NTR1_RAT
ID NTR1_RAT Reviewed; 424 AA.
AC P20789;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Neurotensin receptor type 1;
DE Short=NT-R-1;
DE Short=NTR1;
DE AltName: Full=High-affinity levocabastine-insensitive neurotensin receptor;
DE AltName: Full=NTRH;
GN Name=Ntsr1; Synonyms=Ntsr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1694443; DOI=10.1016/0896-6273(90)90137-5;
RA Tanaka K., Masu M., Nakanishi S.;
RT "Structure and functional expression of the cloned rat neurotensin
RT receptor.";
RL Neuron 4:847-854(1990).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 43-396 IN COMPLEX WITH NEUROTENSIN
RP FRAGMENT, LIGAND BINDING DOMAIN, AND DISULFIDE BOND.
RX PubMed=23051748; DOI=10.1038/nature11558;
RA White J.F., Noinaj N., Shibata Y., Love J., Kloss B., Xu F.,
RA Gvozdenovic-Jeremic J., Shah P., Shiloach J., Tate C.G., Grisshammer R.;
RT "Structure of the agonist-bound neurotensin receptor.";
RL Nature 490:508-513(2012).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 50-390 IN COMPLEX WITH
RP NEUROTENSIN FRAGMENT, DISULFIDE BOND, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP FUNCTION.
RX PubMed=24453215; DOI=10.1073/pnas.1317903111;
RA Egloff P., Hillenbrand M., Klenk C., Batyuk A., Heine P., Balada S.,
RA Schlinkmann K.M., Scott D.J., Schutz M., Pluckthun A.;
RT "Structure of signaling-competent neurotensin receptor 1 obtained by
RT directed evolution in Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E655-E662(2014).
RN [4] {ECO:0007744|PDB:4XEE, ECO:0007744|PDB:4XES}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 43-396, FUNCTION, SUBCELLULAR
RP LOCATION, TOPOLOGY, DISULFIDE BONDS, DOMAIN, AND MUTAGENESIS OF GLU-166;
RP LEU-310 AND PHE-358.
RX PubMed=26205105; DOI=10.1038/ncomms8895;
RA Krumm B.E., White J.F., Shah P., Grisshammer R.;
RT "Structural prerequisites for G-protein activation by the neurotensin
RT receptor.";
RL Nat. Commun. 6:7895-7895(2015).
CC -!- FUNCTION: G-protein coupled receptor for the tridecapeptide neurotensin
CC (NTS) (PubMed:23051748, PubMed:24453215, PubMed:26205105). Signaling is
CC effected via G proteins that activate a phosphatidylinositol-calcium
CC second messenger system. Signaling leads to the activation of
CC downstream MAP kinases and protects cells against apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:P30989, ECO:0000269|PubMed:1694443,
CC ECO:0000269|PubMed:23051748, ECO:0000269|PubMed:24453215,
CC ECO:0000269|PubMed:26205105}.
CC -!- SUBUNIT: Interacts (palmitoylated form) with GNA11.
CC {ECO:0000250|UniProtKB:P30989}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1694443,
CC ECO:0000269|PubMed:24453215, ECO:0000269|PubMed:26205105}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:1694443,
CC ECO:0000269|PubMed:24453215, ECO:0000269|PubMed:26205105}. Membrane
CC raft {ECO:0000250|UniProtKB:P30989}. Note=Palmitoylation is required
CC for localization at CAV1-enriched membrane rafts.
CC {ECO:0000250|UniProtKB:P30989}.
CC -!- TISSUE SPECIFICITY: Detected in brain and small intestine.
CC {ECO:0000269|PubMed:1694443}.
CC -!- DOMAIN: The ligand binding pocket consists mainly of extracellular
CC loops ECL2 and ECL3, as well as transmembrane regions TM6 and TM7.
CC {ECO:0000269|PubMed:23051748, ECO:0000269|PubMed:26205105}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P30989}.
CC -!- PTM: Palmitoylated; this is required for normal localization at
CC membrane rafts and normal GNA11-mediated activation of down-stream
CC signaling cascades. The palmitoylation level increases in response to
CC neurotensin treatment. {ECO:0000250|UniProtKB:P30989}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Neurotensin receptor subfamily. NTSR1 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR PIR; JH0164; JH0164.
DR RefSeq; NP_001102437.1; NM_001108967.1.
DR RefSeq; XP_006235850.1; XM_006235788.1.
DR PDB; 3ZEV; X-ray; 3.00 A; A/B=50-390.
DR PDB; 4BUO; X-ray; 2.75 A; A/B=50-390.
DR PDB; 4BV0; X-ray; 3.10 A; A/B=50-390.
DR PDB; 4BWB; X-ray; 3.57 A; A/B=50-390.
DR PDB; 4GRV; X-ray; 2.80 A; A=43-268, A=300-396.
DR PDB; 4XEE; X-ray; 2.90 A; A=43-396.
DR PDB; 4XES; X-ray; 2.60 A; A=43-396.
DR PDB; 5T04; X-ray; 3.30 A; A=43-268, A=297-396.
DR PDB; 6YVR; X-ray; 2.46 A; AAA/BBB=50-371.
DR PDB; 6Z4Q; X-ray; 2.92 A; AAA=50-371.
DR PDB; 6Z4S; X-ray; 2.71 A; AAA=50-371.
DR PDB; 6Z4V; X-ray; 2.60 A; AAA=50-371.
DR PDB; 6Z66; X-ray; 3.19 A; AAA=50-371.
DR PDB; 6Z8N; X-ray; 2.80 A; AAA=50-371.
DR PDB; 6ZA8; X-ray; 2.72 A; AAA=50-371.
DR PDB; 6ZIN; X-ray; 2.64 A; AAA=50-371.
DR PDB; 7L0P; EM; 4.10 A; C=50-390.
DR PDB; 7L0Q; EM; 4.30 A; C=50-390.
DR PDB; 7L0R; EM; 4.20 A; C=50-390.
DR PDB; 7L0S; EM; 4.50 A; C=50-390.
DR PDBsum; 3ZEV; -.
DR PDBsum; 4BUO; -.
DR PDBsum; 4BV0; -.
DR PDBsum; 4BWB; -.
DR PDBsum; 4GRV; -.
DR PDBsum; 4XEE; -.
DR PDBsum; 4XES; -.
DR PDBsum; 5T04; -.
DR PDBsum; 6YVR; -.
DR PDBsum; 6Z4Q; -.
DR PDBsum; 6Z4S; -.
DR PDBsum; 6Z4V; -.
DR PDBsum; 6Z66; -.
DR PDBsum; 6Z8N; -.
DR PDBsum; 6ZA8; -.
DR PDBsum; 6ZIN; -.
DR PDBsum; 7L0P; -.
DR PDBsum; 7L0Q; -.
DR PDBsum; 7L0R; -.
DR PDBsum; 7L0S; -.
DR AlphaFoldDB; P20789; -.
DR SMR; P20789; -.
DR DIP; DIP-59956N; -.
DR IntAct; P20789; 2.
DR STRING; 10116.ENSRNOP00000035997; -.
DR BindingDB; P20789; -.
DR ChEMBL; CHEMBL3027; -.
DR GuidetoPHARMACOLOGY; 309; -.
DR GlyGen; P20789; 3 sites.
DR iPTMnet; P20789; -.
DR PhosphoSitePlus; P20789; -.
DR SwissPalm; P20789; -.
DR PaxDb; P20789; -.
DR Ensembl; ENSRNOT00000039780; ENSRNOP00000035997; ENSRNOG00000028708.
DR GeneID; 366274; -.
DR KEGG; rno:366274; -.
DR UCSC; RGD:1306076; rat.
DR CTD; 4923; -.
DR RGD; 1306076; Ntsr1.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244813; -.
DR HOGENOM; CLU_009579_6_5_1; -.
DR InParanoid; P20789; -.
DR OMA; CLCPLWG; -.
DR OrthoDB; 890529at2759; -.
DR PhylomeDB; P20789; -.
DR TreeFam; TF337167; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:P20789; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000028708; Expressed in ovary and 13 other tissues.
DR Genevisible; P20789; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0044309; C:neuron spine; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0032280; C:symmetric synapse; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0016492; F:G protein-coupled neurotensin receptor activity; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IDA:RGD.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0071545; P:inositol phosphate catabolic process; IMP:RGD.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IDA:RGD.
DR GO; GO:0007612; P:learning; IMP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; IMP:RGD.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; IMP:RGD.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IMP:RGD.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; IMP:RGD.
DR GO; GO:0097151; P:positive regulation of inhibitory postsynaptic potential; IMP:RGD.
DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; IMP:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IMP:RGD.
DR GO; GO:0098900; P:regulation of action potential; IDA:RGD.
DR GO; GO:0003254; P:regulation of membrane depolarization; IMP:RGD.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IMP:RGD.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:RGD.
DR GO; GO:0033993; P:response to lipid; IDA:RGD.
DR GO; GO:0001659; P:temperature homeostasis; IMP:RGD.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003985; NT1_rcpt.
DR InterPro; IPR003984; NT_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01479; NEUROTENSINR.
DR PRINTS; PR01480; NEUROTENSN1R.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..424
FT /note="Neurotensin receptor type 1"
FT /id="PRO_0000069948"
FT TOPO_DOM 1..68
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 69..89
FT /note="Helical; Name=1"
FT TOPO_DOM 90..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 104..123
FT /note="Helical; Name=2"
FT TOPO_DOM 124..143
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 144..165
FT /note="Helical; Name=3"
FT TOPO_DOM 166..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 186..206
FT /note="Helical; Name=4"
FT TOPO_DOM 207..235
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 236..260
FT /note="Helical; Name=5"
FT TOPO_DOM 261..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 309..330
FT /note="Helical; Name=6"
FT TOPO_DOM 331..348
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:24453215"
FT TRANSMEM 349..369
FT /note="Helical; Name=7"
FT TOPO_DOM 370..424
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24453215"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..349
FT /note="Neurotensin binding"
FT REGION 397..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..424
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 386
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P30989"
FT LIPID 388
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P30989"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 142..225
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:23051748, ECO:0000269|PubMed:24453215"
FT MUTAGEN 166
FT /note="E->A: Abolishes signaling via G-proteins; when
FT associated with A-310 and A-358."
FT /evidence="ECO:0000269|PubMed:26205105"
FT MUTAGEN 310
FT /note="L->A: Abolishes signaling via G-proteins; when
FT associated with A-166 and A-358."
FT /evidence="ECO:0000269|PubMed:26205105"
FT MUTAGEN 358
FT /note="F->A: Abolishes signaling via G-proteins; when
FT associated with A-166 and A-310."
FT /evidence="ECO:0000269|PubMed:26205105"
FT TURN 51..55
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 61..92
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 97..119
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 121..127
FT /evidence="ECO:0007829|PDB:4XES"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 138..172
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 174..180
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 183..200
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 203..207
FT /evidence="ECO:0007829|PDB:4XES"
FT STRAND 208..212
FT /evidence="ECO:0007829|PDB:4XES"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4XES"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 231..245
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 247..267
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 301..333
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 341..368
FT /evidence="ECO:0007829|PDB:4XES"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:4XES"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:4XES"
SQ SEQUENCE 424 AA; 47055 MW; A9C2F7EAF8D9BCD3 CRC64;
MHLNSSVPQG TPGEPDAQPF SGPQSEMEAT FLALSLSNGS GNTSESDTAG PNSDLDVNTD
IYSKVLVTAI YLALFVVGTV GNSVTAFTLA RKKSLQSLQS TVHYHLGSLA LSDLLILLLA
MPVELYNFIW VHHPWAFGDA GCRGYYFLRD ACTYATALNV ASLSVERYLA ICHPFKAKTL
MSRSRTKKFI SAIWLASALL AIPMLFTMGL QNRSGDGTHP GGLVCTPIVD TATVKVVIQV
NTFMSFLFPM LVISILNTVI ANKLTVMVHQ AAEQGRVCTV GTHNGLEHST FNMTIEPGRV
QALRHGVLVL RAVVIAFVVC WLPYHVRRLM FCYISDEQWT TFLFDFYHYF YMLTNALFYV
SSAINPILYN LVSANFRQVF LSTLACLCPG WRHRRKKRPT FSRKPNSMSS NHAFSTSATR
ETLY
