ID   TKN1_HUMAN              Reviewed;         129 AA.
AC   P20366; O60600; O60601; Q00072; Q53GH4; Q549V0; Q549V1; Q549V2; Q6FHM1;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   02-SEP-2026, entry version 222.
DE   RecName: Full=Protachykinin-1;
DE   AltName: Full=PPT;
DE   Contains:
DE     RecName: Full=Substance P {ECO:0000303|PubMed:6208535};
DE   Contains:
DE     RecName: Full=Neurokinin A;
DE              Short=NKA;
DE     AltName: Full=Neuromedin L;
DE     AltName: Full=Substance K;
DE   Contains:
DE     RecName: Full=Neuropeptide K;
DE              Short=NPK;
DE   Contains:
DE     RecName: Full=Neuropeptide gamma;
DE   Contains:
DE     RecName: Full=C-terminal-flanking peptide;
DE   Flags: Precursor;
GN   Name=TAC1; Synonyms=NKA, NKNA, TAC2;
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 [MRNA] (ISOFORM BETA), AND AMIDATION AT MET-68 AND
RP   MET-107.
RX   PubMed=3770210; DOI=10.1016/0014-5793(86)81534-4;
RA   Harmar A.J., Armstrong A., Pascall J.C., Chapman K., Rosie R., Curtis A.,
RA   Going J., Edwards C.R.W., Fink G.;
RT   "cDNA sequence of human beta-preprotachykinin, the common precursor to
RT   substance P and neurokinin A.";
RL   FEBS Lett. 208:67-72(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC   TISSUE=Brain;
RA   Tan A., Too H.P.;
RL   Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC   TISSUE=Small intestine;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
RC   TISSUE=Brain;
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).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 36-122 (ISOFORMS BETA AND GAMMA).
RC   TISSUE=Testis;
RX   PubMed=1708336; DOI=10.1210/endo-128-5-2441;
RA   Chiwakata C., Brackmann B., Hunt N., Davidoff M., Schulze W., Ivell R.;
RT   "Tachykinin (substance-P) gene expression in Leydig cells of the human and
RT   mouse testis.";
RL   Endocrinology 128:2441-2448(1991).
RN   [10]
RP   PROTEIN SEQUENCE OF 98-107, AND AMIDATION AT MET-107.
RX   PubMed=3038549; DOI=10.1111/j.1432-1033.1987.tb13567.x;
RA   Theodorsson-Norheim E., Joernvall H., Andersson M., Norheim I., Oeberg K.,
RA   Jacobsson G.;
RT   "Isolation and characterization of neurokinin A, neurokinin A(3-10) and
RT   neurokinin A(4-10) from a neutral water extract of a metastatic ileal
RT   carcinoid tumour.";
RL   Eur. J. Biochem. 166:693-697(1987).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 36-122 (ISOFORMS ALPHA; BETA AND DELTA).
RC   TISSUE=Blood, and Brain;
RX   PubMed=9846828; DOI=10.1016/s0165-5728(98)00170-2;
RA   Lai J.P., Douglas S.D., Rappaport E., Wu J.M., Ho W.Z.;
RT   "Identification of a delta isoform of preprotachykinin mRNA in human
RT   mononuclear phagocytes and lymphocytes.";
RL   J. Neuroimmunol. 91:121-128(1998).
RN   [12]
RP   PROTEIN SEQUENCE OF 111-126.
RC   TISSUE=Adrenal medulla;
RX   PubMed=2284201; DOI=10.1016/0196-9781(90)90007-r;
RA   McGregor G.P., Conlon J.M.;
RT   "Characterization of the C-terminal flanking peptide of human beta-
RT   preprotachykinin.";
RL   Peptides 11:907-910(1990).
RN   [13]
RP   CLEAVAGE BY ACE AND MME.
RX   PubMed=6208535; DOI=10.1016/0196-9781(84)90020-2;
RA   Skidgel R.A., Engelbrecht S., Johnson A.R., Erdoes E.G.;
RT   "Hydrolysis of substance p and neurotensin by converting enzyme and neutral
RT   endopeptidase.";
RL   Peptides 5:769-776(1984).
RN   [14]
RP   SUBCELLULAR LOCATION (SUBSTANCE P), CLEAVAGE BY FAP, AND CLEAVAGE SITE.
RX   PubMed=21314817; DOI=10.1111/j.1742-4658.2011.08051.x;
RA   Keane F.M., Nadvi N.A., Yao T.W., Gorrell M.D.;
RT   "Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY are
RT   novel substrates of fibroblast activation protein-alpha.";
RL   FEBS J. 278:1316-1332(2011).
RN   [15]
RP   FUNCTION (SUBSTANCE P).
RX   PubMed=30686732; DOI=10.1016/j.neuron.2019.01.012;
RA   Green D.P., Limjunyawong N., Gour N., Pundir P., Dong X.;
RT   "A mast-cell-specific receptor mediates neurogenic inflammation and pain.";
RL   Neuron 101:412-420(2019).
RN   [16]
RP   STRUCTURE BY NMR OF 72-107.
RX   PubMed=16503654; DOI=10.1021/bi052287o;
RA   Dike A., Cowsik S.M.;
RT   "Three-dimensional structure of neuropeptide K bound to
RT   dodecylphosphocholine micelles.";
RL   Biochemistry 45:2994-3004(2006).
RN   [17] {ECO:0007744|PDB:7VDM}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.76 ANGSTROMS) OF 58-68 IN COMPLEX WITH
RP   MRGPRX2; GNAI1; GNB1 AND GNG2, FUNCTION (SUBSTANCE P), AND SUBCELLULAR
RP   LOCATION (SUBSTANCE P).
RX   PubMed=34789875; DOI=10.1038/s41586-021-04077-y;
RA   Yang F., Guo L., Li Y., Wang G., Wang J., Zhang C., Fang G.X., Chen X.,
RA   Liu L., Yan X., Liu Q., Qu C., Xu Y., Xiao P., Zhu Z., Li Z., Zhou J.,
RA   Yu X., Gao N., Sun J.P.;
RT   "Structure, function and pharmacology of human itch receptor complexes.";
RL   Nature 600:164-169(2021).
RN   [18] {ECO:0007744|PDB:7XWO}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) OF 98-107 IN COMPLEX WITH
RP   TACR2 AND GNAQ, AND FUNCTION (NEUROKININ A).
RX   PubMed=35882833; DOI=10.1038/s41421-022-00437-8;
RA   Sun W., Yuan Q., Zhang H., Yang F., Ling S., Luo Y., Lv P., Eric Xu H.,
RA   Tian C., Yin W., Shi P.;
RT   "Structural insights into the activation of neurokinin 2 receptor by
RT   neurokinin A.";
RL   Cell Discov. 8:72-72(2022).
RN   [19] {ECO:0007744|PDB:8JBH}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 58-68 IN COMPLEX WITH
RP   TACR3 AND GNAQ, AND FUNCTION (SUBSTANCE P).
RX   PubMed=37391393; DOI=10.1038/s41421-023-00564-w;
RA   Sun W., Yang F., Zhang H., Yuan Q., Ling S., Wang Y., Lv P., Li Z., Luo Y.,
RA   Liu D., Yin W., Shi P., Xu H.E., Tian C.;
RT   "Structural insights into neurokinin 3 receptor activation by endogenous
RT   and analogue peptide agonists.";
RL   Cell Discov. 9:66-66(2023).
CC   -!- FUNCTION: Tachykinins are active peptides which excite neurons, evoke
CC       behavioral responses, are potent vasodilators and secretagogues, and
CC       contract (directly or indirectly) many smooth muscles.
CC   -!- FUNCTION: [Substance P]: Is a ligand for TACR1, and triggers G protein-
CC       coupled receptor signaling via activation of phosphatidylinositol
CC       hydrolysis by phospholipase C. Substance P binding to TACR1 also
CC       triggers signaling via activation of adenylate cyclase activity which
CC       results in increased intracellular levels of cyclic AMP (cAMP) (By
CC       similarity). Is also a TACR3 agonist with low receptor affinity
CC       (PubMed:37391393). Basic secretagogue neuropeptide released from the
CC       terminals of specific sensory nerves (PubMed:30686732). Acts as a
CC       ligand for MRGPRX2 receptor in mast cells, initiating a signaling that
CC       mediates neurogenic inflammation and pain (PubMed:30686732,
CC       PubMed:34789875). Neurogenic inflammation includes mast cell
CC       activation, recruitment of immune cells and release of inflammatory
CC       mediators, such as cytokines and chemokines (By similarity). The
CC       inflammatory response can then activate or sensitize nociceptors,
CC       promoting pain (By similarity). {ECO:0000250|UniProtKB:P06767,
CC       ECO:0000250|UniProtKB:P41539, ECO:0000269|PubMed:30686732,
CC       ECO:0000269|PubMed:34789875, ECO:0000269|PubMed:37391393}.
CC   -!- FUNCTION: [Neurokinin A]: Is a ligand for TACR2, and triggers G
CC       protein-coupled receptor signaling via activation of G(q) and
CC       phosphatidylinositol hydrolysis by phospholipase C (PubMed:35882833).
CC       Binding to TACR2 also triggers signaling via activation of adenylate
CC       cyclase activity which results in increased intracellular levels of
CC       cyclic AMP (cAMP). {ECO:0000250|UniProtKB:P06767,
CC       ECO:0000269|PubMed:35882833}.
CC   -!- INTERACTION:
CC       PRO_0000033530; P25103: TACR1; NbExp=2; IntAct=EBI-6655360, EBI-6655287;
CC       PRO_0000033534; P21452: TACR2; NbExp=2; IntAct=EBI-6655449, EBI-6655413;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SUBCELLULAR LOCATION: [Substance P]: Secreted
CC       {ECO:0000269|PubMed:21314817, ECO:0000269|PubMed:34789875}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=Beta;
CC         IsoId=P20366-1; Sequence=Displayed;
CC       Name=Alpha;
CC         IsoId=P20366-2; Sequence=VSP_006376, VSP_006377;
CC       Name=Gamma;
CC         IsoId=P20366-3; Sequence=VSP_006375;
CC       Name=Delta;
CC         IsoId=P20366-4; Sequence=VSP_006375, VSP_006376, VSP_006377;
CC   -!- PTM: [Substance P]: The substance P form is cleaved at Pro-59 by the
CC       prolyl endopeptidase FAP (seprase) activity (in vitro)
CC       (PubMed:21314817). Substance P is also cleaved and degraded by
CC       Angiotensin-converting enzyme (ACE) and neprilysin (MME)
CC       (PubMed:6208535). {ECO:0000269|PubMed:21314817,
CC       ECO:0000269|PubMed:6208535}.
CC   -!- SIMILARITY: Belongs to the tachykinin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Neurokinin-1 entry;
CC       URL="https://en.wikipedia.org/wiki/Neurokinin_1";
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/44483/TAC1";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X54469; CAA38351.1; -; mRNA.
DR   EMBL; U37529; AAA79195.1; -; mRNA.
DR   EMBL; CR407602; CAG28529.1; -; mRNA.
DR   EMBL; CR541730; CAG46531.1; -; mRNA.
DR   EMBL; AK222957; BAD96677.1; -; mRNA.
DR   EMBL; AC004140; AAQ96888.1; -; Genomic_DNA.
DR   EMBL; AC004140; AAQ96889.1; -; Genomic_DNA.
DR   EMBL; AC004140; AAQ96890.1; -; Genomic_DNA.
DR   EMBL; AC004140; AAQ96891.1; -; Genomic_DNA.
DR   EMBL; CH236949; EAL24116.1; -; Genomic_DNA.
DR   EMBL; CH236949; EAL24117.1; -; Genomic_DNA.
DR   EMBL; CH236949; EAL24118.1; -; Genomic_DNA.
DR   EMBL; CH236949; EAL24119.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76734.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76735.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76736.1; -; Genomic_DNA.
DR   EMBL; CH471091; EAW76737.1; -; Genomic_DNA.
DR   EMBL; BC018047; AAH18047.1; -; mRNA.
DR   EMBL; M68906; AAA60159.1; -; mRNA.
DR   EMBL; M68907; AAA60160.1; -; mRNA.
DR   EMBL; AF050655; AAC15701.1; -; mRNA.
DR   EMBL; AF050656; AAC15702.1; -; mRNA.
DR   EMBL; AF050658; AAC15704.1; -; mRNA.
DR   CCDS; CCDS5649.1; -. [P20366-1]
DR   CCDS; CCDS5650.1; -. [P20366-2]
DR   CCDS; CCDS5651.1; -. [P20366-3]
DR   PIR; A24805; SPHUB.
DR   RefSeq; NP_003173.1; NM_003182.3. [P20366-1]
DR   RefSeq; NP_054702.1; NM_013996.3. [P20366-2]
DR   RefSeq; NP_054703.1; NM_013997.3. [P20366-3]
DR   RefSeq; NP_054704.1; NM_013998.3. [P20366-4]
DR   PDB; 2B19; NMR; -; A=72-107.
DR   PDB; 2KS9; NMR; -; B=58-68.
DR   PDB; 2KSA; NMR; -; B=58-68.
DR   PDB; 2KSB; NMR; -; B=58-68.
DR   PDB; 4HOM; X-ray; 1.90 A; B=58-68.
DR   PDB; 7P00; EM; 2.71 A; P=58-68.
DR   PDB; 7P02; EM; 2.87 A; P=58-68.
DR   PDB; 7RMG; EM; 3.00 A; S=58-68.
DR   PDB; 7RMH; EM; 3.10 A; S=58-68.
DR   PDB; 7VDM; EM; 2.98 A; L=58-68.
DR   PDB; 7XWO; EM; 2.70 A; D=98-107.
DR   PDB; 8JBH; EM; 2.90 A; A=58-68.
DR   PDB; 8U26; EM; 2.50 A; S=58-68.
DR   AlphaFoldDB; P20366; -.
DR   EMDB; EMD-13140; -.
DR   EMDB; EMD-13141; -.
DR   EMDB; EMD-24569; -.
DR   EMDB; EMD-24570; -.
DR   EMDB; EMD-31923; -.
DR   EMDB; EMD-36146; -.
DR   EMDB; EMD-41840; -.
DR   MDposit; P20366; -.
DR   MDRepo; P20366; -.
DR   SMR; P20366; -.
DR   BioGRID; 112727; 8.
DR   FunCoup; P20366; 695.
DR   IntAct; P20366; 13.
DR   MINT; P20366; -.
DR   NDEx; IQUERY-CP-TAC1; 1 NDEx IQuery Curated Pathway.
DR   STRING; 9606.ENSP00000321106; -.
DR   BindingDB; P20366; -.
DR   PhosphoSitePlus; P20366; -.
DR   BioMuta; TAC1; -.
DR   DMDM; 135886; -.
DR   jPOST; P20366; -.
DR   MassIVE; P20366; -.
DR   PaxDb; 9606-ENSP00000321106; -.
DR   PeptideAtlas; P20366; -.
DR   ProteomicsDB; 53754; -. [P20366-1]
DR   ProteomicsDB; 53755; -. [P20366-2]
DR   ProteomicsDB; 53756; -. [P20366-3]
DR   ProteomicsDB; 53757; -. [P20366-4]
DR   Antibodypedia; 2784; 607 antibodies from 42 providers.
DR   DNASU; 6863; -.
DR   Ensembl; ENST00000319273.10; ENSP00000321106.5; ENSG00000006128.13. [P20366-1]
DR   Ensembl; ENST00000346867.4; ENSP00000289574.4; ENSG00000006128.13. [P20366-3]
DR   Ensembl; ENST00000350485.8; ENSP00000289576.4; ENSG00000006128.13. [P20366-2]
DR   Ensembl; ENST00000864055.1; ENSP00000534114.1; ENSG00000006128.13. [P20366-4]
DR   Ensembl; ENST00000926836.1; ENSP00000596895.1; ENSG00000006128.13. [P20366-1]
DR   Ensembl; ENST00000962701.1; ENSP00000632760.1; ENSG00000006128.13. [P20366-1]
DR   GeneID; 6863; -.
DR   KEGG; hsa:6863; -.
DR   MANE-Select; ENST00000319273.10; ENSP00000321106.5; NM_003182.3; NP_003173.1.
DR   UCSC; uc003uop.5; human. [P20366-1]
DR   AGR; HGNC:11517; -.
DR   ClinPGx; PA36297; -.
DR   CTD; 6863; -.
DR   DisGeNET; 6863; -.
DR   GeneCards; TAC1; -.
DR   HGNC; HGNC:11517; TAC1.
DR   HPA; ENSG00000006128; Tissue enriched (brain).
DR   MIM; 162320; gene.
DR   OpenTargets; ENSG00000006128; -.
DR   VEuPathDB; HostDB:ENSG00000006128; -.
DR   eggNOG; ENOG502S1KJ; Eukaryota.
DR   GeneTree; ENSGT00390000002457; -.
DR   HOGENOM; CLU_149426_0_0_1; -.
DR   InParanoid; P20366; -.
DR   OMA; GQMSHKR; -.
DR   OrthoDB; 9936276at2759; -.
DR   PAN-GO; P20366; 5 GO annotations based on evolutionary models.
DR   PhylomeDB; P20366; -.
DR   PathwayCommons; P20366; -.
DR   Reactome; R-HSA-380095; Tachykinin receptors bind tachykinins.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   SignaLink; P20366; -.
DR   SIGNOR; P20366; -.
DR   Agora; ENSG00000006128; -.
DR   BioGRID-ORCS; 6863; 10 hits in 1139 CRISPR screens.
DR   EvolutionaryTrace; P20366; -.
DR   GeneWiki; TAC1; -.
DR   GenomeRNAi; 6863; -.
DR   Pharos; P20366; Tbio.
DR   PRO; PR:P20366; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P20366; protein.
DR   Bgee; ENSG00000006128; Expressed in dorsal root ganglion and 143 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IEA:Ensembl.
DR   GO; GO:0031835; F:substance P receptor binding; IBA:GO_Central.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0009582; P:detection of abiotic stimulus; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0007320; P:insemination; TAS:ProtInc.
DR   GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR   GO; GO:0010459; P:negative regulation of heart rate; IEA:Ensembl.
DR   GO; GO:0007209; P:phospholipase C-activating tachykinin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0045760; P:positive regulation of action potential; IEA:Ensembl.
DR   GO; GO:0002675; P:positive regulation of acute inflammatory response; IEA:Ensembl.
DR   GO; GO:2000854; P:positive regulation of corticosterone secretion; IEA:Ensembl.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR   GO; GO:0010634; P:positive regulation of epithelial cell migration; IEA:Ensembl.
DR   GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IEA:Ensembl.
DR   GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl.
DR   GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
DR   GO; GO:0032224; P:positive regulation of synaptic transmission, cholinergic; IEA:Ensembl.
DR   GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0007217; P:tachykinin receptor signaling pathway; IBA:GO_Central.
DR   InterPro; IPR013055; Tachy_Neuro_lke_CS.
DR   InterPro; IPR008215; Tachykinin_dom.
DR   InterPro; IPR008216; Tachykinin_fam.
DR   PANTHER; PTHR11250:SF3; PROTACHYKININ-1; 1.
DR   PANTHER; PTHR11250; TACHYKININ; 1.
DR   Pfam; PF30908; Neurokinin_A; 1.
DR   Pfam; PF02202; Tachykinin; 1.
DR   PRINTS; PR01829; PROTACHYKNIN.
DR   SMART; SM00203; TK; 2.
DR   PROSITE; PS00267; TACHYKININ; 2.
DR   PDBsum; 2B19; -.
DR   PDBsum; 2KS9; -.
DR   PDBsum; 2KSA; -.
DR   PDBsum; 2KSB; -.
DR   PDBsum; 4HOM; -.
DR   PDBsum; 7P00; -.
DR   PDBsum; 7P02; -.
DR   PDBsum; 7RMG; -.
DR   PDBsum; 7RMH; -.
DR   PDBsum; 7VDM; -.
DR   PDBsum; 7XWO; -.
DR   PDBsum; 8JBH; -.
DR   PDBsum; 8U26; -.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Amidation;
KW   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Neuropeptide; Neurotransmitter; Proteomics identification;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..56
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033529"
FT   PEPTIDE         58..68
FT                   /note="Substance P"
FT                   /id="PRO_0000033530"
FT   PEPTIDE         72..107
FT                   /note="Neuropeptide K"
FT                   /id="PRO_0000033531"
FT   PEPTIDE         72..73
FT                   /note="Neuropeptide gamma, 1st part"
FT                   /id="PRO_0000033532"
FT   PEPTIDE         89..107
FT                   /note="Neuropeptide gamma, 2nd part"
FT                   /id="PRO_0000033533"
FT   PEPTIDE         98..107
FT                   /note="Neurokinin A"
FT                   /id="PRO_0000033534"
FT   PEPTIDE         111..126
FT                   /note="C-terminal-flanking peptide"
FT                   /id="PRO_0000033535"
FT   SITE            59..60
FT                   /note="Cleavage; by FAP"
FT                   /evidence="ECO:0000269|PubMed:21314817"
FT   SITE            63..64
FT                   /note="Cleavage; by MME"
FT                   /evidence="ECO:0000269|PubMed:6208535"
FT   SITE            64..65
FT                   /note="Cleavage; by MME"
FT                   /evidence="ECO:0000269|PubMed:6208535"
FT   SITE            65..66
FT                   /note="Cleavage; by ACE"
FT                   /evidence="ECO:0000269|PubMed:6208535"
FT   SITE            66..67
FT                   /note="Cleavage; by ACE and MME"
FT                   /evidence="ECO:0000269|PubMed:6208535"
FT   MOD_RES         68
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000269|PubMed:3770210"
FT   MOD_RES         107
FT                   /note="Methionine amide"
FT                   /evidence="ECO:0000269|PubMed:3038549,
FT                   ECO:0000269|PubMed:3770210"
FT   VAR_SEQ         74..88
FT                   /note="Missing (in isoform Gamma and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:1708336,
FT                   ECO:0000303|PubMed:9846828"
FT                   /id="VSP_006375"
FT   VAR_SEQ         97..114
FT                   /note="Missing (in isoform Alpha and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:9846828"
FT                   /id="VSP_006376"
FT   VAR_SEQ         115
FT                   /note="V -> M (in isoform Alpha and isoform Delta)"
FT                   /evidence="ECO:0000303|PubMed:9846828"
FT                   /id="VSP_006377"
FT   CONFLICT        32
FT                   /note="S -> P (in Ref. 4; BAD96677)"
FT                   /evidence="ECO:0000305"
FT   HELIX           59..62
FT                   /evidence="ECO:0007829|PDB:2KS9"
FT   TURN            64..66
FT                   /evidence="ECO:0007829|PDB:2KS9"
FT   HELIX           73..80
FT                   /evidence="ECO:0007829|PDB:2B19"
FT   HELIX           81..88
FT                   /evidence="ECO:0007829|PDB:2B19"
FT   HELIX           89..91
FT                   /evidence="ECO:0007829|PDB:2B19"
FT   HELIX           92..95
FT                   /evidence="ECO:0007829|PDB:2B19"
FT   HELIX           98..101
FT                   /evidence="ECO:0007829|PDB:2B19"
FT   HELIX           102..106
FT                   /evidence="ECO:0007829|PDB:2B19"
SQ   SEQUENCE   129 AA;  15003 MW;  51412C1692368DE4 CRC64;
     MKILVALAVF FLVSTQLFAE EIGANDDLNY WSDWYDSDQI KEELPEPFEH LLQRIARRPK
     PQQFFGLMGK RDADSSIEKQ VALLKALYGH GQISHKRHKT DSFVGLMGKR ALNSVAYERS
     AMQNYERRR
//