Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia.
-
NTSR1-null mice are hyperthermic, do not lower body temperature after i.c.v. neurotensin, gain weight with higher food intake, lose NT-induced suppression of feeding and NT-induced hypolocomotion, but retain normal NT-induced analgesia.
"hyperthermic; their body temperature was not affected by intracerebroventricular"
Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception.
-
Comparing Ntsr1- and Ntsr2-deficient mice, altered hot-plate jump latency is seen only in Ntsr2 knockouts, assigning thermal nociception to Ntsr2 rather than Ntsr1.
"results suggest that Ntsr2 has an important role in thermal nociception compared"
Dimerization of the class A G protein-coupled neurotensin receptor NTS1 alters G protein interaction.
-
Purified NTS1 self-associates concentration-dependently, and monomers activate Galphaq-beta1-gamma2 while dimers exchange nucleotide with lower affinity, showing that dimerization is not a prerequisite for G protein activation.
"NTS1 monomers activate G alpha q beta(1)gamma(2), whereas receptor dimers"
-
Agonist neurotensin binding shifts from a Hill slope of ~1 at low receptor concentration to positive cooperativity (~2) at dimer-favouring concentrations.
"binds the agonist neurotensin with a"
Neurotensin receptor-1 inducible palmitoylation is required for efficient receptor-mediated mitogenic-signaling within structured membrane microdomains.
-
Human NTSR1 is dually palmitoylated at Cys381 and Cys383; the modification is required for caveolin-rich microdomain residence, Galphaq/11 coupling, NTS-induced ERK phosphorylation and protection from serum-starvation apoptosis.
"dual-palmitoylation at Cys381 and Cys383 of endogenously-expressed NTSR-1 in"
Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors.
-
Neurotensin acting through NTSR1 in human colonic epithelial and colon cancer cells induces miR-21 and miR-155 via NF-kB, suppressing PTEN, SOCS1 and PPP2CA, activating Akt and promoting xenograft tumour growth.
"NTR1 activation stimulates expression of miR-21 and miR-155 in"
Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties.
Conformational transitions of a neurotensin receptor 1-G(i1) complex.
-
Cryo-EM structures of human NTSR1 bound to agonist and heterotrimeric Gi1 reveal canonical and non-canonical (~45 degrees rotated) states of the receptor-G protein complex, and note that the receptor engages multiple G protein subtypes.
"present structures of human NTSR1 in complex with the agonist JMV449 and the"
Structure of the neurotensin receptor 1 in complex with β-arrestin 1.
-
Cryo-EM of full-length human NTSR1 with beta-arrestin 1 shows that receptor phosphorylation is required for a stable complex, with a PIP2 molecule bridging receptor TM1/TM4 and the arrestin C-lobe.
"phosphorylation of NTSR1 is critical for the"
β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.
-
The allosteric modulator SBI-553 is a beta-arrestin-biased NTSR1 agonist that selectively antagonizes the receptor's G protein signaling and attenuates psychostimulant self-administration without the side effects of balanced agonism, showing that the two arms produce separable physiological effects.
"selectively antagonizing G protein signaling"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
-
BioPlex 3.0 proteome-scale affinity-purification mass spectrometry reports an NTSR1-RAMP3 association among more than 118,000 interactions; the pair itself is reported in supplementary data rather than in the article text.
"of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162"
Allosteric modulation and G-protein selectivity of the Ca(2+)-sensing receptor.
-
NTSR1 is used as the reference promiscuous GPCR, activating most G protein subtypes, in G protein selectivity profiling.
"by CaSR were compared against G-protein subtype activation by NTSR1, a promiscuous GPCR that"
Multiplexed mapping of the interactome of GPCRs with receptor activity-modifying proteins.
-
A multiplexed suspension-bead-array screen of 215 GPCRs against the three RAMPs found 122 GPCRs with strong evidence for RAMP interaction; NTSR1-RAMP1 and NTSR1-RAMP3 pairs are reported in the supplementary tables.
"122 GPCRs that showed strong evidence for interaction with at least one RAMP"
Design of allosteric modulators that change GPCR G protein subtype selectivity.
Biased signaling at NTSR1 differentially regulates inhibitory synaptic transmission in the extended amygdala and suppresses motivated feeding in mice.
-
SBI-553, a beta-arrestin-biased NTSR1 modulator that attenuates Gq signaling, differentially modulates GABAergic neurotransmission across extended amygdala subregions and reduces palatable food consumption in mice.
"SBI-553 reduces palatable food consumption in both fed and food-deprived"
Ligand-dependent G protein dynamics underlying opioid efficacy.
-
smFRET of ternary complexes assembled from full-length human NTSR1 and Gi shows that agonist-dependent opening of the Galphai alpha-helical domain correlates with GTP turnover (R-squared 0.89), and that the allosteric modulator SBI-553 shifts the helical domain further open in proportion to its positive modulation of turnover.
"further shifted the AHD toward the open state proportionally to its positive modulation of GTP turnover in vitro"
-
The NTSR1 constructs used were human: full-length human NTSR1 expressed in Sf9 cells with an N-terminal Flag-8xHis tag and purified in the presence of NTS8-13.
"Full-length human NTSR1 was expressed and purified as previously described"
Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor.
-
Human NTSR1 cDNA cloned from the HT29 colonic adenocarcinoma line encodes a 418-residue seven-transmembrane receptor whose heterologous expression reconstitutes high-affinity neurotensin pharmacology; transcript is detected in brain, small intestine and blood mononuclear cells.
"amino acids with 7 transmembrane domains"
Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra.
-
High-affinity neurotensin receptor protein in rat substantia nigra is predominantly somatodendritic and extrasynaptic, with modest axonal labelling and an intracellular biosynthetic pool over smooth ER and Golgi membranes.
"labels with somata and dendrites of presumptive dopaminergic neurons"
Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
Neurotensin receptors can bind neurotensins
Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
The Ligand:GPCR:Gq complex dissociates
UniProtKB entry P30989 (NTSR1_HUMAN) flat file
-
UniProt types NTSR1 as the G protein-coupled receptor for the tridecapeptide neurotensin, signaling via G proteins that activate a phosphatidylinositol-calcium second messenger system, with MAP kinase activation and protection from apoptosis; locations are cell membrane and membrane raft, the latter requiring palmitoylation.
"G protein-coupled receptor for the tridecapeptide neurotensin"