Can1p

Can1p is a transmembrane protein found in the plasma membrane of the yeast Saccharomyces cerevisiae. It functions as a cationic amino acid permease, mediating the uptake of positively charged amino acids such as arginine, lysine and histidine. The protein belongs to the Amino Acid-Polyamine-Organocation (APC) superfamily, characterized by 12 predicted transmembrane α‑helices and a large internal loop that houses regulatory motifs.

The kinetic properties of Can1p resemble typical facilitated diffusion: it has a high affinity for arginine with a Km in the micromolar range and a maximum transport rate (Vmax) that is dependent on the cell cycle stage. Transport activity is electrogenic, driven by the membrane potential and modulated by intracellular pH. In addition to direct transport, Can1p participates in a transceptor signaling pathway that triggers the arrest of growth and the activation of arginine catabolic genes under conditions of amino acid excess.

Can1p expression is tightly regulated at multiple levels. Transcription is induced by low intracellular amino acid concentrations and repressed by arginine and other cognate substrates through a feedback loop involving the transcription factor Stp1. Post‑transcriptional control occurs via ubiquitination of the N‑terminal tail, which targets the protein for endocytosis and vacuolar degradation. The protein is also subject to post‑translational modifications, including N‑glycosylation in the extracellular loops that influence stability and localization.

Genetic mutations in CAN1 result in loss-of-function phenotypes that confer resistance to the arginine analogs canavanine and thialysine, a property that is exploited in selectable marker systems. The Can1p protein has been extensively used as a model for studying membrane transport, protein trafficking, and the interplay between nutrient sensing and cell growth.