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P29371

- NK3R_HUMAN

UniProt

P29371 - NK3R_HUMAN

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Protein

Neuromedin-K receptor

Gene

TACR3

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. tachykinin receptor activity Source: ProtInc

GO - Biological processi

  1. aging Source: Ensembl
  2. hyperosmotic salinity response Source: Ensembl
  3. positive regulation of blood pressure Source: Ensembl
  4. positive regulation of heart rate Source: Ensembl
  5. positive regulation of uterine smooth muscle contraction Source: Ensembl
  6. regulation of dopamine metabolic process Source: Ensembl
  7. regulation of feeding behavior Source: Ensembl
  8. response to cocaine Source: Ensembl
  9. response to estradiol Source: Ensembl
  10. response to morphine Source: Ensembl
  11. tachykinin receptor signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16963. Tachykinin receptors bind tachykinins.
REACT_18283. 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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:11528. TACR3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8484ExtracellularSequence AnalysisAdd
BLAST
Transmembranei85 – 10723Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini108 – 11710CytoplasmicSequence Analysis
Transmembranei118 – 13922Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini140 – 15920ExtracellularSequence AnalysisAdd
BLAST
Transmembranei160 – 18122Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini182 – 20120CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei202 – 22221Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini223 – 24523ExtracellularSequence AnalysisAdd
BLAST
Transmembranei246 – 27025Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini271 – 29929CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei300 – 32122Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini322 – 33413ExtracellularSequence AnalysisAdd
BLAST
Transmembranei335 – 35925Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini360 – 465106CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. dendrite membrane Source: Ensembl
  3. integral component of plasma membrane Source: ProtInc
  4. neuronal cell body membrane Source: Ensembl
  5. nucleus Source: Ensembl
  6. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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).2 Publications
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 (PubMed:23643382).1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 Publication
Corresponds to variant rs121918124 [ dbSNP | Ensembl ].
VAR_069177
Natural varianti353 – 3531P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 Publication
Corresponds to variant rs121918125 [ dbSNP | Ensembl ].
VAR_069178
Natural varianti364 – 3641R → Q in HH11; the patient also carries a mutation in FGFR1. 1 Publication
VAR_069963

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 465465Neuromedin-K receptorPRO_0000069899Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi50 – 501N-linked (GlcNAc...)Sequence Analysis
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi158 ↔ 233PROSITE-ProRule annotation
Lipidationi374 – 3741S-palmitoyl cysteineSequence Analysis

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.

PTM databases

PhosphoSiteiP29371.

Expressioni

Gene expression databases

BgeeiP29371.
CleanExiHS_TACR3.
GenevestigatoriP29371.

Organism-specific databases

HPAiHPA009418.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112733. 1 interaction.
IntActiP29371. 1 interaction.
STRINGi9606.ENSP00000303325.

Structurei

3D structure databases

ProteinModelPortaliP29371.
SMRiP29371. Positions 87-368.
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

eggNOGiNOG331485.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000013018.
HOVERGENiHBG103412.
InParanoidiP29371.
KOiK04224.
OMAiPTRQSSM.
OrthoDBiEOG7N37FW.
PhylomeDBiP29371.
TreeFamiTF315303.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31T → I in AAB21706. (PubMed:1312036)Curated
Sequence conflicti63 – 631A → R in AAB21706. (PubMed:1312036)Curated
Sequence conflicti439 – 4391C → F in CAA46291. (PubMed:1312928)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931G → D in HH11; unequivocal evidence of impaired receptor signaling. 1 Publication
Corresponds to variant rs121918124 [ dbSNP | Ensembl ].
VAR_069177
Natural varianti286 – 2861K → R Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in FGFR1. 1 Publication
Corresponds to variant rs2276973 [ dbSNP | Ensembl ].
VAR_049422
Natural varianti353 – 3531P → S in HH11; unequivocal evidence of impaired receptor signaling. 1 Publication
Corresponds to variant rs121918125 [ dbSNP | Ensembl ].
VAR_069178
Natural varianti364 – 3641R → Q in HH11; the patient also carries a mutation in FGFR1. 1 Publication
VAR_069963
Natural varianti449 – 4491A → T Polymorphism that may contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in SPRY4 or KAL1. 1 Publication
Corresponds to variant rs17033889 [ dbSNP | Ensembl ].
VAR_049423

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.1. human.

Polymorphism databases

DMDMi128364.

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 .
CCDSi CCDS3664.1.
PIRi JQ1517.
RefSeqi NP_001050.1. NM_001059.2.
UniGenei Hs.942.

3D structure databases

ProteinModelPortali P29371.
SMRi P29371. Positions 87-368.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112733. 1 interaction.
IntActi P29371. 1 interaction.
STRINGi 9606.ENSP00000303325.

Chemistry

BindingDBi P29371.
ChEMBLi CHEMBL4429.
GuidetoPHARMACOLOGYi 362.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P29371.

Polymorphism databases

DMDMi 128364.

Proteomic databases

PaxDbi P29371.
PRIDEi P29371.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000304883 ; ENSP00000303325 ; ENSG00000169836 .
GeneIDi 6870.
KEGGi hsa:6870.
UCSCi uc003hxe.1. human.

Organism-specific databases

CTDi 6870.
GeneCardsi GC04M104507.
GeneReviewsi TACR3.
HGNCi HGNC:11528. TACR3.
HPAi HPA009418.
MIMi 162332. gene.
614840. phenotype.
neXtProti NX_P29371.
Orphaneti 478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBi PA36304.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG331485.
GeneTreei ENSGT00760000118781.
HOGENOMi HOG000013018.
HOVERGENi HBG103412.
InParanoidi P29371.
KOi K04224.
OMAi PTRQSSM.
OrthoDBi EOG7N37FW.
PhylomeDBi P29371.
TreeFami TF315303.

Enzyme and pathway databases

Reactomei REACT_16963. Tachykinin receptors bind tachykinins.
REACT_18283. G alpha (q) signalling events.

Miscellaneous databases

GeneWikii Tachykinin_receptor_3.
GenomeRNAii 6870.
NextBioi 26817.
PROi P29371.
SOURCEi Search...

Gene expression databases

Bgeei P29371.
CleanExi HS_TACR3.
Genevestigatori P29371.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001681. Neurokn_rcpt.
IPR001013. NK3_rcpt.
[Graphical view ]
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PR01026. NEUROKININ3R.
PR00244. NEUROKININR.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: VARIANT HH11 GLN-364, VARIANTS ARG-286 AND THR-449.

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: October 29, 2014
This is version 131 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

External Data

Dasty 3