CTLH complex subunits
ctlh complex subunits
The C-terminal to LisH (CTLH) complex (called the glucose-induced degradation deficient (GID) complex in yeast), is a multi-subunit E3 ligase complex highly conserved from Saccharomyces cerevisiae to humans, with roles in fundamental pathways controlling homeostasis and development in several species. The CTLH complex is characterized by its RING heterodimer, multiple protein interaction domains, and LisH, CTLH, and CRA motifs present on most protein subunits. In humans, RANBP9 (homolog of Gid1), GID8 and ARMC8 (similar to Gid5) act as a scaffold; RMND5A (homolog of Gid2) and MAEA (homolog of Gid9) are the RING heterodimers required for E3 ligase activity; and GID4 (homolog of Gid4) acts a substrate receptor (WDR26, homologue of Gid7, may also act in this role). WDR26 and/or MKLN1 bind RANBP9 and facilitate oligomerization of the complex. Additionally, paralogues of RMND5A and RANBP9, RMND5B and RANBP10 have been implied as human complex members so are included here. Human YPEL5 and its orthologs (Moh1 in yeast) are also part of the complex, but their role is unclear. Key to the activity of the complex, RMND5A/Gid2 and MAEA/Gid9 provide a unique RING domain heterodimer that can bind the E2 enzyme UBE2H (Ubc8 in S. cerevisiae) and stimulate E2-catalyzed Ub transfer to a recruited substrate.