The human CARTPT gene spans 1886 base pairs and includes three exons and two introns (Douglass and Daoud, 1996).

Transcription of the 1886 base pair (bp) long CARTPT gene including three exons, yields a 933 bases CARTPT mRNA, which in turn is translated into the 116 amino acid (aa) long prepro-CART peptide. The first 27 amino acid residues serve as a hydrophobic N-terminal signal sequence, which is cleaved, resulting in the 89 aa long pro-CART peptide (Douglass et al., 1995). Pro-CART is subsequently subject to processing by prohormone/proprotein convertases (PCs) during the regulated secretory pathway in the Golgi apparatus, immature secretory granules and finally mature secretory granules (Stein et al., 2006b). PC1/3 is primarily responsible for producing the intermediate peptide 10-89, whereas PC2 and to a lesser extent PC5/6A generate the two bioactive CART peptides (42-89 and 49-89) (Stein et al., 2006a; Stein et al., 2006b). In addition, there are a number of smaller CART peptide fragments of uncertain importance (Kuhar and Yoho, 1999; Dylag et al., 2006; Stein et al., 2006b).

Prepro-CART is a 116 aa long peptide with a molecular weight of 12829 Da. As described above, posttranslational modifications yield an 89 aa long pro-CART peptide (28-116) and eventually two bioactive CART peptides (42-89 and 49-89).

CART peptides have been found in the central, peripheral and enteric nervous systems, and also in endocrine cells in the pancreatic islets (Jensen et al., 1999; Wierup et al., 2004; Wierup and Sundler, 2006), the GI tract mucosa (Ekblad et al., 2003), the thyroid (Wierup et al., 2007), and the adrenal medulla (Dun et al., 2006).

CART is localized to the secretory granules of neuroendocrine cells as demonstrated in rat pancreatic β-cells (Wierup et al., 2006).

CART peptide is a brain-gut peptide, acting both as a neurotransmitter and as a hormone. Within the CNS, the spatial distribution of CART peptides together with various experimental studies suggest a role of CART peptides in regulating food intake and body weight (Kuhar et al., 1999; Rogge et al., 2008) with an overall anorexigenic effect via largely unknown mechanisms (Hunter et al., 2004; Rogge et al., 2008). This is also supported by observations that CARTPT null mice and humans carrying a mutated CARTPT gene develop obesity and signs of type 2 diabetes (Asnicar et al., 2001; del Giudice et al., 2001; Guérardel et al., 2005; Wierup et al., 2005). In addition, there is evidence of CART involvement in other brain processes such as mechanisms of reward and stress response (Kuhar et al., 1999; Jaworski et al., 2006; Rogge et al., 2008).
Hormonal expression of CART in pancreatic islets occurs mainly in somatostatin-producing δ-cells (Jensen et al., 1999; Wierup and Sundler, 2006), and the produced CART peptides participate in the regulation of insulin, glucagon, and somatostatin secretion (Wierup and Sundler, 2006; Wierup et al., 2006). Indeed, CART is necessary for normal islet function, since Cart null mice have diminished insulin secretion and reduced glucose elimination (Wierup et al., 2005). Interestingly, there is recent evidence that CART is crucial for pancreatic islet β-cell viability, both by reducing apoptosis and by increasing proliferation via several different pathways (Sathanoori et al., 2013).
Within the GI tract mucosa, CART expression has been identified mainly in gastrin-producing G-cells (Ekblad et al., 2003). The physiological function of CART in the enteric neurons and GI endocrine cells remains poorly elucidated (Ekblad, 2006).

CART is highly conserved between species. The amino acid sequence is 95% identical between humans, rats and mice (Douglass and Daoud, 1996; Stein et al., 2006b). Goldfish pro-CART peptide is 40-50% homologous to the mammalian counterpart, with 70-80% homology in the biologically active C-terminal portions of the peptide (Volkoff and Peter, 2001).

A missense mutation resulting in the substitution of Leu with Phe at codon 34, within the NH2-terminal CART region, was identified in an Italian family. Heterozygosity for this mutation was associated with severe obesity within the family and was not found in controls. Resting metabolic rates were lower than expected in subjects with the mutation (del Giudice et al., 2001).
A SNP within the CARTPT gene (SNP-3608T>C (rs7379701/rs4703647)) has been demonstrated to possibly contribute to the genetic risk for obesity (Guérardel et al., 2005).