TKN4_HUMAN
ID TKN4_HUMAN Reviewed; 113 AA.
AC Q86UU9; Q2M2P1; Q6ECK8; Q86UU6; Q86UU7; Q86UU8; Q8IWZ7;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Tachykinin-4;
DE AltName: Full=Preprotachykinin-C;
DE Short=PPT-C;
DE Contains:
DE RecName: Full=Endokinin-A;
DE Short=EKA;
DE Contains:
DE RecName: Full=Endokinin-A/B;
DE Short=EKA/B;
DE Contains:
DE RecName: Full=Endokinin-C;
DE Short=EKC;
DE Flags: Precursor;
GN Name=TAC4 {ECO:0000312|HGNC:HGNC:16641};
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] {ECO:0000305, ECO:0000312|EMBL:AAP30874.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, TISSUE
RP SPECIFICITY, AND AMIDATION AT MET-67 AND LEU-95.
RX PubMed=12716968; DOI=10.1073/pnas.0931458100;
RA Page N.M., Bell N.J., Gardiner S.M., Manyonda I.T., Brayley K.J.,
RA Strange P.G., Lowry P.J.;
RT "Characterization of the endokinins: human tachykinins with cardiovascular
RT activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6245-6250(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAS46596.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Page N.M.;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAS46596.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAN77128.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-72 (ISOFORM 1).
RX PubMed=12383518; DOI=10.1016/s0378-1119(02)00861-2;
RA Kurtz M.M., Wang R., Clements M.K., Cascieri M.A., Austin C.P.,
RA Cunningham B.R., Chicchi G.G., Liu Q.;
RT "Identification, localization and receptor characterization of novel
RT mammalian substance P-like peptides.";
RL Gene 296:205-212(2002).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAI00841.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-72 (ISOFORMS 2/3/4/5).
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 [6] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=12788812; DOI=10.1038/sj.bjp.0705279;
RA Patak E., Candenas M.L., Pennefather J.N., Ziccone S., Lilley A.,
RA Martin J.D., Flores C., Mantecon A.G., Story M.E., Pinto F.M.;
RT "Tachykinins and tachykinin receptors in human uterus.";
RL Br. J. Pharmacol. 139:523-532(2003).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=17101218; DOI=10.1016/j.neulet.2006.09.024;
RA Yoshioka D., Takebuchi F., Nishimori T., Naono R., Ikeda T., Nakayama T.;
RT "Intrathecal administration of the common carboxyl-terminal decapeptide in
RT endokinin A and endokinin B evokes scratching behavior and thermal
RT hyperalgesia in the rat.";
RL Neurosci. Lett. 410:193-197(2006).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=17655832; DOI=10.1016/j.brainres.2007.05.062;
RA Naono R., Nakayama T., Ikeda T., Matsushima O., Nishimori T.;
RT "Leucine at the carboxyl-terminal of endokinins C and D contributes to
RT elicitation of the antagonistic effect on substance P in rat pain
RT processing.";
RL Brain Res. 1165:71-80(2007).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=17437961; DOI=10.1093/humrep/dem069;
RA Ravina C.G., Seda M., Pinto F.M., Orea A., Fernandez-Sanchez M.,
RA Pintado C.O., Candenas M.L.;
RT "A role for tachykinins in the regulation of human sperm motility.";
RL Hum. Reprod. 22:1617-1625(2007).
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. Endokinin-A
CC induces thermal hyperalgesia and pain-related behavior such as
CC scratching following intrathecal administration in rats. These effects
CC are suppressed by treatment with endokinin-C. Endokinin-A/B reduces
CC arterial blood pressure and increases sperm motility.
CC {ECO:0000269|PubMed:12716968, ECO:0000269|PubMed:17101218,
CC ECO:0000269|PubMed:17437961, ECO:0000269|PubMed:17655832}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1 {ECO:0000269|PubMed:12716968}; Synonyms=Alpha
CC {ECO:0000269|PubMed:12716968};
CC IsoId=Q86UU9-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:12716968}; Synonyms=Beta
CC {ECO:0000269|PubMed:12716968};
CC IsoId=Q86UU9-2; Sequence=VSP_052676, VSP_052677;
CC Name=3 {ECO:0000269|PubMed:12716968}; Synonyms=Gamma
CC {ECO:0000269|PubMed:12716968};
CC IsoId=Q86UU9-3; Sequence=VSP_052676, VSP_052681;
CC Name=4 {ECO:0000269|PubMed:12716968}; Synonyms=Delta
CC {ECO:0000269|PubMed:12716968};
CC IsoId=Q86UU9-4; Sequence=VSP_052676, VSP_052680;
CC Name=5;
CC IsoId=Q86UU9-5; Sequence=VSP_052676;
CC -!- TISSUE SPECIFICITY: Expressed at low levels in the uterus of both
CC pregnant and non-pregnant women. Isoform 1 is found only in the adrenal
CC gland and fetal liver. Isoform 2 is found in heart, liver, bone marrow,
CC prostate, adrenal gland and testis. Isoform 3 and isoform 4 are
CC expressed predominantly in adrenal gland and placenta.
CC {ECO:0000269|PubMed:12716968, ECO:0000269|PubMed:12788812}.
CC -!- SIMILARITY: Belongs to the tachykinin family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI00841.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAI00843.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAI00844.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAN77128.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=EAW94657.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF515828; AAP30874.1; -; mRNA.
DR EMBL; AF515829; AAP30875.1; -; mRNA.
DR EMBL; AF515830; AAP30876.1; -; mRNA.
DR EMBL; AF515831; AAP30877.1; -; mRNA.
DR EMBL; AY471574; AAS46596.1; -; mRNA.
DR EMBL; CH471109; EAW94657.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF521560; AAN77128.1; ALT_SEQ; mRNA.
DR EMBL; BC100840; AAI00841.1; ALT_SEQ; mRNA.
DR EMBL; BC100842; AAI00843.1; ALT_SEQ; mRNA.
DR EMBL; BC100843; AAI00844.1; ALT_SEQ; mRNA.
DR CCDS; CCDS42357.1; -. [Q86UU9-1]
DR CCDS; CCDS42358.1; -. [Q86UU9-4]
DR CCDS; CCDS42359.1; -. [Q86UU9-2]
DR CCDS; CCDS42360.1; -. [Q86UU9-3]
DR CCDS; CCDS45727.1; -. [Q86UU9-5]
DR RefSeq; NP_001070971.1; NM_001077503.1. [Q86UU9-2]
DR RefSeq; NP_001070972.1; NM_001077504.1. [Q86UU9-3]
DR RefSeq; NP_001070973.1; NM_001077505.1. [Q86UU9-4]
DR RefSeq; NP_001070974.1; NM_001077506.1. [Q86UU9-5]
DR RefSeq; NP_733786.2; NM_170685.2. [Q86UU9-1]
DR PDB; 2MOC; NMR; -; A=57-67.
DR PDBsum; 2MOC; -.
DR AlphaFoldDB; Q86UU9; -.
DR SMR; Q86UU9; -.
DR BioGRID; 129073; 4.
DR STRING; 9606.ENSP00000334042; -.
DR BioMuta; TAC4; -.
DR DMDM; 74723510; -.
DR MassIVE; Q86UU9; -.
DR PaxDb; Q86UU9; -.
DR PRIDE; Q86UU9; -.
DR ProteomicsDB; 69900; -. [Q86UU9-1]
DR ProteomicsDB; 69902; -. [Q86UU9-3]
DR ProteomicsDB; 69904; -. [Q86UU9-5]
DR Antibodypedia; 68331; 66 antibodies from 12 providers.
DR DNASU; 255061; -.
DR Ensembl; ENST00000326219.5; ENSP00000325286.5; ENSG00000176358.16. [Q86UU9-3]
DR Ensembl; ENST00000334568.8; ENSP00000334042.4; ENSG00000176358.16. [Q86UU9-1]
DR Ensembl; ENST00000352793.6; ENSP00000340461.2; ENSG00000176358.16. [Q86UU9-4]
DR Ensembl; ENST00000398154.5; ENSP00000381221.1; ENSG00000176358.16. [Q86UU9-2]
DR Ensembl; ENST00000436235.6; ENSP00000399702.1; ENSG00000176358.16. [Q86UU9-5]
DR GeneID; 255061; -.
DR KEGG; hsa:255061; -.
DR MANE-Select; ENST00000436235.6; ENSP00000399702.1; NM_001077506.2; NP_001070974.1. [Q86UU9-5]
DR UCSC; uc002ipo.1; human. [Q86UU9-1]
DR CTD; 255061; -.
DR DisGeNET; 255061; -.
DR GeneCards; TAC4; -.
DR HGNC; HGNC:16641; TAC4.
DR HPA; ENSG00000176358; Tissue enhanced (pituitary).
DR MIM; 607833; gene.
DR neXtProt; NX_Q86UU9; -.
DR OpenTargets; ENSG00000176358; -.
DR PharmGKB; PA134944925; -.
DR VEuPathDB; HostDB:ENSG00000176358; -.
DR eggNOG; ENOG502TEEE; Eukaryota.
DR GeneTree; ENSGT00390000015220; -.
DR HOGENOM; CLU_2677305_0_0_1; -.
DR InParanoid; Q86UU9; -.
DR OMA; LMELFVC; -.
DR OrthoDB; 1512743at2759; -.
DR PhylomeDB; Q86UU9; -.
DR TreeFam; TF338519; -.
DR PathwayCommons; Q86UU9; -.
DR SignaLink; Q86UU9; -.
DR BioGRID-ORCS; 255061; 23 hits in 1057 CRISPR screens.
DR GeneWiki; TAC4; -.
DR GenomeRNAi; 255061; -.
DR Pharos; Q86UU9; Tbio.
DR PRO; PR:Q86UU9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q86UU9; protein.
DR Bgee; ENSG00000176358; Expressed in tendon of biceps brachii and 122 other tissues.
DR ExpressionAtlas; Q86UU9; baseline and differential.
DR Genevisible; Q86UU9; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB.
DR GO; GO:0031837; F:substance K receptor binding; IPI:UniProtKB.
DR GO; GO:0031835; F:substance P receptor binding; IPI:UniProtKB.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:1904057; P:negative regulation of sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IDA:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:1902093; P:positive regulation of flagellated sperm motility; IDA:UniProtKB.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IEA:UniProtKB-KW.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; IDA:UniProtKB.
DR InterPro; IPR013055; Tachy_Neuro_lke_CS.
DR PROSITE; PS00267; TACHYKININ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amidation;
KW Cleavage on pair of basic residues; Hypotensive agent; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PEPTIDE 21..67
FT /note="Endokinin-A"
FT /id="PRO_5000063346"
FT PEPTIDE 58..67
FT /note="Endokinin-A/B"
FT /id="PRO_0000320011"
FT PROPEP 71..79
FT /evidence="ECO:0000250"
FT /id="PRO_0000320012"
FT PEPTIDE 82..95
FT /note="Endokinin-C"
FT /id="PRO_5000063347"
FT PROPEP 98..113
FT /evidence="ECO:0000250"
FT /id="PRO_0000320013"
FT MOD_RES 67
FT /note="Methionine amide"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:12716968"
FT MOD_RES 95
FT /note="Leucine amide"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:12716968"
FT VAR_SEQ 36..41
FT /note="Missing (in isoform 2, isoform 3, isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:12716968, ECO:0000303|Ref.2"
FT /id="VSP_052676"
FT VAR_SEQ 73..83
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12716968"
FT /id="VSP_052677"
FT VAR_SEQ 75..105
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12716968"
FT /id="VSP_052680"
FT VAR_SEQ 84..103
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12716968"
FT /id="VSP_052681"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:2MOC"
FT HELIX 62..66
FT /evidence="ECO:0007829|PDB:2MOC"
SQ SEQUENCE 113 AA; 12305 MW; B8772582351C9163 CRC64;
MLPCLALLLL MELSVCTVAG DGGEEQTLST EAETWVIVAL EEGAGPSIQL QLQEVKTGKA
SQFFGLMGKR VGGRPLIQPR RKKAYQLEHT FQGLLGKRSL FTEGREDEAQ GSE
