UniProtKB - P29371 (NK3R_HUMAN)
Protein
Neuromedin-K receptor
Gene
TACR3
Organism
Homo sapiens (Human)
Status
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
- aging Source: Ensembl
- G protein-coupled receptor signaling pathway Source: Reactome
- hyperosmotic salinity response Source: Ensembl
- positive regulation of blood pressure Source: Ensembl
- positive regulation of flagellated sperm motility Source: UniProtKB
- positive regulation of heart rate Source: Ensembl
- positive regulation of uterine smooth muscle contraction Source: Ensembl
- regulation of dopamine metabolic process Source: Ensembl
- regulation of feeding behavior Source: Ensembl
- response to cocaine Source: Ensembl
- response to estradiol Source: Ensembl
- response to morphine Source: Ensembl
- tachykinin receptor signaling pathway Source: ProtInc
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
PathwayCommonsi | P29371 |
Reactomei | R-HSA-380095, Tachykinin receptors bind tachykinins R-HSA-416476, G alpha (q) signalling events |
SIGNORi | P29371 |
Names & Taxonomyi
Protein namesi | Recommended name: Neuromedin-K receptorShort 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000169836.4 |
HGNCi | HGNC:11528, TACR3 |
MIMi | 162332, gene |
neXtProti | NX_P29371 |
Subcellular locationi
Plasma membrane
Nucleus
- nucleus Source: Ensembl
Plasma Membrane
- dendrite membrane Source: Ensembl
- integral component of plasma membrane Source: ProtInc
- neuronal cell body membrane Source: Ensembl
- plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: Ensembl
- sperm midpiece Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 84 | ExtracellularSequence analysisAdd BLAST | 84 | |
Transmembranei | 85 – 107 | Helical; Name=1Sequence analysisAdd BLAST | 23 | |
Topological domaini | 108 – 117 | CytoplasmicSequence analysis | 10 | |
Transmembranei | 118 – 139 | Helical; Name=2Sequence analysisAdd BLAST | 22 | |
Topological domaini | 140 – 159 | ExtracellularSequence analysisAdd BLAST | 20 | |
Transmembranei | 160 – 181 | Helical; Name=3Sequence analysisAdd BLAST | 22 | |
Topological domaini | 182 – 201 | CytoplasmicSequence analysisAdd BLAST | 20 | |
Transmembranei | 202 – 222 | Helical; Name=4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 223 – 245 | ExtracellularSequence analysisAdd BLAST | 23 | |
Transmembranei | 246 – 270 | Helical; Name=5Sequence analysisAdd BLAST | 25 | |
Topological domaini | 271 – 299 | CytoplasmicSequence analysisAdd BLAST | 29 | |
Transmembranei | 300 – 321 | Helical; Name=6Sequence analysisAdd BLAST | 22 | |
Topological domaini | 322 – 334 | ExtracellularSequence analysisAdd BLAST | 13 | |
Transmembranei | 335 – 359 | Helical; Name=7Sequence analysisAdd BLAST | 25 | |
Topological domaini | 360 – 465 | CytoplasmicSequence analysisAdd BLAST | 106 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & 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).
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069177 | 93 | G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918124EnsemblClinVar. | 1 | |
Natural variantiVAR_072976 | 137 | F → V in HH11. 1 Publication | 1 | |
Natural variantiVAR_072977 | 346 | M → V in HH11. 1 PublicationCorresponds to variant dbSNP:rs200148989Ensembl. | 1 | |
Natural variantiVAR_069178 | 353 | P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918125EnsemblClinVar. | 1 | |
Natural variantiVAR_069963 | 364 | R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs150288991Ensembl. | 1 |
Keywords - Diseasei
Disease mutation, Hypogonadotropic hypogonadismOrganism-specific databases
DisGeNETi | 6870 |
GeneReviewsi | TACR3 |
MalaCardsi | TACR3 |
MIMi | 614840, phenotype |
OpenTargetsi | ENSG00000169836 |
Orphaneti | 478, Kallmann syndrome 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA36304 |
Miscellaneous databases
Pharosi | P29371, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4429 |
DrugBanki | DB04872, Osanetant DB11692, Pavinetant DB06429, Talnetant |
DrugCentrali | P29371 |
GuidetoPHARMACOLOGYi | 362 |
Polymorphism and mutation databases
BioMutai | TACR3 |
DMDMi | 128364 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000069899 | 1 – 465 | Neuromedin-K receptorAdd BLAST | 465 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 23 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 50 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 73 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 158 ↔ 233 | PROSITE-ProRule annotation | ||
Lipidationi | 374 | S-palmitoyl cysteineSequence analysis | 1 |
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, PalmitateProteomic databases
PaxDbi | P29371 |
PeptideAtlasi | P29371 |
PRIDEi | P29371 |
ProteomicsDBi | 54552 |
TopDownProteomicsi | P29371 |
PTM databases
GlyGeni | P29371, 3 sites |
iPTMneti | P29371 |
PhosphoSitePlusi | P29371 |
Expressioni
Gene expression databases
Bgeei | ENSG00000169836, Expressed in calcaneal tendon and 30 other tissues |
Genevisiblei | P29371, HS |
Organism-specific databases
HPAi | ENSG00000169836, Tissue enhanced (brain, urinary bladder) |
Interactioni
Binary interactionsi
P29371
With | #Exp. | IntAct |
---|---|---|
Neurokinin-B (PRO_0000033566) | 2 | EBI-6655576,EBI-6655626 |
Protein-protein interaction databases
BioGRIDi | 112733, 72 interactors |
IntActi | P29371, 1 interactor |
STRINGi | 9606.ENSP00000303325 |
Chemistry databases
BindingDBi | P29371 |
Miscellaneous databases
RNActi | P29371, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4219, Eukaryota |
GeneTreei | ENSGT00940000153745 |
HOGENOMi | CLU_009579_6_1_1 |
InParanoidi | P29371 |
OMAi | PQCLYSI |
OrthoDBi | 715197at2759 |
PhylomeDBi | P29371 |
TreeFami | TF315303 |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR001681, Neurokn_rcpt IPR001013, NK3_rcpt |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01026, NEUROKININ3R PR00244, NEUROKININR |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P29371-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 3 | T → I in AAB21706 (PubMed:1312036).Curated | 1 | |
Sequence conflicti | 63 | A → R in AAB21706 (PubMed:1312036).Curated | 1 | |
Sequence conflicti | 439 | C → F in CAA46291 (PubMed:1312928).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069177 | 93 | G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918124EnsemblClinVar. | 1 | |
Natural variantiVAR_072976 | 137 | F → V in HH11. 1 Publication | 1 | |
Natural variantiVAR_049422 | 286 | K → 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_072977 | 346 | M → V in HH11. 1 PublicationCorresponds to variant dbSNP:rs200148989Ensembl. | 1 | |
Natural variantiVAR_069178 | 353 | P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 PublicationCorresponds to variant dbSNP:rs121918125EnsemblClinVar. | 1 | |
Natural variantiVAR_069963 | 364 | R → Q in HH11; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs150288991Ensembl. | 1 | |
Natural variantiVAR_049423 | 449 | A → 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 |
CCDSi | CCDS3664.1 |
PIRi | JQ1517 |
RefSeqi | NP_001050.1, NM_001059.2 |
Genome annotation databases
Ensembli | ENST00000304883; ENSP00000303325; ENSG00000169836 |
GeneIDi | 6870 |
KEGGi | hsa:6870 |
UCSCi | uc003hxe.2, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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 |
CCDSi | CCDS3664.1 |
PIRi | JQ1517 |
RefSeqi | NP_001050.1, NM_001059.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 112733, 72 interactors |
IntActi | P29371, 1 interactor |
STRINGi | 9606.ENSP00000303325 |
Chemistry databases
BindingDBi | P29371 |
ChEMBLi | CHEMBL4429 |
DrugBanki | DB04872, Osanetant DB11692, Pavinetant DB06429, Talnetant |
DrugCentrali | P29371 |
GuidetoPHARMACOLOGYi | 362 |
Protein family/group databases
GPCRDBi | Search... |
PTM databases
GlyGeni | P29371, 3 sites |
iPTMneti | P29371 |
PhosphoSitePlusi | P29371 |
Polymorphism and mutation databases
BioMutai | TACR3 |
DMDMi | 128364 |
Proteomic databases
PaxDbi | P29371 |
PeptideAtlasi | P29371 |
PRIDEi | P29371 |
ProteomicsDBi | 54552 |
TopDownProteomicsi | P29371 |
Protocols and materials databases
Antibodypediai | 1543, 356 antibodies |
Genome annotation databases
Ensembli | ENST00000304883; ENSP00000303325; ENSG00000169836 |
GeneIDi | 6870 |
KEGGi | hsa:6870 |
UCSCi | uc003hxe.2, human |
Organism-specific databases
CTDi | 6870 |
DisGeNETi | 6870 |
EuPathDBi | HostDB:ENSG00000169836.4 |
GeneCardsi | TACR3 |
GeneReviewsi | TACR3 |
HGNCi | HGNC:11528, TACR3 |
HPAi | ENSG00000169836, Tissue enhanced (brain, urinary bladder) |
MalaCardsi | TACR3 |
MIMi | 162332, gene 614840, phenotype |
neXtProti | NX_P29371 |
OpenTargetsi | ENSG00000169836 |
Orphaneti | 478, Kallmann syndrome 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA36304 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4219, Eukaryota |
GeneTreei | ENSGT00940000153745 |
HOGENOMi | CLU_009579_6_1_1 |
InParanoidi | P29371 |
OMAi | PQCLYSI |
OrthoDBi | 715197at2759 |
PhylomeDBi | P29371 |
TreeFami | TF315303 |
Enzyme and pathway databases
PathwayCommonsi | P29371 |
Reactomei | R-HSA-380095, Tachykinin receptors bind tachykinins R-HSA-416476, G alpha (q) signalling events |
SIGNORi | P29371 |
Miscellaneous databases
BioGRID-ORCSi | 6870, 2 hits in 847 CRISPR screens |
ChiTaRSi | TACR3, human |
GeneWikii | Tachykinin_receptor_3 |
GenomeRNAii | 6870 |
Pharosi | P29371, Tchem |
PROi | PR:P29371 |
RNActi | P29371, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000169836, Expressed in calcaneal tendon and 30 other tissues |
Genevisiblei | P29371, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM IPR001681, Neurokn_rcpt IPR001013, NK3_rcpt |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR00237, GPCRRHODOPSN PR01026, NEUROKININ3R PR00244, NEUROKININR |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NK3R_HUMAN | |
Accessioni | P29371Primary (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: | December 2, 2020 | |
This is version 169 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries