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P29371

- NK3R_HUMAN

UniProt

P29371 - NK3R_HUMAN

Protein

Neuromedin-K receptor

Gene

TACR3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Dec 1992)
      Previous versions | rss
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    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. protein binding Source: IntAct
    2. 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

    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

    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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8484ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini108 – 11710CytoplasmicSequence Analysis
    Topological domaini140 – 15920ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini182 – 20120CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini223 – 24523ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini271 – 29929CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini322 – 33413ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini360 – 465106CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei85 – 10723Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei118 – 13922Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei160 – 18122Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei202 – 22221Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei246 – 27025Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei300 – 32122Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei335 – 35925Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG331485.
    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

    MATLPAAETW IDGGGGVGAD AVNLTASLAA GAATGAVETG WLQLLDQAGN    50
    LSSSPSALGL PVASPAPSQP WANLTNQFVQ PSWRIALWSL AYGVVVAVAV 100
    LGNLIVIWII LAHKRMRTVT NYFLVNLAFS DASMAAFNTL VNFIYALHSE 150
    WYFGANYCRF QNFFPITAVF ASIYSMTAIA VDRYMAIIDP LKPRLSATAT 200
    KIVIGSIWIL AFLLAFPQCL YSKTKVMPGR TLCFVQWPEG PKQHFTYHII 250
    VIILVYCFPL LIMGITYTIV GITLWGGEIP GDTCDKYHEQ LKAKRKVVKM 300
    MIIVVMTFAI CWLPYHIYFI LTAIYQQLNR WKYIQQVYLA SFWLAMSSTM 350
    YNPIIYCCLN KRFRAGFKRA FRWCPFIKVS SYDELELKTT RFHPNRQSSM 400
    YTVTRMESMT VVFDPNDADT TRSSRKKRAT PRDPSFNGCS RRNSKSASAT 450
    SSFISSPYTS VDEYS 465
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    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

    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 1, 2014
    This is version 130 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