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P29371 (NK3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuromedin-K receptor

Short name=NKR
Alternative name(s):
NK-3 receptor
Short name=NK-3R
Neurokinin B receptor
Tachykinin receptor 3
Gene names
Name:TACR3
Synonyms:NK3R, TAC3R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Post-translational modification

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

Involvement in disease

Hypogonadotropic hypogonadism 11 with or without anosmia (HH11) [MIM:614840]: A 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).
Note: 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 (Ref.7). Ref.6 Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Hypogonadotropic hypogonadism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

hyperosmotic salinity response

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart rate

Inferred from electronic annotation. Source: Ensembl

positive regulation of uterine smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

regulation of dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of feeding behavior

Inferred from electronic annotation. Source: Ensembl

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to morphine

Inferred from electronic annotation. Source: Ensembl

tachykinin receptor signaling pathway

Traceable author statement PubMed 8990205. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

dendrite membrane

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

neuronal cell body membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 23597562. Source: IntAct

tachykinin receptor activity

Traceable author statement PubMed 8990205. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TAC3Q9UHF02EBI-6655576,EBI-6655626

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465Neuromedin-K receptor
PRO_0000069899

Regions

Topological domain1 – 8484Extracellular Potential
Transmembrane85 – 10723Helical; Name=1; Potential
Topological domain108 – 11710Cytoplasmic Potential
Transmembrane118 – 13922Helical; Name=2; Potential
Topological domain140 – 15920Extracellular Potential
Transmembrane160 – 18122Helical; Name=3; Potential
Topological domain182 – 20120Cytoplasmic Potential
Transmembrane202 – 22221Helical; Name=4; Potential
Topological domain223 – 24523Extracellular Potential
Transmembrane246 – 27025Helical; Name=5; Potential
Topological domain271 – 29929Cytoplasmic Potential
Transmembrane300 – 32122Helical; Name=6; Potential
Topological domain322 – 33413Extracellular Potential
Transmembrane335 – 35925Helical; Name=7; Potential
Topological domain360 – 465106Cytoplasmic Potential

Amino acid modifications

Lipidation3741S-palmitoyl cysteine Potential
Glycosylation231N-linked (GlcNAc...) Potential
Glycosylation501N-linked (GlcNAc...) Potential
Glycosylation731N-linked (GlcNAc...) Potential
Disulfide bond158 ↔ 233 By similarity

Natural variations

Natural variant931G → D in HH11; unequivocal evidence of impaired receptor signaling. Ref.6
Corresponds to variant rs121918124 [ dbSNP | Ensembl ].
VAR_069177
Natural variant2861K → R Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in FGFR1. Ref.7
Corresponds to variant rs2276973 [ dbSNP | Ensembl ].
VAR_049422
Natural variant3531P → S in HH11; unequivocal evidence of impaired receptor signaling. Ref.6
Corresponds to variant rs121918125 [ dbSNP | Ensembl ].
VAR_069178
Natural variant3641R → Q in HH11; the patient also carries a mutation in FGFR1. Ref.7
VAR_069963
Natural variant4491A → T Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in SPRY4 or KAL1. Ref.7
Corresponds to variant rs17033889 [ dbSNP | Ensembl ].
VAR_049423

Experimental info

Sequence conflict31T → I in AAB21706. Ref.2
Sequence conflict631A → R in AAB21706. Ref.2
Sequence conflict4391C → F in CAA46291. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P29371 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 98E88D4BC9DBD315

FASTA46552,202
        10         20         30         40         50         60 
MATLPAAETW IDGGGGVGAD AVNLTASLAA GAATGAVETG WLQLLDQAGN LSSSPSALGL 

        70         80         90        100        110        120 
PVASPAPSQP WANLTNQFVQ PSWRIALWSL AYGVVVAVAV LGNLIVIWII LAHKRMRTVT 

       130        140        150        160        170        180 
NYFLVNLAFS DASMAAFNTL VNFIYALHSE WYFGANYCRF QNFFPITAVF ASIYSMTAIA 

       190        200        210        220        230        240 
VDRYMAIIDP LKPRLSATAT KIVIGSIWIL AFLLAFPQCL YSKTKVMPGR TLCFVQWPEG 

       250        260        270        280        290        300 
PKQHFTYHII VIILVYCFPL LIMGITYTIV GITLWGGEIP GDTCDKYHEQ LKAKRKVVKM 

       310        320        330        340        350        360 
MIIVVMTFAI CWLPYHIYFI LTAIYQQLNR WKYIQQVYLA SFWLAMSSTM YNPIIYCCLN 

       370        380        390        400        410        420 
KRFRAGFKRA FRWCPFIKVS SYDELELKTT RFHPNRQSSM YTVTRMESMT VVFDPNDADT 

       430        440        450        460 
TRSSRKKRAT PRDPSFNGCS RRNSKSASAT SSFISSPYTS VDEYS 

« Hide

References

« Hide 'large scale' references
[1]"cDNA sequence and heterologous expression of the human neurokinin-3 receptor."
Huang R.-R.C., Cheung A.H., Mazina K.E., Strader C.D., Fong T.M.
Biochem. Biophys. Res. Commun. 184:966-972(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Molecular characterisation, expression and localisation of human neurokinin-3 receptor."
Buell G., Schulz M.F., Arkinstall S.J., Maury K., Missotten M., Adami N., Talabot F., Kawashima E.
FEBS Lett. 299:90-95(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The primary structure and gene organization of human substance P and neuromedin K receptors."
Takahashi K., Tanaka A., Hara M., Nakanishi S.
Eur. J. Biochem. 204:1025-1033(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[4]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"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].
[6]"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: VARIANTS HH11 ASP-93 AND SER-353, CHARACTERIZATION OF VARIANTS HH11 ASP-93 AND SER-353.
[7]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HH11 GLN-364, VARIANTS ARG-286 AND THR-449.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M89473 mRNA. Translation: AAA36366.1.
S86392 expand/collapse EMBL AC list , S86371, S86382, S86388, S86390 Genomic DNA. Translation: AAB21706.1.
X65172 expand/collapse EMBL AC list , X65173, X65174, X65175, X65176 Genomic DNA. Translation: CAA46291.1.
AY462099 mRNA. Translation: AAR23926.1.
BC121806 mRNA. Translation: AAI21807.1.
CCDSCCDS3664.1.
PIRJQ1517.
RefSeqNP_001050.1. NM_001059.2.
UniGeneHs.942.

3D structure databases

ProteinModelPortalP29371.
SMRP29371. Positions 87-368.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112733. 1 interaction.
IntActP29371. 1 interaction.
STRING9606.ENSP00000303325.

Chemistry

BindingDBP29371.
ChEMBLCHEMBL4429.
GuidetoPHARMACOLOGY362.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP29371.

Polymorphism databases

DMDM128364.

Proteomic databases

PaxDbP29371.
PRIDEP29371.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304883; ENSP00000303325; ENSG00000169836.
GeneID6870.
KEGGhsa:6870.
UCSCuc003hxe.1. human.

Organism-specific databases

CTD6870.
GeneCardsGC04M104507.
GeneReviewsTACR3.
HGNCHGNC:11528. TACR3.
HPAHPA009418.
MIM162332. gene.
614840. phenotype.
neXtProtNX_P29371.
Orphanet478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBPA36304.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG331485.
HOGENOMHOG000013018.
HOVERGENHBG103412.
InParanoidP29371.
KOK04224.
OMAPTRQSSM.
OrthoDBEOG7N37FW.
PhylomeDBP29371.
TreeFamTF315303.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP29371.
CleanExHS_TACR3.
GenevestigatorP29371.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001681. Neurokn_rcpt.
IPR001013. NK3_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01026. NEUROKININ3R.
PR00244. NEUROKININR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTachykinin_receptor_3.
GenomeRNAi6870.
NextBio26817.
PROP29371.
SOURCESearch...

Entry information

Entry nameNK3R_HUMAN
AccessionPrimary (citable) accession number: P29371
Secondary accession number(s): Q0P510
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries