RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING finger protein MARCH1, MARCH8, and similar proteins
This subfamily includes the closely related MARCH1 and MARCH8, both of which are located on endosomes and the plasma membrane and are implicated in regulating cell surface expression of their substrates. They ubiquitylate and downregulate many targets, including major histocompatibility complex class II (MHCII), CD86, transferrin receptor, HLA-DM, and Fas from the cell surface. MARCH1 is mainly expressed in cells of the immune system, while MARCH8 is more broadly expressed. Both of them contain an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and two transmembrane domains. The cytoplasmic RING-CH finger participates in the ubiquitin transfer from the E2 to its substrate. The transmembrane domains are implicated in target recognition and dimer formation.
Structure:2D8S; Homo sapiens MARCH8 binds two Zn2+ ions through its RING-CH finger.
Comment:RING-CH finger (C4HC3-type)
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 MARCH proteins 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 in the sequence as C4HC3-type, rather than the typical C3H2C3-type in RING-H2 finger.
Jiyao W et al.(2023). "The conserved domain database in 2023.",