{PDOC51872}
{PS51872; ZF_ZBR}
{BEGIN}
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* Zinc finger ZBR-type profile *
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The post-translational  modification of proteins by the covalent attachment of
ubiquitin (ubiquitylation) regulates various cellular processes of eukaryotes.
The ubiquitylation reaction is catalyzed by a set of three enzymes: ubiquitin-
activating enzyme, E1; ubiquitin-conjugating enzyme, E2; and ubiquitin ligase,
E3. The  anaphase-promoting  complex or cyclosome (APC/C) is a multisubunit E3
ligase enzyme  that  regulates  cell  division  by promoting timely ubiquitin-
mediated proteolysis  of  key cell-cycle regulatory proteins. Emi1/Fbx5 (early
mitotic inhibitor  1;  gene  symbol,  FBX05)  and  Emi2/Erp1/Fbx43 (endogenous
meiotic inhibitor 2 or Emi1-related protein 1; gene symbol, FBX043) constitute
the Emi/Erp  protein  family  of  APC/C inhibitors against the APC/C function,
which controls  cell  division  progress.  Emi1  and Emi2 share the F-box (see
<PDOC50181>) and DB motifs, the zinc-binding region (ZBR) with the in-between-
RING (IBR)  topology  and the C6HC-type zinc-binding motif, and the C-terminal
region with  a conserved 14-residue sequence ending in the RL residues, termed
the RL tail [1,2,3].

The ZBR-type  zinc  finger  is  an  autonomously folded domain with a central,
twisted, four-stranded  beta-sheet  and  two zinc ions on opposite ends of the
sheet (see  <PDB:2M6N>).  One  zinc  is chelated by the beta1-beta2 and beta3-
beta4 loops and the other by the beta2-beta3 loop and a loop following beta 4.
The ZBR finger displays an In-Between-RING (IBR) domain topology [1,2,3].

The profile we developed covers the entire ZBR-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: August 2018 / First entry.

[ 1] Shoji S., Muto Y., Ikeda M., He F., Tsuda K., Ohsawa N., Akasaka R.,
     Terada T., Wakiyama M., Shirouzu M., Yokoyama S.
     "The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by
     targeting its association with the coactivator Cdc20 and
     UBE2C-mediated ubiquitylation."
     FEBS Open Bio 4:689-703(2014).
     PubMed=25161877; DOI=10.1016/j.fob.2014.06.010
[ 2] Frye J.J., Brown N.G., Petzold G., Watson E.R., Grace C.R.R., Nourse A.,
     Jarvis M.A., Kriwacki R.W., Peters J.-M., Stark H., Schulman B.A.
     "Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals
     multimodal mechanism of E3 ligase shutdown."
     Nat. Struct. Mol. Biol. 20:827-835(2013).
     PubMed=23708605; DOI=10.1038/nsmb.2593
[ 3] Chang L., Zhang Z., Yang J., McLaughlin S.H., Barford D.
     "Atomic structure of the APC/C and its mechanism of protein
     ubiquitination."
     Nature 522:450-454(2015).
     PubMed=26083744; DOI=10.1038/nature14471

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