My note on RNF43 protein domains -- ring finger transmembrane protein

It is the note that I have skimmed from three different papers.

1. ZNRF3/RNF43--A direct linkage of extracellular recognition and E3 ligase activity to modulate cell surface signaling (doi:10.1016/j.pbiomolbio.2015.04.006) -- 2015

2. The structural basis of R-spondin recognition by LGR5 and RNF43 (doi:10.1101/gad.219915.113) -- 2013

3.The Role of the Transmembrane RING Finger Proteins in Cellular and Organelle Function (doi:10.3390/membranes1040354) -- 2011

RNF43 controls the abundance of Fz on the cell membrane.

RNF43 is E3 ubiquitin ligase which adds Ub to the target molecule.

RNF43 have three different domain; PA (ectodomain)-TM-RING (internal domain)

Common feature of TM-E3 ligase -- self-ubiquitination, therefore, it remains low ubiquitination of targeted protein, like for RNF43 is Fz, for example --> interfering of self-ubiquitination --> afftect the abundance of E3-ligase's targeted protein. 

RNF43 is paralogous to ZNRF3 but structural analysis, ZNRF3 tents to form oligomer (2:2:2 - ZNRF3:Rspondin:LGR5) whereas RNF43 is able to be monomer complex (1:1:1).

Both RNF43 and ZNRF3 -- Goliath and Godzilla family.

RNF43-PA domain share "structural similarity" with GRAIL/RNF128 -- evolutionarily conserved architecture. 

RNF43 becomes hot since 2012 when it was found that it controls the wnt signaling --> related to the cancer besides the normal roles in embryogenesis, stem cell, cell differentiation--> some cancers are driven by wnt.

Because of its domain; RNF43 can be found at cell membrane, nucleus membrane and some reported it could be found in the nucleoplasm-but very little (kind of wondering though since it has TM - how this protein appears in the nucleoplasm -- as the vesicle?)

This picture shows how RNF43 control the dynamic of Fz receptor and degradation of RNF43 leading to the abundance of Fz receptor on the cell membrane.

Amino acid alignment of PA domain. Pink hexagon is N-glycosylation sites, full-circle is ligand binding sites and triangle refers to ZNRF3 dimerization interaction.

I love this table because it summarized the functions of TM RNF proteins; see below how many forms of TM RNFs.

Just waiting for the era of machine learning; very soon it could predict the unk binding partners.

Technical note to prevent aggregation of some proteins that I have learned from;

LGR5 is expressed together with RSPO1 -- to prevent the aggregation of LGR5 when expressing alone.