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PROSITE documentation PDOC51981

Zinc finger RZ-type profile





Description

The RNF213–ZNFX1 (RZ)-type zinc finger is found in:

  • RNF213, a giant E3 ubiquitin ligase and a major susceptibility factor of Moyamoya disease, a cerebrovascular disorder that can result in stroke or death. In the cell, RNF213 is involved in lipid droplet formation, lipotoxicity, hypoxia, and NF-kappaB signaling. RNF213 restricts the proliferation of cytosolic Salmonella and is essential for the generation of the bacterial ubiquitin coat, both directly (through the ubiquitylation of lipopolysaccharide (LPS)) and indirectly (through the recruitment of LUBAC, which is a downstream E3 ligase that adds M1-linked ubiquitin chains onto pre-existing ubiquitin coats). RNF213 comprises an N-terminal stalk, a dynein-like core with two catalytically active and four inactive AAA+ (ATPases Associated with diverse cellular Activities) domains, and a multidomain E3 module that surrounds a RING domain.
  • NFX1-type zinc finger containing protein (ZNFX1), an interferon-induced RNA helicase that has antiviral function.

The ubiquitylation of LPS on Salmonella that invade the cytosol relies on the RZ-type zinc finger in the E3 module of RNF213 [1].

The RZ-type zinc finger contains two conserved histidine residues and four conserved cysteine residues in a CHC3H motif. It can bind divalent transition metals, with a preference for Zn(2+). Residues C1, H1, C3, and C4 coordinate the metal ion, whereas C2, not involved in zinc coordination, is the catalytic cysteine nucleophile involved in E2-E3 transthiolation. H2 is located on a flexible loop region adjacent to the loop carrying the active site C2 and might act as a general base that deprotonates the substrate nucleophile [2].

The profile we developed covers the entire RZ-type zinc finger.

Last update:

July 2021 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

ZF_RZ, PS51981; Zinc finger RZ-type profile  (MATRIX)


References

1AuthorsOtten E.G. Werner E. Crespillo-Casado A. Boyle K.B. Dharamdasani V. Pathe C. Santhanam B. Randow F.
TitleUbiquitylation of lipopolysaccharide by RNF213 during bacterial infection.
SourceNature 594:111-116(2021).
PubMed ID34012115
DOI10.1038/s41586-021-03566-4

2AuthorsAhel J. Fletcher A. Grabarczyk D.B. Roitinger E. Deszcz L. Lehner A. Virdee S. Clausen T.
TitleE3 ubiquitin ligase RNF213 employs a non-canonical zinc finger active site and is allosterically regulated by ATP.
SourcebioRxiv 0:0-0(2021).
DOI10.1101/2021.05.10.443411



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