NEUT_HUMAN
ID NEUT_HUMAN Reviewed; 170 AA.
AC P30990;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Neurotensin/neuromedin N;
DE Contains:
DE RecName: Full=Large neuromedin N;
DE AltName: Full=NmN-125;
DE Contains:
DE RecName: Full=Neuromedin N;
DE Short=NN;
DE Short=NmN;
DE Contains:
DE RecName: Full=Neurotensin;
DE Short=NT;
DE Contains:
DE RecName: Full=Tail peptide;
DE Flags: Precursor;
GN Name=NTS;
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].
RX PubMed=9530155; DOI=10.1152/ajpgi.1998.274.3.g535;
RA Dong Z., Wang X., Zhao Q., Townsend C.M. Jr., Evers B.M.;
RT "DNA methylation contributes to expression of the human
RT neurotensin/neuromedin N gene.";
RL Am. J. Physiol. 274:G535-G543(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-120.
RX PubMed=1436492; DOI=10.1016/0306-4522(92)90421-w;
RA Bean A.J., Dagerlind A., Hoekfelt T., Dobner P.R.;
RT "Cloning of human neurotensin/neuromedin N genomic sequences and expression
RT in the ventral mesencephalon of schizophrenics and age/sex matched
RT controls.";
RL Neuroscience 50:259-268(1992).
RN [4]
RP CLEAVAGE BY ACE AND MME.
RX PubMed=6208535; DOI=10.1016/0196-9781(84)90020-2;
RA Skidgel R.A., Engelbrecht S., Johnson A.R., Erdoes E.G.;
RT "Hydrolysis of substance p and neurotensin by converting enzyme and neutral
RT endopeptidase.";
RL Peptides 5:769-776(1984).
RN [5]
RP INTERACTION WITH SORL1.
RX PubMed=11294867; DOI=10.1074/jbc.m100857200;
RA Jacobsen L., Madsen P., Jacobsen C., Nielsen M.S., Gliemann J.,
RA Petersen C.M.;
RT "Activation and functional characterization of the mosaic receptor
RT SorLA/LR11.";
RL J. Biol. Chem. 276:22788-22796(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 151-163 IN COMPLEX WITH SORT1,
RP INTERACTION WITH SORT1, AND PYROGLUTAMATE FORMATION AT GLN-151.
RX PubMed=19122660; DOI=10.1038/nsmb.1543;
RA Quistgaard E.M., Madsen P., Groftehauge M.K., Nissen P., Petersen C.M.,
RA Thirup S.S.;
RT "Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller
RT domain.";
RL Nat. Struct. Mol. Biol. 16:96-98(2009).
RN [7]
RP STRUCTURE BY NMR OF 152-163 IN COMPLEX WITH NTSR1, AND SUBUNIT.
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: Neurotensin may play an endocrine or paracrine role in the
CC regulation of fat metabolism. It causes contraction of smooth muscle.
CC -!- SUBUNIT: Interacts with NTSR1 (PubMed:23140271). Interacts with SORT1
CC (PubMed:19122660). Interacts with SORL1 (PubMed:11294867).
CC {ECO:0000269|PubMed:11294867, ECO:0000269|PubMed:19122660,
CC ECO:0000269|PubMed:23140271}.
CC -!- INTERACTION:
CC P30990; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-6655799, EBI-11956541;
CC P30990; P30989: NTSR1; NbExp=2; IntAct=EBI-6655799, EBI-6655774;
CC PRO_0000019524; Q9BYF1: ACE2; NbExp=2; IntAct=EBI-6655817, EBI-7730807;
CC PRO_0000019524; P30989: NTSR1; NbExp=2; IntAct=EBI-6655817, EBI-6655774;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic vesicle, secretory vesicle.
CC Note=Packaged within secretory vesicles.
CC -!- PTM: [Neurotensin]: Neurotensin is cleaved and degraded by Angiotensin-
CC converting enzyme (ACE) and neprilysin (MME).
CC {ECO:0000269|PubMed:6208535}.
CC -!- SIMILARITY: Belongs to the neurotensin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Neurotensin entry;
CC URL="https://en.wikipedia.org/wiki/Neurotensin";
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DR EMBL; U91618; AAB50564.1; -; mRNA.
DR EMBL; BC010918; AAH10918.1; -; mRNA.
DR EMBL; S47339; AAB23934.1; -; Genomic_DNA.
DR CCDS; CCDS9029.1; -.
DR PIR; I58190; I58190.
DR RefSeq; NP_006174.1; NM_006183.4.
DR PDB; 2LNE; NMR; -; A=152-163.
DR PDB; 2LNF; NMR; -; A=152-163.
DR PDB; 2LNG; NMR; -; A=152-163.
DR PDB; 2LYW; NMR; -; B=152-163.
DR PDB; 2OYV; NMR; -; A=152-163.
DR PDB; 2OYW; NMR; -; A=152-163.
DR PDB; 3F6K; X-ray; 2.00 A; N=151-163.
DR PDB; 4PO7; X-ray; 2.66 A; N/P=151-163.
DR PDB; 5LUZ; X-ray; 2.70 A; C/D/P/Q=151-163.
DR PDB; 6UP7; EM; 4.20 A; C=158-163.
DR PDBsum; 2LNE; -.
DR PDBsum; 2LNF; -.
DR PDBsum; 2LNG; -.
DR PDBsum; 2LYW; -.
DR PDBsum; 2OYV; -.
DR PDBsum; 2OYW; -.
DR PDBsum; 3F6K; -.
DR PDBsum; 4PO7; -.
DR PDBsum; 5LUZ; -.
DR PDBsum; 6UP7; -.
DR AlphaFoldDB; P30990; -.
DR BMRB; P30990; -.
DR SMR; P30990; -.
DR BioGRID; 110976; 6.
DR DIP; DIP-60978N; -.
DR IntAct; P30990; 6.
DR STRING; 9606.ENSP00000256010; -.
DR BindingDB; P30990; -.
DR iPTMnet; P30990; -.
DR PhosphoSitePlus; P30990; -.
DR BioMuta; NTS; -.
DR DMDM; 2828196; -.
DR EPD; P30990; -.
DR jPOST; P30990; -.
DR MassIVE; P30990; -.
DR PaxDb; P30990; -.
DR PeptideAtlas; P30990; -.
DR PRIDE; P30990; -.
DR ProteomicsDB; 54756; -.
DR Antibodypedia; 29877; 303 antibodies from 27 providers.
DR DNASU; 4922; -.
DR Ensembl; ENST00000256010.7; ENSP00000256010.5; ENSG00000133636.11.
DR GeneID; 4922; -.
DR KEGG; hsa:4922; -.
DR MANE-Select; ENST00000256010.7; ENSP00000256010.5; NM_006183.5; NP_006174.1.
DR CTD; 4922; -.
DR DisGeNET; 4922; -.
DR GeneCards; NTS; -.
DR HGNC; HGNC:8038; NTS.
DR HPA; ENSG00000133636; Tissue enriched (intestine).
DR MIM; 162650; gene.
DR neXtProt; NX_P30990; -.
DR OpenTargets; ENSG00000133636; -.
DR PharmGKB; PA31820; -.
DR VEuPathDB; HostDB:ENSG00000133636; -.
DR eggNOG; ENOG502RYW6; Eukaryota.
DR GeneTree; ENSGT00640000091574; -.
DR HOGENOM; CLU_133874_0_0_1; -.
DR InParanoid; P30990; -.
DR OMA; WGLCSDS; -.
DR OrthoDB; 1378763at2759; -.
DR PhylomeDB; P30990; -.
DR TreeFam; TF330765; -.
DR PathwayCommons; P30990; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P30990; -.
DR SIGNOR; P30990; -.
DR BioGRID-ORCS; 4922; 9 hits in 1063 CRISPR screens.
DR ChiTaRS; NTS; human.
DR EvolutionaryTrace; P30990; -.
DR GeneWiki; Neurotensin; -.
DR GenomeRNAi; 4922; -.
DR Pharos; P30990; Tbio.
DR PRO; PR:P30990; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P30990; protein.
DR Bgee; ENSG00000133636; Expressed in nasal cavity epithelium and 127 other tissues.
DR ExpressionAtlas; P30990; baseline and differential.
DR Genevisible; P30990; HS.
DR GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005184; F:neuropeptide hormone activity; IEA:InterPro.
DR GO; GO:0071855; F:neuropeptide receptor binding; IPI:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:ARUK-UCL.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR InterPro; IPR008055; NeurotensiN.
DR PANTHER; PTHR15356; PTHR15356; 1.
DR Pfam; PF07421; Pro-NT_NN; 1.
DR PRINTS; PR01668; NEUROTENSIN.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal;
KW Vasoactive.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..148
FT /note="Large neuromedin N"
FT /id="PRO_0000019522"
FT PEPTIDE 144..148
FT /note="Neuromedin N"
FT /id="PRO_0000019523"
FT PEPTIDE 151..163
FT /note="Neurotensin"
FT /evidence="ECO:0000305|PubMed:6208535"
FT /id="PRO_0000019524"
FT PEPTIDE 166..170
FT /note="Tail peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000019525"
FT SITE 160..161
FT /note="Cleavage; by MME"
FT /evidence="ECO:0000269|PubMed:6208535"
FT SITE 161..162
FT /note="Cleavage; by ACE and MME"
FT /evidence="ECO:0000269|PubMed:6208535"
FT MOD_RES 151
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:19122660"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:4PO7"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:2LNF"
SQ SEQUENCE 170 AA; 19795 MW; 66E2E146DA08E3C7 CRC64;
MMAGMKIQLV CMLLLAFSSW SLCSDSEEEM KALEADFLTN MHTSKISKAH VPSWKMTLLN
VCSLVNNLNS PAEETGEVHE EELVARRKLP TALDGFSLEA MLTIYQLHKI CHSRAFQHWE
LIQEDILDTG NDKNGKEEVI KRKIPYILKR QLYENKPRRP YILKRDSYYY
