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Protein

Neuromedin-K receptor

Gene

TACR3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: GO_Central

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

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:
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

EuPathDBiHostDB:ENSG00000169836.4
HGNCiHGNC:11528 TACR3
MIMi162332 gene
neXtProtiNX_P29371

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 dbSNP:rs121918124EnsemblClinVar.1
Natural variantiVAR_072976137F → V in HH11. 1 Publication1
Natural variantiVAR_072977346M → V in HH11. 1 PublicationCorresponds to variant dbSNP:rs200148989Ensembl.1
Natural variantiVAR_069178353P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918125EnsemblClinVar.1
Natural variantiVAR_069963364R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs150288991Ensembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi6870
GeneReviewsiTACR3
MalaCardsiTACR3
MIMi614840 phenotype
OpenTargetsiENSG00000169836
Orphaneti478 Kallmann syndrome
432 Normosmic congenital hypogonadotropic hypogonadism
PharmGKBiPA36304

Chemistry databases

ChEMBLiCHEMBL4429
DrugBankiDB04872 Osanetant
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...) asparagineSequence analysis1
Glycosylationi50N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi73N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi54552
TopDownProteomicsiP29371

PTM databases

iPTMnetiP29371
PhosphoSitePlusiP29371

Expressioni

Gene expression databases

BgeeiENSG00000169836 Expressed in 20 organ(s), highest expression level in hypothalamus
CleanExiHS_TACR3
GenevisibleiP29371 HS

Organism-specific databases

HPAiHPA009418

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112733, 72 interactors
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
GeneTreeiENSGT00930000150872
HOGENOMiHOG000013018
HOVERGENiHBG103412
InParanoidiP29371
KOiK04224
OMAiMYTLTRM
OrthoDBiEOG091G0WYG
PhylomeDBiP29371
TreeFamiTF315303

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001681 Neurokn_rcpt
IPR001013 NK3_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01026 NEUROKININ3R
PR00244 NEUROKININR
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 dbSNP:rs121918124EnsemblClinVar.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 dbSNP:rs2276973EnsemblClinVar.1
Natural variantiVAR_072977346M → V in HH11. 1 PublicationCorresponds to variant dbSNP:rs200148989Ensembl.1
Natural variantiVAR_069178353P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918125EnsemblClinVar.1
Natural variantiVAR_069963364R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs150288991Ensembl.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 dbSNP:rs17033889EnsemblClinVar.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

Similar proteinsi

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, 72 interactors
IntActiP29371, 1 interactor
STRINGi9606.ENSP00000303325

Chemistry databases

BindingDBiP29371
ChEMBLiCHEMBL4429
DrugBankiDB04872 Osanetant
GuidetoPHARMACOLOGYi362

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP29371
PhosphoSitePlusiP29371

Polymorphism and mutation databases

BioMutaiTACR3
DMDMi128364

Proteomic databases

PaxDbiP29371
PRIDEiP29371
ProteomicsDBi54552
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
EuPathDBiHostDB:ENSG00000169836.4
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
GeneTreeiENSGT00930000150872
HOGENOMiHOG000013018
HOVERGENiHBG103412
InParanoidiP29371
KOiK04224
OMAiMYTLTRM
OrthoDBiEOG091G0WYG
PhylomeDBiP29371
TreeFamiTF315303

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiTachykinin_receptor_3
GenomeRNAii6870
PROiPR:P29371
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169836 Expressed in 20 organ(s), highest expression level in hypothalamus
CleanExiHS_TACR3
GenevisibleiP29371 HS

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001681 Neurokn_rcpt
IPR001013 NK3_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01026 NEUROKININ3R
PR00244 NEUROKININR
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNK3R_HUMAN
AccessioniPrimary (citable) accession number: P29371
Secondary accession number(s): Q0P510
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: November 7, 2018
This is version 156 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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