Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein 59 (WDR59) and similar proteins
WDR59 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Mio/Sea4. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. WDR59 contains an N-terminal WD40 domain followed by a RWD domain, and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type. Sea3 is the yeast counterpart of WDR59. It is not included in this subfamily.
Comment:C3H2C3-type RING-H2 finger consensus motif: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, where X is any amino acid and the number of X residues varies in different fingers
Comment:A RING finger typically binds two zinc atoms, with its Cys and/or His side chains in a unique "cross-brace" arrangement.
Comment:The RING fingers found in WDR59 and its homologs have an unusual arrangement of zinc-coordinating residues: The conserved helix complete with tryptophan at the C-terminal end is present but the cysteines and histidines are arranged as C3H3C2-type, rather than the typical C3H2C3-type, and the spacing between the fourth and fifth cysteines is an extended 3 residues rather than the usual 2 residues.
Jiyao W et al.(2023). "The conserved domain database in 2023.",