RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH6 (MARCH6)
MARCH6, also known as membrane-associated RING finger protein 6, membrane-associated RING-CH protein VI (MARCH-VI), RING finger protein 176 (RNF176), protein TEB-4, or Doa10 homolog, is an endoplasmic reticulum (ER)-localized E3 ubiquitin ligase that ubiquitinates ER-associated proteins with a cytoplasmic domain in a ubiquitin-conjugating enzyme 7 (UBC7)-dependent manner), such as Mps2, UBC6, and Ste6. It also regulates its own UBC7-mediated degradation. MARCH6 interacts with ubiquitin-specific protease USP19, which deubiquitinates and stabilizes MARCH6 and inhibits p97-dependent proteasomal degradation. It is also involved in the cholesterol synthesis pathway by controlling the degradation of squalene monooxygenase (SM), and affects 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). Furthermore, it may be a key regulator of thyroid hormone activation in a number of tissues, since it mediates the proteasomal degradation of type 2 iodothyronine deiodinase (D2). MARCH6 contains 14 transmembrane helices and a conserved N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, that catalyzes ubiquitin Lys48-specific ligation.
Structure:2M6M; Saccharomyces cerevisiae Doa10p 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.",