The length of NTSR1 gene is 53.93 Kb, including 4 exons and 3 introns.

Two transcripts are identified, a 4132 bp coding for a protein of 418 aa. The second contains 2950 bp but without yet identified coding protein.

NTSR1 (418 aa in human) belongs to the GPCR family containing 7 TM domains. Its structure contains 4 extracellular and intracellular loops, the N terminal amino acid extracellular part located in extra cellular region. Four glycosylation sites (extracellular) are reported as essential for the functions. The binding of neurotensin is depending on 6 aa of the 4^th extracellular loop of the protein (Vincent et al., 1999).

In central nervous system, NTSR1 is expressed in substantia nigra, ventral tegmental area, amygdal nucleus, striatum and entorrhinal and prefrontal cortices (Kanba at al., 1986; Nicot et al., 1994).
In extra cerebral region, NTSR1 was detected in small intestine (Seybold et al., 1990; Mendez et al., 1997), fundus of stomach (Huidobro-Toro et al., 1985), pancreas (Wang et al., 2000), fetal liver (Ehrenfried et al., 1994), colon (Mendez et al., 1997) uterine tissue (Rodriguez et al., 2010) and prostate (Swift et al., 2010).
NTSR1 expression in human cells was reported in prostatic cells (Swift et al., 2010), colonic epithelial cells (Martin et al., 2002), lymphocytes (Evers et al., 1994) including T (Magazin et al., 2004) and B lymphocytes (Saada et al., 2012).

In the cell membrane: Activation of NTSR1 through neurotensin binding needs some post translational events including glycosylation and palmitoylation to downstream heterotrimeric G protein subunits effectors. This lipidation allows its localization within cell membrane microdomains and enhances the interaction with Gαq /11 which mainly reside within structured microdomains. This NTSR-1-mediated MAPK signaling and cellular proliferation was demonstrated in breast cancer cells (Heakal et al., 2011).
Endocytosis: After activation by neurotensin, NTSR1 is desensitized through its internalization in endosomal vesicles in association with β-arrestin. This event requires phosphorylation depending on the C terminal region of NTSR1. Intracellular trafficking leads to NTSR1 degradation in lysosomes (Mazella and Vincent, 2006).

NTSR1 is activated by neurotensin binding through autocrine or paracrine mechanism. Several signalizations were described depending on cell lines.
Indeed, neurotensin induces Erk phosphorylation colonic HT29 cells through PLC activation leading to Inositol phosphate formation (Massa et al., 2011).
The recruitment of G protein was described through NTSR1 activation in microdomains (Heakal et al., 2011).
In other cell types, cell proliferation, migration and invasion are depending on a transactivation of EGFR by NTSR1 (Amorino et al., 2007; Moody et al., 2014 ) or act through the increase of expression and activation of EGFR, HER2, HER3 (Younes et al., 2014; Dupouy et al., 2014).

The NTSR1 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. 81 organisms have orthologs with human gene NTSR1.
Conservation during evolution:
NTSR1 gene is retrieved in jaw vertebrates (Gnathostomes) from the australian ghostshark, (Callorhinchus milii) to man, including most vertebrate groups (Teleosts, Coelacanth, the Amphibian Rana catesbeiana (Hwang et al., 2009), reptiles (python and lizard), birds and mammals. The duplication giving rise to NTSR1 and NTSR2 occurred probably in early vertebrates via the genome doubling (R2) events but details are unknown, as genes clearly encoding neurotensin receptors are doubtfully present in more basal vertebrates such as lampreys and hagfishes. Unlike its paralogue gene, NTSR1 was subject to positive selection in mammals, as numerous genes involved in chemosensory perception (Kosiol et al., 2008).