{PDOC51981}
{PS51981; ZF_RZ}
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* Zinc finger RZ-type profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2021 / First entry.

[ 1] Otten E.G., Werner E., Crespillo-Casado A., Boyle K.B.,
     Dharamdasani V., Pathe C., Santhanam B., Randow F.
     "Ubiquitylation of lipopolysaccharide by RNF213 during bacterial
     infection."
     Nature 594:111-116(2021).
     PubMed=34012115; DOI=10.1038/s41586-021-03566-4
[ 2] Ahel J., Fletcher A., Grabarczyk D.B., Roitinger E., Deszcz L.,
     Lehner A., Virdee S., Clausen T.
     "E3 ubiquitin ligase RNF213 employs a non-canonical zinc finger active
     site and is allosterically regulated by ATP."
     bioRxiv 0:0-0(2021).
     DOI=10.1101/2021.05.10.443411

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