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   27-MAR-2024, entry version 174.
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";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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; 7.
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; 9606-ENSP00000256010; -.
DR   PeptideAtlas; P30990; -.
DR   ProteomicsDB; 54756; -.
DR   Antibodypedia; 29877; 350 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   AGR; HGNC:8038; -.
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; SWGLCSD; -.
DR   OrthoDB; 4248663at2759; -.
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; 10 hits in 1142 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 128 other cell types or tissues.
DR   ExpressionAtlas; P30990; baseline and differential.
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:0097746; P:blood vessel diameter maintenance; IEA:UniProtKB-KW.
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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:ARUK-UCL.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   InterPro; IPR008055; NeurotensiN.
DR   PANTHER; PTHR15356; NEUROTENSIN/NEUROMEDIN N; 1.
DR   PANTHER; PTHR15356:SF0; NEUROTENSIN_NEUROMEDIN N; 1.
DR   Pfam; PF07421; Pro-NT_NN; 1.
DR   PRINTS; PR01668; NEUROTENSIN.
DR   Genevisible; P30990; HS.
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
//