Leucine-rich repeat A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats common ...

(LRR) protein SHOC-2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that in humans is encoded by the ''SHOC2''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The best-studied role of SHOC2 is in modulating signals of the extracellular signal-regulated kinase 1 and 2 ( ERK1/2) pathway by forming a holophosphatase complex that activates RAF proteins(). This protein was initially identified in ''Caenorhabditis elegans'' as SUR-8/SOC2 and was found to be a critical positive regulator of the ERK1/2 signaling pathway that integrates the Ras and RAF components of the ERK1/2 pathway into a multiprotein complex. Specifically, SHOC2 tethers RAS and PP1C proteins and in close proximity to RAF to dephosphorylate “S259” to enable MAPK signaling. It has been shown that activity that results in lipidation (specifically

Myristoylation Myristoylation is a lipidation modification where a myristoyl group, derived from myristic acid, is covalently attached by an amide bond to the alpha-amino group of an N-terminal glycine residue. Myristic acid is a 14-carbon saturated fatty aci ...

) of SHOC2 can cause

Noonan syndrome Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored ...

Interactions

SHOC2 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...

with the catalytic phosphatase subunit PP1C() and MRAS as well as canonical RAS isoforms (H/K/NRAS)(). The ternary complex SHOC2-RAS-PP1C functions to dephosphorylate an inhibitory phosphorylation site ('S259') on RAF family proteins to enable MAPK signaling().

SHOC2 Dependent Dynamic Regulation of MAPK signaling

The amplitude of SHOC2-mediated ERK1/2 signals has been proposed to be regulated by differential regulation of RAF activation at the plasma membrane and internalized endosome compartment () as well an alternative model proposing post-translational modifications(). SHOC2

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. F ...

ation mediated by

HUWE1 E3 ubiquitin-protein ligase HUWE1 is an enzyme that in humans is encoded by the ''HUWE1'' gene. It performs the third step (ligation) in binding ubiquitin to proteins in a process called ubiquitination which tags the proteins for disposal. Human ...

is triggered by growth factor activation of the ERK1/2 pathway and is a prerequisite for the subsequent ubiquitination of the RAF-1 kinase associated with SHOC2. However, the current data has yet to address how these ubiquitin modifications regulate the SHOC2 holophosphatase function to reduce the amplitude of RAF-ERK1/2 signals.

Interactions

SHOC2 Dependent Dynamic Regulation of MAPK signaling

References

Further reading