9.B.423.1.2
5,6-dihydroxyindole-2-carboxylic acid oxidase (TYRP1, TYR, CAS2, TYRP, TYRRP) of 537 aas and 2 TMSs, one signal sequence at the N-terminus and one very hydrophobic TMS at the C-terminus.  It plays a role in melanin biosynthesis (Kenny et al. 2012, Rooryck et al. 2006) and catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu²⁺ ions, but not in the presence of Zn²⁺ (Lai et al. 2017).  Tyrosinase is a key enzyme in the process of melanin synthesis that occurs exclusively within specialized organelles called melanosomes in melanocytes. Tyr is synthesized and post-translationally modified independently of the formation of melanosome precursors and then transported to immature melanosomes by a series of membrane trafficking events that includes endoplasmic reticulum (ER)-to-Golgi transport, post-Golgi trafficking, and endosomal transport (Nakamura and Fukuda 2024). Several regulators of Tyr transport have been identified. Tyr is present in several melanocyte organelles under steady-state conditions, thereby precluding the possibility of determining where Tyr is being transported at any given moment. Nakamura and Fukuda 2024 established a novel synchronized Tyr transport system in Tyr-knockout B16-F1 cells by using Tyr tagged with an artificial oligomerization domain FM4 (named Tyr-EGFP-FM4). Tyr-EGFP-FM4 was initially trapped at the ER under oligomerized conditions, but at 30 min after chemical dissociation into monomers, it was transported to the Golgi, and at 9 h, it reached immature melanosomes. Melanin was then detected at 12 h after the ER exit of Tyr-EGFP-FM4. By using this synchronized Tyr transport system, the authors were able to show that Tyr-related protein 1 (Tyrp1), another melanogenic enzyme, is a positive regulator of efficient Tyr targeting to immature melanosomes.