TKNK_HUMAN
ID TKNK_HUMAN Reviewed; 121 AA.
AC Q9UHF0; Q6IAG2; Q71BC6; Q71BC9;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Tachykinin-3;
DE AltName: Full=ZNEUROK1;
DE Contains:
DE RecName: Full=Neurokinin-B;
DE Short=NKB;
DE AltName: Full=Neuromedin-K;
DE Flags: Precursor;
GN Name=TAC3; Synonyms=NKNB; ORFNames=UNQ585/PRO1155;
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 1).
RA Sheppard P., Jelinek L., Whitmore T., Blumberg H., Lehner J., O'Hara P.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=10866201; DOI=10.1038/35015579;
RA Page N.M., Woods R.J., Gardiner S.M., Lomthiasong K., Gladwell R.T.,
RA Butlin D.J., Manyonda I.T., Lowry P.J.;
RT "Excessive placental secretion of neurokinin B during the third trimester
RT causes pre-eclampsia.";
RL Nature 405:797-800(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RA Bell N.J., Page N.M.;
RT "The peripheral expression of neurokinin B, its splice variants and its
RT receptors.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
RP ROLE IN REGULATION OF GONADAL FUNCTION, VARIANT HH10 THR-90, AND
RP CHARACTERIZATION OF VARIANT HH10 THR-90.
RX PubMed=19079066; DOI=10.1038/ng.306;
RA Topaloglu A.K., Reimann F., Guclu M., Yalin A.S., Kotan L.D., Porter K.M.,
RA Serin A., Mungan N.O., Cook J.R., Ozbek M.N., Imamoglu S., Akalin N.S.,
RA Yuksel B., O'Rahilly S., Semple R.K.;
RT "TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal
RT a key role for Neurokinin B in the central control of reproduction.";
RL Nat. Genet. 41:354-358(2009).
RN [8]
RP VARIANT HH10 SER-80.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
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 (By similarity).
CC Is a critical central regulator of gonadal function. {ECO:0000250,
CC ECO:0000269|PubMed:19079066}.
CC -!- INTERACTION:
CC Q9UHF0; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-717325, EBI-1055254;
CC Q9UHF0; A5D903: PRB1; NbExp=3; IntAct=EBI-717325, EBI-10173935;
CC Q9UHF0; A0A087WZY1; NbExp=3; IntAct=EBI-717325, EBI-13387614;
CC PRO_0000033566; P29371: TACR3; NbExp=2; IntAct=EBI-6655626, EBI-6655576;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Beta tachykinin 3;
CC IsoId=Q9UHF0-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha tachykinin 3;
CC IsoId=Q9UHF0-2; Sequence=VSP_013187;
CC Name=3; Synonyms=Gamma tachykinin 3;
CC IsoId=Q9UHF0-3; Sequence=VSP_013186;
CC -!- DEVELOPMENTAL STAGE: In pregnancy, the expression of NKB is confined to
CC the outer syncytiotrophoblast of the placenta, significant
CC concentrations of NKB can be detected in plasma as early as week 9, and
CC plasma concentrations of NKB are grossly elevated in pregnancy-induced
CC hypertension and pre-eclampsia.
CC -!- DISEASE: Hypogonadotropic hypogonadism 10 with or without anosmia
CC (HH10) [MIM:614839]: A disorder characterized by absent or incomplete
CC sexual maturation by the age of 18 years, in conjunction with low
CC levels of circulating gonadotropins and testosterone and no other
CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is
CC associated with non-reproductive phenotypes, such as anosmia, cleft
CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related
CC to the absence or hypoplasia of the olfactory bulbs and tracts.
CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and
CC probably results from a failure of embryonic migration of gonadotropin-
CC releasing hormone-synthesizing neurons. In the presence of anosmia,
CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann
CC syndrome, whereas in the presence of a normal sense of smell, it has
CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:19079066, ECO:0000269|PubMed:23643382}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the tachykinin family. {ECO:0000305}.
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DR EMBL; AF186112; AAF01430.1; -; mRNA.
DR EMBL; AF216586; AAF76980.1; -; mRNA.
DR EMBL; AF537113; AAQ10783.1; -; mRNA.
DR EMBL; AF537114; AAQ10784.1; -; mRNA.
DR EMBL; AF537115; AAQ10785.1; -; mRNA.
DR EMBL; AF537116; AAQ10786.1; -; mRNA.
DR EMBL; AF537117; AAQ10787.1; -; mRNA.
DR EMBL; AF537118; AAQ10788.1; -; mRNA.
DR EMBL; AF537119; AAQ10789.1; -; mRNA.
DR EMBL; AF537120; AAQ10790.1; -; mRNA.
DR EMBL; AF537121; AAQ10791.1; -; mRNA.
DR EMBL; AY358679; AAQ89042.1; -; mRNA.
DR EMBL; CR457193; CAG33474.1; -; mRNA.
DR EMBL; BC032145; AAH32145.1; -; mRNA.
DR CCDS; CCDS53803.1; -. [Q9UHF0-3]
DR CCDS; CCDS8928.1; -. [Q9UHF0-1]
DR RefSeq; NP_001171525.1; NM_001178054.1. [Q9UHF0-3]
DR RefSeq; NP_037383.1; NM_013251.3. [Q9UHF0-1]
DR PDB; 1P9F; NMR; -; A=81-90.
DR PDBsum; 1P9F; -.
DR AlphaFoldDB; Q9UHF0; -.
DR SMR; Q9UHF0; -.
DR BioGRID; 112729; 16.
DR IntAct; Q9UHF0; 10.
DR STRING; 9606.ENSP00000483110; -.
DR BindingDB; Q9UHF0; -.
DR ChEMBL; CHEMBL3707470; -.
DR DrugBank; DB09130; Copper.
DR iPTMnet; Q9UHF0; -.
DR PhosphoSitePlus; Q9UHF0; -.
DR BioMuta; TAC3; -.
DR DMDM; 18203501; -.
DR MassIVE; Q9UHF0; -.
DR PaxDb; Q9UHF0; -.
DR PeptideAtlas; Q9UHF0; -.
DR PRIDE; Q9UHF0; -.
DR ProteomicsDB; 84336; -. [Q9UHF0-1]
DR ProteomicsDB; 84337; -. [Q9UHF0-2]
DR ProteomicsDB; 84338; -. [Q9UHF0-3]
DR Antibodypedia; 28422; 267 antibodies from 28 providers.
DR DNASU; 6866; -.
DR Ensembl; ENST00000300108.7; ENSP00000300108.3; ENSG00000166863.13. [Q9UHF0-1]
DR Ensembl; ENST00000357616.7; ENSP00000350236.3; ENSG00000166863.13. [Q9UHF0-2]
DR Ensembl; ENST00000379411.6; ENSP00000368721.2; ENSG00000166863.13. [Q9UHF0-3]
DR Ensembl; ENST00000393867.5; ENSP00000377445.1; ENSG00000166863.13. [Q9UHF0-2]
DR Ensembl; ENST00000415231.1; ENSP00000402995.1; ENSG00000166863.13. [Q9UHF0-1]
DR Ensembl; ENST00000423597.5; ENSP00000416292.1; ENSG00000166863.13. [Q9UHF0-3]
DR Ensembl; ENST00000438756.5; ENSP00000408131.1; ENSG00000166863.13. [Q9UHF0-2]
DR Ensembl; ENST00000441881.5; ENSP00000408208.1; ENSG00000166863.13. [Q9UHF0-3]
DR Ensembl; ENST00000458521.7; ENSP00000404056.2; ENSG00000166863.13. [Q9UHF0-1]
DR GeneID; 6866; -.
DR KEGG; hsa:6866; -.
DR MANE-Select; ENST00000458521.7; ENSP00000404056.2; NM_013251.4; NP_037383.1.
DR UCSC; uc001smo.4; human. [Q9UHF0-1]
DR CTD; 6866; -.
DR DisGeNET; 6866; -.
DR GeneCards; TAC3; -.
DR GeneReviews; TAC3; -.
DR HGNC; HGNC:11521; TAC3.
DR HPA; ENSG00000166863; Tissue enriched (placenta).
DR MalaCards; TAC3; -.
DR MIM; 162330; gene.
DR MIM; 614839; phenotype.
DR neXtProt; NX_Q9UHF0; -.
DR OpenTargets; ENSG00000166863; -.
DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
DR PharmGKB; PA36298; -.
DR VEuPathDB; HostDB:ENSG00000166863; -.
DR eggNOG; ENOG502S4B9; Eukaryota.
DR GeneTree; ENSGT00390000000335; -.
DR HOGENOM; CLU_138627_1_0_1; -.
DR InParanoid; Q9UHF0; -.
DR OMA; GGHNKKD; -.
DR PhylomeDB; Q9UHF0; -.
DR TreeFam; TF337038; -.
DR PathwayCommons; Q9UHF0; -.
DR Reactome; R-HSA-380095; Tachykinin receptors bind tachykinins.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; Q9UHF0; -.
DR BioGRID-ORCS; 6866; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; TAC3; human.
DR EvolutionaryTrace; Q9UHF0; -.
DR GeneWiki; TAC3; -.
DR GenomeRNAi; 6866; -.
DR Pharos; Q9UHF0; Tchem.
DR PRO; PR:Q9UHF0; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9UHF0; protein.
DR Bgee; ENSG00000166863; Expressed in decidua and 136 other tissues.
DR ExpressionAtlas; Q9UHF0; baseline and differential.
DR Genevisible; Q9UHF0; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0031836; F:neuromedin K receptor binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0031837; F:substance K receptor binding; IPI:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0045777; P:positive regulation of blood pressure; IBA:GO_Central.
DR GO; GO:1902093; P:positive regulation of flagellated sperm motility; IDA:UniProtKB.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; TAS:ProtInc.
DR InterPro; IPR003635; Neurokinin-B/TAC3.
DR InterPro; IPR013055; Tachy_Neuro_lke_CS.
DR PANTHER; PTHR15536; PTHR15536; 1.
DR Pfam; PF03823; Neurokinin_B; 1.
DR PIRSF; PIRSF001843; Neurokinin; 1.
DR PRINTS; PR01828; NEUROKININB.
DR PROSITE; PS00267; TACHYKININ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amidation;
KW Cleavage on pair of basic residues; Disease variant;
KW Hypogonadotropic hypogonadism; Neuropeptide; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..78
FT /evidence="ECO:0000250"
FT /id="PRO_0000033565"
FT PEPTIDE 81..90
FT /note="Neurokinin-B"
FT /id="PRO_0000033566"
FT PROPEP 94..121
FT /evidence="ECO:0000250"
FT /id="PRO_0000033567"
FT REGION 93..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 90
FT /note="Methionine amide"
FT /evidence="ECO:0000250"
FT VAR_SEQ 80..98
FT /note="RDMHDFFVGLMGKRSVQPD -> H (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_013186"
FT VAR_SEQ 98..121
FT /note="DSPTDVNQENVPSFGILKYPPRAE -> EGKTGPFLPSVRVPRPLHPNQLGS
FT TGKSSLGTEEQRPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309, ECO:0000303|Ref.3"
FT /id="VSP_013187"
FT VARIANT 80
FT /note="R -> S (in HH10; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism; the patient also
FT carries a mutation in HS6ST1; dbSNP:rs727505372)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069969"
FT VARIANT 90
FT /note="M -> T (in HH10; has markedly reduced activity;
FT dbSNP:rs121918123)"
FT /evidence="ECO:0000269|PubMed:19079066"
FT /id="VAR_069176"
FT CONFLICT 121
FT /note="E -> D (in Ref. 5; CAG33474)"
FT /evidence="ECO:0000305"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:1P9F"
SQ SEQUENCE 121 AA; 13438 MW; 14C9AFE2EE9EDECA CRC64;
MRIMLLFTAI LAFSLAQSFG AVCKEPQEEV VPGGGRSKRD PDLYQLLQRL FKSHSSLEGL
LKALSQASTD PKESTSPEKR DMHDFFVGLM GKRSVQPDSP TDVNQENVPS FGILKYPPRA
E
