Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein mio and simialr proteins
This family contains Mio,its counterpart Sea4 from yeast, and other homologs. Mio/Sea4 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Sea3/WDR59. 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. Mio interacts with endogenous RagA and RagC, and plays an essential role in the activation of mTOR Complex 1 (mTORC1) by amino acids. In GATOR2, Mio and Seh1 localize to lysosomes and autolysosomes, and form a heterodimer that is required to oppose the TORC1 inhibitory activity of the Iml1/GATOR1 complex to prevent the constitutive down-regulation of TORC1 activity in later stages of oogenesis. A tissue-specific requirement is necessary for Mio to be involved in cell growth in the female germ line. Mio contains an N-terminal WD40 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.
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 Mio 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 4 residues rather than the usual 2 residues.
Jiyao W et al.(2023). "The conserved domain database in 2023.",