Affinage

TACR3

Neuromedin-K receptor · UniProt P29371

Length
465 aa
Mass
52.2 kDa
Annotated
2026-04-28
100 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TACR3 encodes the neurokinin B receptor (NK3R), a Gq-coupled GPCR that is essential for hypothalamic GnRH pulse generation and reproductive maturation. Loss-of-function mutations in TACR3 cause normosmic congenital hypogonadotropic hypogonadism in humans, and pulsatile GnRH administration rescues gonadotropin secretion, placing NK3R upstream of GnRH neurons (PMID:19079066, PMID:20194706). NK3R activates inositol phosphate signaling via Gq-protein coupling; transmembrane domain mutations (Y256H, Y315C) disrupt receptor trafficking and abolish IP signaling, while the intracellular loop mutation R295S impairs Gq dissociation and exerts a dominant-negative effect on wild-type receptor function (PMID:24376026). In the central nervous system, NK3R acts upstream of arcuate kisspeptin (KNDy) neurons to trigger LH surges (PMID:27059932) and modulates neuronal excitability through CaMKII and AMPA receptor-dependent synaptic plasticity in the lateral habenula and hippocampus (PMID:32264959, PMID:38135756).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2008 High

    The fundamental question of whether neurokinin B signaling through NK3R is required for human reproduction was answered: loss-of-function TACR3 mutations cause congenital hypogonadotropic hypogonadism, establishing NK3R as a central gatekeeper of GnRH-dependent gonadal function.

    Evidence Homozygous loss-of-function mutations in TAC3/TACR3 identified across four consanguineous pedigrees with phenotypic characterization

    PMID:19079066

    Open questions at the time
    • Precise hypothalamic cell types expressing NK3R not yet identified
    • Mechanism by which NK3R controls GnRH pulse generation unknown
    • Whether defect is purely hypothalamic versus also pituitary not resolved
  2. 2010 High

    The question of where in the hypothalamic-pituitary-gonadal axis NK3R acts was resolved: pulsatile GnRH administration normalized LH release and restored fertility in TACR3-mutant patients, definitively placing NK3R upstream of the pituitary at the level of GnRH pulse generation, with evidence that the pathway's importance attenuates after early development.

    Evidence Pulsatile GnRH rescue in patients with TACR3 mutations; large-cohort sequencing (345 probands) with in vitro functional assays and longitudinal hormonal profiling showing reversibility of hypogonadotropism

    PMID:20194706 PMID:20332248

    Open questions at the time
    • Molecular mechanism of GnRH pulse frequency control by NK3R unresolved
    • Why the requirement for NKB signaling attenuates with age is unknown
    • No direct recordings from GnRH neurons in the context of NK3R disruption
  3. 2013 High

    The structure-function question of how disease-causing TACR3 mutations impair receptor signaling was answered at the molecular level: transmembrane mutations disrupt trafficking/stability and IP signaling, while an intracellular loop mutation traps Gq on the receptor and acts as a dominant-negative.

    Evidence Cell-based receptor quantification, IP signaling assays, FRET-based Gq-protein dissociation assay, and dominant-negative co-expression experiments

    PMID:24376026

    Open questions at the time
    • No structural data (crystal/cryo-EM) for NK3R to explain mutation effects at atomic resolution
    • Whether dominant-negative mechanism is relevant in heterozygous carriers in vivo is untested
    • Downstream effectors beyond Gq/IP pathway not fully characterized
  4. 2016 Medium

    The circuit-level question of how NK3R activation triggers GnRH/LH secretion was answered: NK3R in the retrochiasmatic area acts through arcuate kisspeptin (KNDy) neurons, and kisspeptin receptor antagonism completely blocks NK3R-induced LH surges, establishing the NK3R→kisspeptin→GnRH pathway hierarchy.

    Evidence Dual-label immunohistochemistry, intracerebroventricular kisspeptin receptor antagonist with NK3R agonist (senktide) in the ovine retrochiasmatic area

    PMID:27059932

    Open questions at the time
    • Whether NK3R acts directly on KNDy neurons or via interneurons is not resolved
    • Pathway architecture in humans not confirmed
    • Contribution of NK3R in other hypothalamic nuclei to pulsatile versus surge GnRH release unclear
  5. 2020 Medium

    Beyond reproduction, the question of whether NK3R modulates pain and affect circuits was addressed: Tacr3 overexpression in the lateral habenula suppresses nerve injury-induced neuronal hyperexcitability by reversing CaMKII phosphorylation, alleviating both allodynia and anxiety.

    Evidence AAV-mediated Tacr3 overexpression in mouse LHb, whole-cell patch clamp, p-CaMKII western blot, chemogenetic validation in a trigeminal neuralgia model

    PMID:32264959

    Open questions at the time
    • Whether endogenous NKB is the relevant ligand in LHb is not confirmed
    • Downstream targets of CaMKII mediating the anti-nociceptive effect are unknown
    • Relevance to human pain conditions untested
  6. 2023 Medium

    The question of how NK3R influences synaptic plasticity was clarified: hippocampal NK3R inhibition causes CaMKII hyperactivation and enhanced AMPA receptor phosphorylation, increasing dendritic spine density but impairing LTP, linking NK3R to homeostatic control of excitatory synaptic strength.

    Evidence Pharmacological TACR3 inhibition in rat hippocampus, multielectrode array, western blot for p-CaMKII/p-GluA1, LTP recordings in dentate gyrus, serum testosterone measurement

    PMID:38135756

    Open questions at the time
    • Whether synaptic effects are cell-autonomous or secondary to hormonal changes is not dissected
    • Identity of the endogenous NKB source in hippocampus is unknown
    • Behavioral consequences of hippocampal NK3R disruption not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the atomic-resolution structure of NK3R, the precise identity of NK3R-expressing cell types and their connectivity within the GnRH pulse generator, and whether the reproductive and synaptic plasticity functions of NK3R share common intracellular signaling logic.
  • No cryo-EM or crystal structure of NK3R
  • No single-cell resolution map of NK3R-expressing neurons in the human hypothalamus
  • Relationship between Gq/IP signaling and CaMKII/AMPA receptor modulation not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3
Partners
CAMK2AGNAQKISS1TAC3

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Loss-of-function mutations in TACR3 (encoding NK3R) cause severe congenital hypogonadotropin deficiency and pubertal failure in humans, establishing that neurokinin B signaling through NK3R is a critical central regulator of GnRH-dependent gonadal function. Human genetic analysis (homozygous loss-of-function mutations in TAC3/TACR3 in affected individuals from four pedigrees) with phenotypic characterization Nature genetics High 19079066
2010 TAC3/TACR3 mutations cause normosmic congenital hypogonadotropic hypogonadism of hypothalamic origin; pulsatile GnRH administration normalizes LH release and restores fertility, demonstrating that NK3R function is required upstream of the pituitary for GnRH pulse generation. Human genetic sequencing, splicing mutation functional validation, pulsatile GnRH administration in patients, hormonal profiling The Journal of clinical endocrinology and metabolism High 20194706
2010 TACR3 mutations are a relatively common cause of idiopathic hypogonadotropic hypogonadism; the neurokinin B pathway appears essential during early sexual development (neonatal life) but its importance in sustaining the hypothalamic-pituitary-gonadal axis attenuates over time, as shown by reversibility of hypogonadotropism after therapy discontinuation. Sequencing of TAC3/TACR3 in 345 probands, in vitro functional assays of identified variants, neuroendocrine phenotyping before and after hormone therapy The Journal of clinical endocrinology and metabolism High 20332248
2011 TACR3 missense mutation Tyr267Asn causes NK3R loss-of-function likely through protein misfolding; biallelic TAC3/TACR3 mutations lead to low GnRH pulsatile frequency manifesting as an elevated FSH/LH ratio and apulsatile LH profile with preserved alpha-subunit pulses, a specific neuroendocrine signature of NK3R pathway disruption. Molecular modeling, functional studies of missense variants, neuroendocrine phenotyping including LH pulse analysis, pulsatile GnRH challenge PloS one Medium 22031817
2013 Specific TACR3 missense mutations disrupt NK3R function through distinct mechanisms: Y256H and Y315C mutations in transmembrane domains 5 and 6 reduce receptor trafficking/stability and abolish inositol phosphate (IP) signaling, while R295S in the third intracellular loop impairs Gq-protein dissociation from the receptor after NKB binding, acting as a dominant-negative to also suppress wild-type NK3R signaling. In vitro cell-based assays (whole-cell and plasma membrane receptor quantification), IP signaling assays, FRET-based Gq-protein dissociation assay with NKB stimulation, dominant-negative co-expression experiments FASEB journal High 24376026
2012 TACR3 (NK3R) and its ligand neurokinin B are expressed in human female genital tract (uterus, ovary, oviduct), including in endometrial and oviductal epithelial cells and myometrium, suggesting a peripheral reproductive role for NK3R beyond hypothalamic GnRH regulation. RT-PCR and immunohistochemistry on fresh and archival tissue samples from reproductive-age and postmenopausal women Fertility and sterility Low 22424618
2011 In zebrafish, TAC3/TACR3 orthologs (TAC3a/b and TACR3a1/a2/b) are mainly expressed in brain regions; synthetic NKB-like peptides activate downstream signaling through zebrafish TACR3s in reporter assays, confirming conservation of TAC3/TACR3 system function in teleosts. cDNA cloning, tissue distribution studies, transcription reporter assays in eukaryotic cells Molecular and cellular endocrinology Medium 22580006
2020 Tacr3 in the lateral habenula (LHb) regulates orofacial allodynia and anxiety-like behaviors in a trigeminal neuralgia mouse model; AAV-mediated Tacr3 overexpression in the LHb suppresses nerve injury-induced hyperexcitability of LHb neurons by reversing pT-ION-induced upregulation of p-CaMKII, thereby alleviating both anxiety and allodynia. Mouse model of partial infraorbital nerve transection, AAV-mediated Tacr3 overexpression, whole-cell patch clamp recording, western blotting for p-CaMKII, chemogenetic inhibition (hM4D(Gi)) Acta neuropathologica communications Medium 32264959
2023 Hippocampal TACR3 is predominantly expressed in the cell membrane including the presynaptic compartment; inhibition of TACR3 activity causes hyperactivation of CaMKII and enhanced AMPA receptor phosphorylation leading to increased dendritic spine density and enhanced neural connectivity, while deficient TACR3 activity reduces serum testosterone and impairs LTP in the dentate gyrus, effects correctable by testosterone treatment. Rat model, immunofluorescence localization, pharmacological TACR3 inhibition, multielectrode array, western blot for CaMKII/AMPA receptor phosphorylation, LTP electrophysiology, hormone measurements Molecular psychiatry Medium 38135756
2016 NK3R activation in the retrochiasmatic area (RCh) triggers surge-like LH secretion that is mediated primarily through arcuate kisspeptin (KNDy) neurons; RCh senktide administration activates c-Fos in arcuate kisspeptin neurons, and kisspeptin receptor antagonism completely blocks the LH surge induced by RCh NK3R activation, placing NK3R upstream of kisspeptin in the GnRH/LH secretion pathway. Dual-label immunohistochemistry (kisspeptin/c-Fos), intracerebroventricular kisspeptin receptor antagonist infusion, NK3R agonist (senktide) administration into RCh, frequent blood sampling in ewes Journal of neuroendocrinology Medium 27059932
2011 NK3R (TACR3) is expressed in rat lymphatic muscle cells and mediates substance P-induced contractile (MLC20 phosphorylation) and pro-inflammatory (p38-MAPK, ERK1/2) signaling pathways; pharmacological inhibition of NK3R (along with NK1R) significantly reduces these downstream SP-mediated signals, and ERK1/2 and MLC20 phosphorylation are linked through PKC-dependent crosstalk. Rat mesenteric lymphatic muscle cell culture, pharmacological inhibition of NK1R and NK3R, phosphorylation assays for MLC20/p38-MAPK/ERK1/2, RT-PCR for receptor expression Microcirculation Medium 21166923
2014 Novel NK3R selective agonists with modified (E)-alkene dipeptide isostere backbone retain high potency at NK3R and exhibit resistance to proteolytic degradation, demonstrating that the peptidomimetic approach can generate stable NK3R agonists for in vivo use. Medicinal chemistry design, in vitro NK3R binding/activation assays, proteolytic stability assays Journal of medicinal chemistry Medium 25247671
2011 TACR3 promoter CpG methylation is decreased in the brain of marmoset monkeys after repeated cocaine-induced conditioned place preference, identifying TACR3 as a locus for epigenetic regulation in addiction-related neuroplasticity. DNA methylation analysis at TACR3 promoter CpG sites by bisulfite sequencing/pyrosequencing in marmosets after cocaine CPP paradigm Addiction biology Low 22070124
2020 NK3R is a G protein-coupled receptor belonging to the rhodopsin subfamily that functions by binding its high-affinity ligand neurokinin B (NKB), activating cellular signaling pathways; it is widely expressed in the nervous system from spinal cord to brain and is involved in GnRH regulation, mood disorders, chronic pain, learning and memory, and other neurological processes. Review summarizing receptor structure, G-protein coupling mechanism, and expression patterns established by prior experimental studies ACS chemical neuroscience Low 32926772

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nature genetics 654 19079066
1993 The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex. Annual review of immunology 430 8476574
1994 Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 371 8077657
1996 Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR-P1 cross-linking. The Journal of experimental medicine 296 8642351
1990 NKR-P1, a signal transduction molecule on natural killer cells. Science (New York, N.Y.) 252 2399464
1994 Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature 241 7969447
2005 Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. Journal of immunology (Baltimore, Md. : 1950) 222 16339513
2010 TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood. The Journal of clinical endocrinology and metabolism 193 20332248
2010 TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. The Journal of clinical endocrinology and metabolism 181 20194706
1991 cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6. Journal of immunology (Baltimore, Md. : 1950) 158 1680927
1992 Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. Journal of immunology (Baltimore, Md. : 1950) 157 1506685
2004 Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proceedings of the National Academy of Sciences of the United States of America 153 14990792
1998 CD161 (NKR-P1A) costimulation of CD1d-dependent activation of human T cells expressing invariant V alpha 24 J alpha Q T cell receptor alpha chains. The Journal of experimental medicine 142 9730888
2008 Functional consequences of interactions between human NKR-P1A and its ligand LLT1 expressed on activated dendritic cells and B cells. Journal of immunology (Baltimore, Md. : 1950) 132 18453569
1991 NKR-P1, an activating molecule on rat natural killer cells, stimulates phosphoinositide turnover and a rise in intracellular calcium. Journal of immunology (Baltimore, Md. : 1950) 128 1919012
2006 Expression of CD161 (NKR-P1A) defines subsets of human CD4 and CD8 T cells with different functional activities. Journal of immunology (Baltimore, Md. : 1950) 123 16365412
1997 Association with FcRgamma is essential for activation signal through NKR-P1 (CD161) in natural killer (NK) cells and NK1.1+ T cells. The Journal of experimental medicine 120 9396764
1995 NKR-P1A is a target-specific receptor that activates natural killer cell cytotoxicity. The Journal of experimental medicine 116 7722466
1991 Mouse NKR-P1. A family of genes selectively coexpressed in adherent lymphokine-activated killer cells. Journal of immunology (Baltimore, Md. : 1950) 116 1880421
1997 Rat spleen dendritic cells express natural killer cell receptor protein 1 (NKR-P1) and have cytotoxic activity to select targets via a Ca2+-dependent mechanism. The Journal of experimental medicine 113 9236200
2010 PGE2 inhibits natural killer and gamma delta T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling. Biochemical pharmacology 106 20470757
2012 Analysis of the expression of neurokinin B, kisspeptin, and their cognate receptors NK3R and KISS1R in the human female genital tract. Fertility and sterility 97 22424618
1996 Definition of a natural killer NKR-P1A+/CD56-/CD16- functionally immature human NK cell subset that differentiates in vitro in the presence of interleukin 12. The Journal of experimental medicine 85 8920872
2007 Cytomegalovirus evasion of innate immunity by subversion of the NKR-P1B:Clr-b missing-self axis. Immunity 77 17462921
2006 CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid sphingomyelinase. Journal of immunology (Baltimore, Md. : 1950) 72 16455998
1999 CD8(+)NKR-P1A (+)T cells preferentially accumulate in human liver. European journal of immunology 72 10458753
1992 Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1. Journal of immunology (Baltimore, Md. : 1950) 72 1517565
2011 Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations. PloS one 69 22031817
1999 Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function. Journal of immunology (Baltimore, Md. : 1950) 69 10229828
1994 Rat natural killer cell antigen, NKR-P1, related to C-type animal lectins is a carbohydrate-binding protein. The Journal of biological chemistry 68 8207018
2003 Urochordates and the origin of natural killer cells: identification of a CD94/NKR-P1-related receptor in blood cells of Botryllus. Proceedings of the National Academy of Sciences of the United States of America 67 12518047
1997 Lineage relationships and differentiation of natural killer (NK) T cells: intrathymic selection and interleukin (IL)-4 production in the absence of NKR-P1 and Ly49 molecules. The Journal of experimental medicine 55 9126920
2015 Identification, Characterization, and Three-Dimensional Structure of the Novel Circular Bacteriocin, Enterocin NKR-5-3B, from Enterococcus faecium. Biochemistry 53 26174911
2005 Diversity of NKR expression in aging T cells and in T cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Experimental gerontology 51 16002251
2014 Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems. Frontiers in immunology 49 24917862
2017 Study protocol for THINK: a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types. BMJ open 41 29133316
2012 The evolution of tachykinin/tachykinin receptor (TAC/TACR) in vertebrates and molecular identification of the TAC3/TACR3 system in zebrafish (Danio rerio). Molecular and cellular endocrinology 41 22580006
1999 The NKR-P1B gene product is an inhibitory receptor on SJL/J NK cells. Journal of immunology (Baltimore, Md. : 1950) 41 10229823
1994 Characterization and function of the NKR-P1dim/T cell receptor-alpha beta+ subset of rat T cells. Journal of immunology (Baltimore, Md. : 1950) 41 7506720
1997 Rat monocytes up-regulate NKR-P1A and down-modulate CD4 and CD43 during activation in vivo: monocyte subpopulations in normal and IFN-gamma-treated rats. Journal of leukocyte biology 40 9400815
2020 Tacr3 in the lateral habenula differentially regulates orofacial allodynia and anxiety-like behaviors in a mouse model of trigeminal neuralgia. Acta neuropathologica communications 39 32264959
2015 The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses. Blood 39 25612621
2012 Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders. Arquivos brasileiros de endocrinologia e metabologia 39 23329188
1998 Molecular characterization of rat NKR-P2, a lectin-like receptor expressed by NK cells and resting T cells. International immunology 39 9620593
2011 Isolation and characterization of enterocin W, a novel two-peptide lantibiotic produced by Enterococcus faecalis NKR-4-1. Applied and environmental microbiology 37 22138996
2006 NKR-P1 biology: from prototype to missing self. Immunologic research 36 17003506
2011 Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R. Microcirculation (New York, N.Y. : 1994) 35 21166923
2005 Functional requirements for signaling through the stimulatory and inhibitory mouse NKR-P1 (CD161) NK cell receptors. Journal of immunology (Baltimore, Md. : 1950) 34 15814704
2009 Two major groups of rat NKR-P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding. European journal of immunology 33 19130483
2006 The novel inhibitory NKR-P1C receptor and Ly49s3 identify two complementary, functionally distinct NK cell subsets in rats. Journal of immunology (Baltimore, Md. : 1950) 33 16547249
2018 Altered expression of the kisspeptin/KISS1R and neurokinin B/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome. Journal of assisted reproduction and genetics 32 30382469
1994 NKR-P1+ cells in the rat uterus: granulated metrial gland cells are of the natural killer cell lineage. Biology of reproduction 31 7803623
2015 Functional Analysis of Genes Involved in the Biosynthesis of Enterocin NKR-5-3B, a Novel Circular Bacteriocin. Journal of bacteriology 30 26503847
2011 Decreased methylation of the NK3 receptor coding gene (TACR3) after cocaine-induced place preference in marmoset monkeys. Addiction biology 30 22070124
2011 Molecular architecture of mouse activating NKR-P1 receptors. Journal of structural biology 28 21600988
2001 Toward an optimal oligosaccharide ligand for rat natural killer cell activation receptor NKR-P1. Biochemical and biophysical research communications 28 11549246
2001 Synthesis of chitooligomer-based glycoconjugates and their binding to the rat natural killer cell activation receptor NKR-P1. Glycoconjugate journal 28 12441671
2010 Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines. Journal of leukocyte biology 27 20395458
1997 The cytoplasmic domain of rat NKR-P1 receptor interacts with the N-terminal domain of p56(lck) via cysteine residues. European journal of immunology 27 9022000
2011 Phylogenetic and functional conservation of the NKR-P1F and NKR-P1G receptors in rat and mouse. Immunogenetics 25 21409442
2014 Gene cluster responsible for secretion of and immunity to multiple bacteriocins, the NKR-5-3 enterocins. Applied and environmental microbiology 24 25149515
2015 Modulation of Clr Ligand Expression and NKR-P1 Receptor Function during Murine Cytomegalovirus Infection. Journal of innate immunity 23 26044139
1997 Differential pathogenesis of lethal mousepox in congenic DBA/2 mice implicates natural killer cell receptor NKR-P1 in necrotizing hepatitis and the fifth component of complement in recruitment of circulating leukocytes to spleen. The American journal of pathology 23 9094996
2020 Tacr3/NK3R: Beyond Their Roles in Reproduction. ACS chemical neuroscience 21 32926772
2018 Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition. Nature communications 21 30397201
2016 Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection. Journal of immunology (Baltimore, Md. : 1950) 20 27511735
2014 Therapeutic potential of atorvastatin-modified dendritic cells in experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells and NKR-P1(+) cells. Journal of neuroimmunology 20 24565076
2011 High-level expression of soluble form of mouse natural killer cell receptor NKR-P1C(B6) in Escherichia coli. Protein expression and purification 20 21284957
2010 Structural analysis of natural killer cell receptor protein 1 (NKR-P1) extracellular domains suggests a conserved long loop region involved in ligand specificity. Journal of molecular modeling 20 20839018
2015 Four crystal structures of human LLT1, a ligand of human NKR-P1, in varied glycosylation and oligomerization states. Acta crystallographica. Section D, Biological crystallography 19 25760607
2012 Identification of enterocin NKR-5-3C, a novel class IIa bacteriocin produced by a multiple bacteriocin producer, Enterococcus faecium NKR-5-3. Bioscience, biotechnology, and biochemistry 19 22790957
2012 Mouse Clr-g, a ligand for NK cell activation receptor NKR-P1F: crystal structure and biophysical properties. Journal of immunology (Baltimore, Md. : 1950) 19 23071282
2009 A novel HIV-1 restriction factor that is biologically distinct from APOBEC3 cytidine deaminases in a human T cell line CEM.NKR. Retrovirology 19 19344514
1998 Phenotype of rat monocytes during acute kidney allograft rejection: increased expression of NKR-P1 and reduction of CD43. Scandinavian journal of immunology 19 9600314
1997 Association of human NK cell surface receptors NKR-P1 and CD94 with Src-family protein kinases. Immunogenetics 19 9211750
1994 Activation antigen expression on peripheral blood neutrophils following rat small bowel transplantation. NKR-P1 is a novel antigen preferentially expressed during allograft rejection. Transplantation 19 7940691
2022 Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse. Nature communications 18 36028489
2012 Evidence for Vpr-dependent HIV-1 replication in human CD4+ CEM.NKR T-cells. Retrovirology 18 23134572
2003 Expression cloning and function of the rat NK activating and inhibitory receptors NKR-P1A and -P1B. International immunology 18 12618485
2000 Cancer immunomodulation by carbohydrate ligands for the lymphocyte receptor NKR-P1. International journal of oncology 17 10639569
1997 NKR-P1A protein, an activating receptor of rat natural killer cells, binds to the chitobiose core of uncompletely glycosylated N-linked glycans, and to linear chitooligomers. Biochemical and biophysical research communications 17 9299469
2010 Hypothalamic dysfunction in a female with isolated hypogonadotropic hypogonadism and compound heterozygous TACR3 mutations and clinical manifestation in her heterozygous mother. Hormone research in paediatrics 16 20395662
2007 Cross-linking a mAb to NKR-P2/NKG2D on dendritic cells induces their activation and maturation leading to enhanced anti-tumor immune response. International immunology 16 17369187
2006 A novel EGFP-CEM-NKr flow cytometric method for measuring antibody dependent cell mediated-cytotoxicity (ADCC) activity in HIV-1 infected individuals. Journal of immunological methods 16 16884734
2004 Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: indicative of a common, innate, target-recognition paradigm? European journal of immunology 16 15048723
2023 Interplay between hippocampal TACR3 and systemic testosterone in regulating anxiety-associated synaptic plasticity. Molecular psychiatry 15 38135756
2017 Mutations near the cleavage site of enterocin NKR-5-3B prepeptide reveal new insights into its biosynthesis. Microbiology (Reading, England) 15 28113050
2016 Surge-Like Luteinising Hormone Secretion Induced by Retrochiasmatic Area NK3R Activation is Mediated Primarily by Arcuate Kisspeptin Neurones in the Ewe. Journal of neuroendocrinology 15 27059932
1997 NKR-P1A stimulation of arachidonate-generating enzymes in rat NK cells is associated with granule release and cytotoxic activity. Journal of immunology (Baltimore, Md. : 1950) 15 9200468
1996 NKR-P1+ cells localize selectively in Rat 9L gliosarcomas but have reduced cytolytic function. Cancer research 15 8758920
2022 Green tea catechin EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway. The Journal of nutritional biochemistry 14 35691596
2013 Structural model of lymphocyte receptor NKR-P1C revealed by mass spectrometry and molecular modeling. Analytical chemistry 14 23249299
2018 NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections. Cellular & molecular immunology 13 30275537
2012 A novel NKR-P1B(bright) NK cell subset expresses an activated CD25(+)CX(3)CR1(+)CD62L(-)CD11b(-)CD27(-) phenotype and is prevalent in blood, liver, and gut-associated lymphoid organs of rats. Journal of immunology (Baltimore, Md. : 1950) 13 22308308
2001 Homologues of natural killer cell receptors NKG2-D and NKR-P1 expressed in cattle. Veterinary immunology and immunopathology 13 11457486
1998 Rat NKR-P1+ CD3+ T cells: selective proliferation in interleukin-2, diverse T-cell-receptor-Vbeta repertoire and polarized interferon-gamma expression. Immunology 13 9767466
1997 Functional coupling of NKR-P1 receptors to various heterotrimeric G proteins in rat interleukin-2-activated natural killer cells. The Journal of biological chemistry 13 9395499
2014 Absence of GPR54 and TACR3 mutations in sporadic cases of idiopathic central precocious puberty. Hormone research in paediatrics 12 24434351
2014 Development of novel neurokinin 3 receptor (NK3R) selective agonists with resistance to proteolytic degradation. Journal of medicinal chemistry 12 25247671
2013 TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 12 24376026