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Protein

Tachykinin-3

Gene

TAC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles (By similarity). Is a critical central regulator of gonadal function.By similarity1 Publication

GO - Molecular functioni

  • receptor binding Source: ProtInc

GO - Biological processi

  • female pregnancy Source: ProtInc
  • neuropeptide signaling pathway Source: UniProtKB-KW
  • tachykinin receptor signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Neuropeptide

Enzyme and pathway databases

ReactomeiR-HSA-380095. Tachykinin receptors bind tachykinins.
R-HSA-416476. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Tachykinin-3
Alternative name(s):
ZNEUROK1
Cleaved into the following chain:
Neurokinin-B
Short name:
NKB
Alternative name(s):
Neuromedin-K
Gene namesi
Name:TAC3
Synonyms:NKNB
ORF Names:UNQ585/PRO1155
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11521. TAC3.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 10 with or without anosmia (HH10)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:614839
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801R → S in HH10; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; the patient also carries a mutation in HS6ST1. 1 Publication
Corresponds to variant rs727505372 [ dbSNP | Ensembl ].
VAR_069969
Natural varianti90 – 901M → T in HH10; has markedly reduced activity. 1 Publication
Corresponds to variant rs121918123 [ dbSNP | Ensembl ].
VAR_069176

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

MalaCardsiTAC3.
MIMi614839. phenotype.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA36298.

Polymorphism and mutation databases

BioMutaiTAC3.
DMDMi18203501.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Sequence analysisAdd
BLAST
Propeptidei17 – 7862By similarityPRO_0000033565Add
BLAST
Peptidei81 – 9010Neurokinin-BPRO_0000033566
Propeptidei94 – 12128By similarityPRO_0000033567Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei90 – 901Methionine amideBy similarity

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Proteomic databases

EPDiQ9UHF0.
PaxDbiQ9UHF0.
PeptideAtlasiQ9UHF0.
PRIDEiQ9UHF0.

PTM databases

iPTMnetiQ9UHF0.

Miscellaneous databases

PMAP-CutDBQ9UHF0.

Expressioni

Developmental stagei

In pregnancy, the expression of NKB is confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB can be detected in plasma as early as week 9, and plasma concentrations of NKB are grossly elevated in pregnancy-induced hypertension and pre-eclampsia.

Gene expression databases

BgeeiQ9UHF0.
CleanExiHS_TAC3.
ExpressionAtlasiQ9UHF0. baseline and differential.
GenevisibleiQ9UHF0. HS.

Organism-specific databases

HPAiHPA045919.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TACR3P293712EBI-6655626,EBI-6655576

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi112729. 8 interactions.
IntActiQ9UHF0. 7 interactions.
MINTiMINT-1381829.
STRINGi9606.ENSP00000300108.

Chemistry

BindingDBiQ9UHF0.

Structurei

Secondary structure

1
121
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi82 – 898Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P9FNMR-A81-90[»]
ProteinModelPortaliQ9UHF0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UHF0.

Family & Domainsi

Sequence similaritiesi

Belongs to the tachykinin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J2QH. Eukaryota.
ENOG4111D7S. LUCA.
GeneTreeiENSGT00390000000335.
HOGENOMiHOG000154597.
HOVERGENiHBG016587.
InParanoidiQ9UHF0.
KOiK05240.
OMAiKASVGPK.
OrthoDBiEOG7G1V86.
PhylomeDBiQ9UHF0.
TreeFamiTF337038.

Family and domain databases

InterProiIPR003635. Neurokinin-B/TAC3.
IPR013055. Tachy_Neuro_lke_CS.
[Graphical view]
PANTHERiPTHR15536. PTHR15536. 1 hit.
PfamiPF03823. Neurokinin_B. 1 hit.
[Graphical view]
PIRSFiPIRSF001843. Neurokinin. 1 hit.
PRINTSiPR01828. NEUROKININB.
PROSITEiPS00267. TACHYKININ. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHF0-1) [UniParc]FASTAAdd to basket

Also known as: Beta tachykinin 3

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRIMLLFTAI LAFSLAQSFG AVCKEPQEEV VPGGGRSKRD PDLYQLLQRL
60 70 80 90 100
FKSHSSLEGL LKALSQASTD PKESTSPEKR DMHDFFVGLM GKRSVQPDSP
110 120
TDVNQENVPS FGILKYPPRA E
Length:121
Mass (Da):13,438
Last modified:May 1, 2000 - v1
Checksum:i14C9AFE2EE9EDECA
GO
Isoform 2 (identifier: Q9UHF0-2) [UniParc]FASTAAdd to basket

Also known as: Alpha tachykinin 3

The sequence of this isoform differs from the canonical sequence as follows:
     98-121: DSPTDVNQENVPSFGILKYPPRAE → EGKTGPFLPSVRVPRPLHPNQLGSTGKSSLGTEEQRPL

Show »
Length:135
Mass (Da):14,833
Checksum:i4C6DBBDBE30851F3
GO
Isoform 3 (identifier: Q9UHF0-3) [UniParc]FASTAAdd to basket

Also known as: Gamma tachykinin 3

The sequence of this isoform differs from the canonical sequence as follows:
     80-98: RDMHDFFVGLMGKRSVQPD → H

Show »
Length:103
Mass (Da):11,358
Checksum:i2D0026B586B03FC6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti121 – 1211E → D in CAG33474 (Ref. 5) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801R → S in HH10; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; the patient also carries a mutation in HS6ST1. 1 Publication
Corresponds to variant rs727505372 [ dbSNP | Ensembl ].
VAR_069969
Natural varianti90 – 901M → T in HH10; has markedly reduced activity. 1 Publication
Corresponds to variant rs121918123 [ dbSNP | Ensembl ].
VAR_069176

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei80 – 9819RDMHD…SVQPD → H in isoform 3. 1 PublicationVSP_013186Add
BLAST
Alternative sequencei98 – 12124DSPTD…PPRAE → EGKTGPFLPSVRVPRPLHPN QLGSTGKSSLGTEEQRPL in isoform 2. 2 PublicationsVSP_013187Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF186112 mRNA. Translation: AAF01430.1.
AF216586 mRNA. Translation: AAF76980.1.
AF537113 mRNA. Translation: AAQ10783.1.
AF537114 mRNA. Translation: AAQ10784.1.
AF537115 mRNA. Translation: AAQ10785.1.
AF537116 mRNA. Translation: AAQ10786.1.
AF537117 mRNA. Translation: AAQ10787.1.
AF537118 mRNA. Translation: AAQ10788.1.
AF537119 mRNA. Translation: AAQ10789.1.
AF537120 mRNA. Translation: AAQ10790.1.
AF537121 mRNA. Translation: AAQ10791.1.
AY358679 mRNA. Translation: AAQ89042.1.
CR457193 mRNA. Translation: CAG33474.1.
BC032145 mRNA. Translation: AAH32145.1.
CCDSiCCDS53803.1. [Q9UHF0-3]
CCDS8928.1. [Q9UHF0-1]
RefSeqiNP_001171525.1. NM_001178054.1. [Q9UHF0-3]
NP_037383.1. NM_013251.3. [Q9UHF0-1]
UniGeneiHs.9730.

Genome annotation databases

EnsembliENST00000300108; ENSP00000300108; ENSG00000166863. [Q9UHF0-1]
ENST00000357616; ENSP00000350236; ENSG00000166863. [Q9UHF0-2]
ENST00000379411; ENSP00000368721; ENSG00000166863. [Q9UHF0-3]
ENST00000393867; ENSP00000377445; ENSG00000166863. [Q9UHF0-2]
ENST00000415231; ENSP00000402995; ENSG00000166863. [Q9UHF0-1]
ENST00000423597; ENSP00000416292; ENSG00000166863. [Q9UHF0-3]
ENST00000438756; ENSP00000408131; ENSG00000166863. [Q9UHF0-2]
ENST00000441881; ENSP00000408208; ENSG00000166863. [Q9UHF0-3]
ENST00000458521; ENSP00000404056; ENSG00000166863. [Q9UHF0-1]
ENST00000615887; ENSP00000483110; ENSG00000166863. [Q9UHF0-1]
GeneIDi6866.
KEGGihsa:6866.
UCSCiuc001smo.4. human. [Q9UHF0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF186112 mRNA. Translation: AAF01430.1.
AF216586 mRNA. Translation: AAF76980.1.
AF537113 mRNA. Translation: AAQ10783.1.
AF537114 mRNA. Translation: AAQ10784.1.
AF537115 mRNA. Translation: AAQ10785.1.
AF537116 mRNA. Translation: AAQ10786.1.
AF537117 mRNA. Translation: AAQ10787.1.
AF537118 mRNA. Translation: AAQ10788.1.
AF537119 mRNA. Translation: AAQ10789.1.
AF537120 mRNA. Translation: AAQ10790.1.
AF537121 mRNA. Translation: AAQ10791.1.
AY358679 mRNA. Translation: AAQ89042.1.
CR457193 mRNA. Translation: CAG33474.1.
BC032145 mRNA. Translation: AAH32145.1.
CCDSiCCDS53803.1. [Q9UHF0-3]
CCDS8928.1. [Q9UHF0-1]
RefSeqiNP_001171525.1. NM_001178054.1. [Q9UHF0-3]
NP_037383.1. NM_013251.3. [Q9UHF0-1]
UniGeneiHs.9730.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P9FNMR-A81-90[»]
ProteinModelPortaliQ9UHF0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112729. 8 interactions.
IntActiQ9UHF0. 7 interactions.
MINTiMINT-1381829.
STRINGi9606.ENSP00000300108.

Chemistry

BindingDBiQ9UHF0.

PTM databases

iPTMnetiQ9UHF0.

Polymorphism and mutation databases

BioMutaiTAC3.
DMDMi18203501.

Proteomic databases

EPDiQ9UHF0.
PaxDbiQ9UHF0.
PeptideAtlasiQ9UHF0.
PRIDEiQ9UHF0.

Protocols and materials databases

DNASUi6866.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300108; ENSP00000300108; ENSG00000166863. [Q9UHF0-1]
ENST00000357616; ENSP00000350236; ENSG00000166863. [Q9UHF0-2]
ENST00000379411; ENSP00000368721; ENSG00000166863. [Q9UHF0-3]
ENST00000393867; ENSP00000377445; ENSG00000166863. [Q9UHF0-2]
ENST00000415231; ENSP00000402995; ENSG00000166863. [Q9UHF0-1]
ENST00000423597; ENSP00000416292; ENSG00000166863. [Q9UHF0-3]
ENST00000438756; ENSP00000408131; ENSG00000166863. [Q9UHF0-2]
ENST00000441881; ENSP00000408208; ENSG00000166863. [Q9UHF0-3]
ENST00000458521; ENSP00000404056; ENSG00000166863. [Q9UHF0-1]
ENST00000615887; ENSP00000483110; ENSG00000166863. [Q9UHF0-1]
GeneIDi6866.
KEGGihsa:6866.
UCSCiuc001smo.4. human. [Q9UHF0-1]

Organism-specific databases

CTDi6866.
GeneCardsiTAC3.
H-InvDBHIX0010742.
HGNCiHGNC:11521. TAC3.
HPAiHPA045919.
MalaCardsiTAC3.
MIMi162330. gene.
614839. phenotype.
neXtProtiNX_Q9UHF0.
Orphaneti432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA36298.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J2QH. Eukaryota.
ENOG4111D7S. LUCA.
GeneTreeiENSGT00390000000335.
HOGENOMiHOG000154597.
HOVERGENiHBG016587.
InParanoidiQ9UHF0.
KOiK05240.
OMAiKASVGPK.
OrthoDBiEOG7G1V86.
PhylomeDBiQ9UHF0.
TreeFamiTF337038.

Enzyme and pathway databases

ReactomeiR-HSA-380095. Tachykinin receptors bind tachykinins.
R-HSA-416476. G alpha (q) signalling events.

Miscellaneous databases

EvolutionaryTraceiQ9UHF0.
GeneWikiiTAC3.
GenomeRNAii6866.
PMAP-CutDBQ9UHF0.
PROiQ9UHF0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UHF0.
CleanExiHS_TAC3.
ExpressionAtlasiQ9UHF0. baseline and differential.
GenevisibleiQ9UHF0. HS.

Family and domain databases

InterProiIPR003635. Neurokinin-B/TAC3.
IPR013055. Tachy_Neuro_lke_CS.
[Graphical view]
PANTHERiPTHR15536. PTHR15536. 1 hit.
PfamiPF03823. Neurokinin_B. 1 hit.
[Graphical view]
PIRSFiPIRSF001843. Neurokinin. 1 hit.
PRINTSiPR01828. NEUROKININB.
PROSITEiPS00267. TACHYKININ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Sheppard P., Jelinek L., Whitmore T., Blumberg H., Lehner J., O'Hara P.
    Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia."
    Page N.M., Woods R.J., Gardiner S.M., Lomthiasong K., Gladwell R.T., Butlin D.J., Manyonda I.T., Lowry P.J.
    Nature 405:797-800(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Placenta.
  3. "The peripheral expression of neurokinin B, its splice variants and its receptors."
    Bell N.J., Page N.M.
    Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  5. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  7. "TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction."
    Topaloglu A.K., Reimann F., Guclu M., Yalin A.S., Kotan L.D., Porter K.M., Serin A., Mungan N.O., Cook J.R., Ozbek M.N., Imamoglu S., Akalin N.S., Yuksel B., O'Rahilly S., Semple R.K.
    Nat. Genet. 41:354-358(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN REGULATION OF GONADAL FUNCTION, VARIANT HH10 THR-90, CHARACTERIZATION OF VARIANT HH10 THR-90.
  8. Cited for: VARIANT HH10 SER-80.

Entry informationi

Entry nameiTKNK_HUMAN
AccessioniPrimary (citable) accession number: Q9UHF0
Secondary accession number(s): Q6IAG2, Q71BC6, Q71BC9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: July 6, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.