P21452; -.
DR PRIDE; P21452; -.
DR ProteomicsDB; 53870; -.
DR Antibodypedia; 1518; 310 antibodies from 36 providers.
DR DNASU; 6865; -.
DR Ensembl; ENST00000373306.5; ENSP00000362403.4; ENSG00000075073.16.
DR GeneID; 6865; -.
DR KEGG; hsa:6865; -.
DR MANE-Select; ENST00000373306.5; ENSP00000362403.4; NM_001057.3; NP_001048.2.
DR UCSC; uc001jpn.3; human.
DR CTD; 6865; -.
DR DisGeNET; 6865; -.
DR GeneCards; TACR2; -.
DR HGNC; HGNC:11527; TACR2.
DR HPA; ENSG00000075073; Tissue enhanced (intestine, stomach).
DR MIM; 162321; gene.
DR neXtProt; NX_P21452; -.
DR OpenTargets; ENSG00000075073; -.
DR PharmGKB; PA36303; -.
DR VEuPathDB; HostDB:ENSG00000075073; -.
DR eggNOG; KOG4219; Eukaryota.
DR GeneTree; ENSGT00940000155512; -.
DR InParanoid; P21452; -.
DR OMA; RRVNRCH; -.
DR OrthoDB; 715197at2759; -.
DR PhylomeDB; P21452; -.
DR TreeFam; TF315303; -.
DR PathwayCommons; P21452; -.
DR Reactome; R-HSA-380095; Tachykinin receptors bind tachykinins.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P21452; -.
DR SIGNOR; P21452; -.
DR BioGRID-ORCS; 6865; 14 hits in 1070 CRISPR screens.
DR ChiTaRS; TACR2; human.
DR GeneWiki; Tachykinin_receptor_2; -.
DR GenomeRNAi; 6865; -.
DR Pharos; P21452; Tchem.
DR PRO; PR:P21452; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P21452; protein.
DR Bgee; ENSG00000075073; Expressed in mucosa of stomach and 111 other tissues.
DR ExpressionAtlas; P21452; baseline and differential.
DR Genevisible; P21452; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0036126; C:sperm flagellum; IDA:UniProtKB.
DR GO; GO:0061827; C:sperm head; IDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0016497; F:substance K receptor activity; IBA:GO_Central.
DR GO; GO:0004995; F:tachykinin receptor activity; IBA:GO_Central.
DR GO; GO:0014827; P:intestine smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0033685; P:negative regulation of luteinizing hormone secretion; IEA:Ensembl.
DR GO; GO:0035106; P:operant conditioning; IEA:Ensembl.
DR GO; GO:0014057; P:positive regulation of acetylcholine secretion, neurotransmission; IEA:Ensembl.
DR GO; GO:1902093; P:positive regulation of flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; TAS:ProtInc.
DR GO; GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0043117; P:positive regulation of vascular permeability; IEA:Ensembl.
DR GO; GO:0070459; P:prolactin secretion; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; TAS:ProtInc.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001681; Neurokn_rcpt.
DR InterPro; IPR000913; NK2_rcpt.
DR PANTHER; PTHR46925:SF3; PTHR46925:SF3; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01025; NEUROKININ2R.
DR PRINTS; PR00244; NEUROKININR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..398
FT /note="Substance-K receptor"
FT /id="PRO_0000069893"
FT TOPO_DOM 1..32
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 33..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..107
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..129
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..196
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..218
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..290
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..310
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 311..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT LIPID 324
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 106..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 23
FT /note="I -> T (in dbSNP:rs5030920)"
FT /evidence="ECO:0000269|PubMed:1659297,
FT ECO:0000269|PubMed:1710456"
FT /id="VAR_016159"
FT VARIANT 47
FT /note="A -> T (in dbSNP:rs57500981)"
FT /id="VAR_061221"
FT VARIANT 245
FT /note="M -> K (in dbSNP:rs55953810)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1659297,
FT ECO:0000269|PubMed:1710456, ECO:0000269|PubMed:2173708,
FT ECO:0000269|Ref.10, ECO:0000269|Ref.9"
FT /id="VAR_061222"
FT VARIANT 363
FT /note="T -> A (in dbSNP:rs57900755)"
FT /id="VAR_061223"
FT VARIANT 375
FT /note="R -> H (in dbSNP:rs2229170)"
FT /evidence="ECO:0000269|PubMed:1848773"
FT /id="VAR_014680"
FT VARIANT 395
FT /note="H -> R (in dbSNP:rs58692969)"
FT /id="VAR_061224"
FT CONFLICT 38
FT /note="T -> P (in Ref. 1; AAC31760/AAA60347)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="Y -> V (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="L -> P (in Ref. 11; AAH96842)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="F -> FF (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="P -> R (in Ref. 11; AAH96842)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 398 AA; 44442 MW; 20AD618EF74263A7 CRC64;
MGTCDIVTEA NISSGPESNT TGITAFSMPS WQLALWATAY LALVLVAVTG NAIVIWIILA
HRRMRTVTNY FIVNLALADL CMAAFNAAFN FVYASHNIWY FGRAFCYFQN LFPITAMFVS
IYSMTAIAAD RYMAIVHPFQ PRLSAPSTKA VIAGIWLVAL ALASPQCFYS TVTMDQGATK
CVVAWPEDSG GKTLLLYHLV VIALIYFLPL AVMFVAYSVI GLTLWRRAVP GHQAHGANLR
HLQAMKKFVK TMVLVVLTFA ICWLPYHLYF ILGSFQEDIY CHKFIQQVYL ALFWLAMSST
MYNPIIYCCL NHRFRSGFRL AFRCCPWVTP TKEDKLELTP TTSLSTRVNR CHTKETLFMA
GDTAPSEATS GEAGRPQDGS GLWFGYGLLA PTKTHVEI
