NTR1_HUMAN
ID NTR1_HUMAN Reviewed; 418 AA.
AC P30989; Q9H4H1; Q9H4T5;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 194.
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=NTRR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8381365; DOI=10.1016/0014-5793(93)81509-x;
RA Vita N., Laurent P., Lefort S., Chalon P., Dumont X., Kaghad M., Gully D.,
RA le Fur G., Ferrara P., Caput D.;
RT "Cloning and expression of a complementary DNA encoding a high affinity
RT human neurotensin receptor.";
RL FEBS Lett. 317:139-142(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=20048080; DOI=10.1158/0008-5472.can-09-1252;
RA Swift S.L., Burns J.E., Maitland N.J.;
RT "Altered expression of neurotensin receptors is associated with the
RT differentiation state of prostate cancer.";
RL Cancer Res. 70:347-356(2010).
RN [5]
RP FUNCTION, INTERACTION WITH GNA11, PALMITOYLATION AT CYS-381 AND CYS-383,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF CYS-381 AND
RP CYS-383.
RX PubMed=21725197; DOI=10.4161/cbt.12.5.15984;
RA Heakal Y., Woll M.P., Fox T., Seaton K., Levenson R., Kester M.;
RT "Neurotensin receptor-1 inducible palmitoylation is required for efficient
RT receptor-mediated mitogenic-signaling within structured membrane
RT microdomains.";
RL Cancer Biol. Ther. 12:427-435(2011).
RN [6]
RP STRUCTURE BY NMR OF 321-344 IN COMPLEX WITH NTS, AND FUNCTION.
RX PubMed=23140271; DOI=10.1080/07391102.2012.736776;
RA Da Costa G., Bondon A., Coutant J., Curmi P., Monti J.P.;
RT "Intermolecular interactions between the neurotensin and the third
RT extracellular loop of human neurotensin 1 receptor.";
RL J. Biomol. Struct. Dyn. 31:1381-1392(2013).
CC -!- FUNCTION: G-protein coupled receptor for the tridecapeptide neurotensin
CC (NTS) (PubMed:8381365, PubMed:21725197, PubMed:23140271). 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
CC (PubMed:21725197). {ECO:0000269|PubMed:21725197,
CC ECO:0000269|PubMed:23140271, ECO:0000269|PubMed:8381365}.
CC -!- SUBUNIT: Interacts (palmitoylated form) with GNA11.
CC {ECO:0000269|PubMed:21725197, ECO:0000269|PubMed:23140271}.
CC -!- INTERACTION:
CC P30989; P30990: NTS; NbExp=2; IntAct=EBI-6655774, EBI-6655799;
CC P30989; PRO_0000019524 [P30990]: NTS; NbExp=2; IntAct=EBI-6655774, EBI-6655817;
CC P30989; P30989: NTSR1; NbExp=2; IntAct=EBI-6655774, EBI-6655774;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8381365};
CC Multi-pass membrane protein {ECO:0000305}. Membrane raft
CC {ECO:0000269|PubMed:21725197}. Note=Palmitoylation is required for
CC localization at CAV1-enriched membrane rafts.
CC {ECO:0000269|PubMed:21725197}.
CC -!- TISSUE SPECIFICITY: Expressed in prostate (at protein level). Detected
CC in colon and peripheral blood mononuclear cells. Detected at very low
CC levels in brain. {ECO:0000269|PubMed:20048080,
CC ECO:0000269|PubMed:8381365}.
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:0000250|UniProtKB:P20789}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21725197}.
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:0000269|PubMed:21725197}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Neurotensin receptor subfamily. NTSR1 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Neurotensin receptor entry;
CC URL="https://en.wikipedia.org/wiki/Neurotensin_receptor";
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DR EMBL; X70070; CAA49675.1; -; mRNA.
DR EMBL; AY429106; AAR07901.1; -; mRNA.
DR EMBL; AL035669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS13502.1; -.
DR PIR; S29506; S29506.
DR RefSeq; NP_002522.2; NM_002531.2.
DR PDB; 2LYW; NMR; -; A=321-344.
DR PDB; 6OS9; EM; 3.00 A; R=20-418.
DR PDB; 6OSA; EM; 3.00 A; R=20-418.
DR PDB; 6PWC; EM; 4.90 A; R=49-418.
DR PDB; 6UP7; EM; 4.20 A; R=50-383.
DR PDBsum; 2LYW; -.
DR PDBsum; 6OS9; -.
DR PDBsum; 6OSA; -.
DR PDBsum; 6PWC; -.
DR PDBsum; 6UP7; -.
DR AlphaFoldDB; P30989; -.
DR SMR; P30989; -.
DR BioGRID; 110977; 118.
DR DIP; DIP-60977N; -.
DR IntAct; P30989; 3.
DR STRING; 9606.ENSP00000359532; -.
DR BindingDB; P30989; -.
DR ChEMBL; CHEMBL4123; -.
DR GuidetoPHARMACOLOGY; 309; -.
DR TCDB; 9.A.14.1.14; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P30989; 3 sites.
DR iPTMnet; P30989; -.
DR PhosphoSitePlus; P30989; -.
DR SwissPalm; P30989; -.
DR BioMuta; NTSR1; -.
DR DMDM; 62297312; -.
DR jPOST; P30989; -.
DR MassIVE; P30989; -.
DR MaxQB; P30989; -.
DR PaxDb; P30989; -.
DR PeptideAtlas; P30989; -.
DR PRIDE; P30989; -.
DR ProteomicsDB; 54755; -.
DR Antibodypedia; 1519; 332 antibodies from 31 providers.
DR DNASU; 4923; -.
DR Ensembl; ENST00000370501.4; ENSP00000359532.3; ENSG00000101188.5.
DR GeneID; 4923; -.
DR KEGG; hsa:4923; -.
DR MANE-Select; ENST00000370501.4; ENSP00000359532.3; NM_002531.3; NP_002522.2.
DR UCSC; uc002ydf.3; human.
DR CTD; 4923; -.
DR DisGeNET; 4923; -.
DR GeneCards; NTSR1; -.
DR HGNC; HGNC:8039; NTSR1.
DR HPA; ENSG00000101188; Group enriched (brain, intestine).
DR MIM; 162651; gene.
DR neXtProt; NX_P30989; -.
DR OpenTargets; ENSG00000101188; -.
DR PharmGKB; PA31821; -.
DR VEuPathDB; HostDB:ENSG00000101188; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244813; -.
DR HOGENOM; CLU_009579_6_5_1; -.
DR InParanoid; P30989; -.
DR OMA; CLCPLWG; -.
DR OrthoDB; 890529at2759; -.
DR PhylomeDB; P30989; -.
DR TreeFam; TF337167; -.
DR PathwayCommons; P30989; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P30989; -.
DR SIGNOR; P30989; -.
DR BioGRID-ORCS; 4923; 17 hits in 1067 CRISPR screens.
DR GeneWiki; Neurotensin_receptor_1; -.
DR GenomeRNAi; 4923; -.
DR Pharos; P30989; Tchem.
DR PRO; PR:P30989; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P30989; protein.
DR Bgee; ENSG00000101188; Expressed in muscle layer of sigmoid colon and 80 other tissues.
DR Genevisible; P30989; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032280; C:symmetric synapse; IEA:Ensembl.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0016492; F:G protein-coupled neurotensin receptor activity; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IEA:Ensembl.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0071545; P:inositol phosphate catabolic process; IEA:Ensembl.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051280; P:negative regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; IEA:Ensembl.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IEA:Ensembl.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; IEA:Ensembl.
DR GO; GO:0097151; P:positive regulation of inhibitory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IGI:ARUK-UCL.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0098900; P:regulation of action potential; IEA:Ensembl.
DR GO; GO:0003254; P:regulation of membrane depolarization; IEA:Ensembl.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IEA:Ensembl.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR GO; GO:0033993; P:response to lipid; IEA:Ensembl.
DR GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl.
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..418
FT /note="Neurotensin receptor type 1"
FT /id="PRO_0000069946"
FT TOPO_DOM 1..67
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 68..88
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 89..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 103..122
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 123..142
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 143..164
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 165..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 185..205
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 206..234
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 235..259
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 260..303
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 304..325
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 326..343
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TRANSMEM 344..364
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT TOPO_DOM 365..418
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P20789"
FT REGION 321..344
FT /note="Neurotensin binding"
FT /evidence="ECO:0000250"
FT LIPID 381
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:21725197"
FT LIPID 383
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:21725197"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 141..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 72
FT /note="A -> V (in dbSNP:rs11698783)"
FT /id="VAR_059328"
FT VARIANT 275
FT /note="Q -> H (in dbSNP:rs35373650)"
FT /id="VAR_049424"
FT VARIANT 304
FT /note="V -> I (in dbSNP:rs2273075)"
FT /id="VAR_020071"
FT MUTAGEN 381
FT /note="C->S: Abolishes palmitoylation; when associated with
FT S-383."
FT /evidence="ECO:0000269|PubMed:21725197"
FT MUTAGEN 383
FT /note="C->S: Abolishes palmitoylation; when associated with
FT S-381."
FT /evidence="ECO:0000269|PubMed:21725197"
FT CONFLICT 200
FT /note="A -> T (in Ref. 1; CAA49675)"
FT /evidence="ECO:0000305"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 60..90
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 98..127
FT /evidence="ECO:0007829|PDB:6OS9"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:6OSA"
FT HELIX 137..171
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 173..179
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 182..198
FT /evidence="ECO:0007829|PDB:6OS9"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:6OS9"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:6OS9"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:6OS9"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 230..244
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 246..271
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 296..328
FT /evidence="ECO:0007829|PDB:6OS9"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 336..365
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:6OS9"
FT HELIX 371..374
FT /evidence="ECO:0007829|PDB:6OS9"
SQ SEQUENCE 418 AA; 46259 MW; 471AD1C49D29C2C8 CRC64;
MRLNSSAPGT PGTPAADPFQ RAQAGLEEAL LAPGFGNASG NASERVLAAP SSELDVNTDI
YSKVLVTAVY LALFVVGTVG NTVTAFTLAR KKSLQSLQST VHYHLGSLAL SDLLTLLLAM
PVELYNFIWV HHPWAFGDAG CRGYYFLRDA CTYATALNVA SLSVERYLAI CHPFKAKTLM
SRSRTKKFIS AIWLASALLA VPMLFTMGEQ NRSADGQHAG GLVCTPTIHT ATVKVVIQVN
TFMSFIFPMV VISVLNTIIA NKLTVMVRQA AEQGQVCTVG GEHSTFSMAI EPGRVQALRH
GVRVLRAVVI AFVVCWLPYH VRRLMFCYIS DEQWTPFLYD FYHYFYMVTN ALFYVSSTIN
PILYNLVSAN FRHIFLATLA CLCPVWRRRR KRPAFSRKAD SVSSNHTLSS NATRETLY
