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Protein

Neuromedin-K receptor

Gene

TACR3

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

Functioni

This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.

GO - Molecular functioni

  • tachykinin receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169836-MONOMER.
ReactomeiR-HSA-380095. Tachykinin receptors bind tachykinins.
R-HSA-416476. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuromedin-K receptor
Short name:
NKR
Alternative name(s):
NK-3 receptor
Short name:
NK-3R
Neurokinin B receptor
Tachykinin receptor 3
Gene namesi
Name:TACR3
Synonyms:NK3R, TAC3R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:11528. TACR3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 84ExtracellularSequence analysisAdd BLAST84
Transmembranei85 – 107Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini108 – 117CytoplasmicSequence analysis10
Transmembranei118 – 139Helical; Name=2Sequence analysisAdd BLAST22
Topological domaini140 – 159ExtracellularSequence analysisAdd BLAST20
Transmembranei160 – 181Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini182 – 201CytoplasmicSequence analysisAdd BLAST20
Transmembranei202 – 222Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini223 – 245ExtracellularSequence analysisAdd BLAST23
Transmembranei246 – 270Helical; Name=5Sequence analysisAdd BLAST25
Topological domaini271 – 299CytoplasmicSequence analysisAdd BLAST29
Transmembranei300 – 321Helical; Name=6Sequence analysisAdd BLAST22
Topological domaini322 – 334ExtracellularSequence analysisAdd BLAST13
Transmembranei335 – 359Helical; Name=7Sequence analysisAdd BLAST25
Topological domaini360 – 465CytoplasmicSequence analysisAdd BLAST106

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 11 with or without anosmia (HH11)3 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in TACR3 as well as in other HH-associated genes including FGFR1, SPRY4 and KAL1 (PubMed:23643382).1 Publication
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:614840
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06917793G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant rs121918124dbSNPEnsembl.1
Natural variantiVAR_072976137F → V in HH11. 1 Publication1
Natural variantiVAR_072977346M → V in HH11. 1 PublicationCorresponds to variant rs200148989dbSNPEnsembl.1
Natural variantiVAR_069178353P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant rs121918125dbSNPEnsembl.1
Natural variantiVAR_069963364R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant rs150288991dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi6870.
MalaCardsiTACR3.
MIMi614840. phenotype.
OpenTargetsiENSG00000169836.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA36304.

Chemistry databases

ChEMBLiCHEMBL4429.
GuidetoPHARMACOLOGYi362.

Polymorphism and mutation databases

BioMutaiTACR3.
DMDMi128364.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000698991 – 465Neuromedin-K receptorAdd BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...)Sequence analysis1
Glycosylationi50N-linked (GlcNAc...)Sequence analysis1
Glycosylationi73N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi158 ↔ 233PROSITE-ProRule annotation
Lipidationi374S-palmitoyl cysteineSequence analysis1

Post-translational modificationi

The anchoring of this receptor to the plasma membrane is probably mediated by the palmitoylation of a cysteine residue.

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP29371.
PRIDEiP29371.
TopDownProteomicsiP29371.

PTM databases

iPTMnetiP29371.
PhosphoSitePlusiP29371.

Expressioni

Gene expression databases

BgeeiENSG00000169836.
CleanExiHS_TACR3.
GenevisibleiP29371. HS.

Organism-specific databases

HPAiHPA009418.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TAC3Q9UHF02EBI-6655576,EBI-6655626

Protein-protein interaction databases

BioGridi112733. 1 interactor.
IntActiP29371. 1 interactor.
STRINGi9606.ENSP00000303325.

Chemistry databases

BindingDBiP29371.

Structurei

3D structure databases

ProteinModelPortaliP29371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4219. Eukaryota.
ENOG410XSC5. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000013018.
HOVERGENiHBG103412.
InParanoidiP29371.
KOiK04224.
OMAiVMTFAIC.
OrthoDBiEOG091G0WYG.
PhylomeDBiP29371.
TreeFamiTF315303.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001681. Neurokn_rcpt.
IPR001013. NK3_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01026. NEUROKININ3R.
PR00244. NEUROKININR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P29371-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATLPAAETW IDGGGGVGAD AVNLTASLAA GAATGAVETG WLQLLDQAGN
60 70 80 90 100
LSSSPSALGL PVASPAPSQP WANLTNQFVQ PSWRIALWSL AYGVVVAVAV
110 120 130 140 150
LGNLIVIWII LAHKRMRTVT NYFLVNLAFS DASMAAFNTL VNFIYALHSE
160 170 180 190 200
WYFGANYCRF QNFFPITAVF ASIYSMTAIA VDRYMAIIDP LKPRLSATAT
210 220 230 240 250
KIVIGSIWIL AFLLAFPQCL YSKTKVMPGR TLCFVQWPEG PKQHFTYHII
260 270 280 290 300
VIILVYCFPL LIMGITYTIV GITLWGGEIP GDTCDKYHEQ LKAKRKVVKM
310 320 330 340 350
MIIVVMTFAI CWLPYHIYFI LTAIYQQLNR WKYIQQVYLA SFWLAMSSTM
360 370 380 390 400
YNPIIYCCLN KRFRAGFKRA FRWCPFIKVS SYDELELKTT RFHPNRQSSM
410 420 430 440 450
YTVTRMESMT VVFDPNDADT TRSSRKKRAT PRDPSFNGCS RRNSKSASAT
460
SSFISSPYTS VDEYS
Length:465
Mass (Da):52,202
Last modified:December 1, 1992 - v1
Checksum:i98E88D4BC9DBD315
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3T → I in AAB21706 (PubMed:1312036).Curated1
Sequence conflicti63A → R in AAB21706 (PubMed:1312036).Curated1
Sequence conflicti439C → F in CAA46291 (PubMed:1312928).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06917793G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant rs121918124dbSNPEnsembl.1
Natural variantiVAR_072976137F → V in HH11. 1 Publication1
Natural variantiVAR_049422286K → R Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in FGFR1. 1 PublicationCorresponds to variant rs2276973dbSNPEnsembl.1
Natural variantiVAR_072977346M → V in HH11. 1 PublicationCorresponds to variant rs200148989dbSNPEnsembl.1
Natural variantiVAR_069178353P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant rs121918125dbSNPEnsembl.1
Natural variantiVAR_069963364R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant rs150288991dbSNPEnsembl.1
Natural variantiVAR_049423449A → T Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in SPRY4 or KAL1. 1 PublicationCorresponds to variant rs17033889dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M89473 mRNA. Translation: AAA36366.1.
S86392
, S86371, S86382, S86388, S86390 Genomic DNA. Translation: AAB21706.1.
X65172
, X65173, X65174, X65175, X65176 Genomic DNA. Translation: CAA46291.1.
AY462099 mRNA. Translation: AAR23926.1.
BC121806 mRNA. Translation: AAI21807.1.
CCDSiCCDS3664.1.
PIRiJQ1517.
RefSeqiNP_001050.1. NM_001059.2.
UniGeneiHs.942.

Genome annotation databases

EnsembliENST00000304883; ENSP00000303325; ENSG00000169836.
GeneIDi6870.
KEGGihsa:6870.
UCSCiuc003hxe.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M89473 mRNA. Translation: AAA36366.1.
S86392
, S86371, S86382, S86388, S86390 Genomic DNA. Translation: AAB21706.1.
X65172
, X65173, X65174, X65175, X65176 Genomic DNA. Translation: CAA46291.1.
AY462099 mRNA. Translation: AAR23926.1.
BC121806 mRNA. Translation: AAI21807.1.
CCDSiCCDS3664.1.
PIRiJQ1517.
RefSeqiNP_001050.1. NM_001059.2.
UniGeneiHs.942.

3D structure databases

ProteinModelPortaliP29371.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112733. 1 interactor.
IntActiP29371. 1 interactor.
STRINGi9606.ENSP00000303325.

Chemistry databases

BindingDBiP29371.
ChEMBLiCHEMBL4429.
GuidetoPHARMACOLOGYi362.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP29371.
PhosphoSitePlusiP29371.

Polymorphism and mutation databases

BioMutaiTACR3.
DMDMi128364.

Proteomic databases

PaxDbiP29371.
PRIDEiP29371.
TopDownProteomicsiP29371.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000304883; ENSP00000303325; ENSG00000169836.
GeneIDi6870.
KEGGihsa:6870.
UCSCiuc003hxe.2. human.

Organism-specific databases

CTDi6870.
DisGeNETi6870.
GeneCardsiTACR3.
GeneReviewsiTACR3.
HGNCiHGNC:11528. TACR3.
HPAiHPA009418.
MalaCardsiTACR3.
MIMi162332. gene.
614840. phenotype.
neXtProtiNX_P29371.
OpenTargetsiENSG00000169836.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA36304.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4219. Eukaryota.
ENOG410XSC5. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000013018.
HOVERGENiHBG103412.
InParanoidiP29371.
KOiK04224.
OMAiVMTFAIC.
OrthoDBiEOG091G0WYG.
PhylomeDBiP29371.
TreeFamiTF315303.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169836-MONOMER.
ReactomeiR-HSA-380095. Tachykinin receptors bind tachykinins.
R-HSA-416476. G alpha (q) signalling events.

Miscellaneous databases

GeneWikiiTachykinin_receptor_3.
GenomeRNAii6870.
PROiP29371.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169836.
CleanExiHS_TACR3.
GenevisibleiP29371. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001681. Neurokn_rcpt.
IPR001013. NK3_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01026. NEUROKININ3R.
PR00244. NEUROKININR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNK3R_HUMAN
AccessioniPrimary (citable) accession number: P29371
Secondary accession number(s): Q0P510
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: November 2, 2016
This is version 145 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  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.