The name "SHOC2" was given because of the homology (or resemblance) to a C. elegans protein called Suppressor Of Clr protein-2 (SOC-2 or sometimes SUR-8).

SHOC2 is a Leucine rich repeat (LRR) scaffold protein in Homo sapiens, it is encoded by the Shoc2 gene located on the q arm of chromosome 10 (10q25). A scaffold protein by definition, SHOC2 has the simple but impotent job of holding other proteins together and facilitating their interaction. In the case of SHOC2, these two target proteins happen to be part of a very crucial pathway known as the Ras Signaling and MAP Kinase activation pathway. Due to the importance of this pathway in development, a mutation in SHOC2 was found to be responsible to Noonan Syndrome-Like with Loss of Anagen Hair (NSLAH), which is a multi-symptomatic disorder that shortens the stature, effects facial features and many organs, such as the brain, skin, muscles and especially the hart.

The molecular role of SHOC2. Ras is a G protein, a protein that binds Guanine phosphate, when Ras is inactive it is bound to guanine di-phosphate (GDP). The G protein is activated only after GDP is exchanged for GTP (tri-phosphate). Ras is activated by a GDP to GTP Exchange Factor (GEF), mostly Growth Factor Receptors. SHOC2 binds activated Ras in the cytosol of the cell and then binds another protein called Raf, this facilitates the interaction of Ras and Raf, the Phospho-transfer of the Raf-phosphate to another protein downstream and the consequent activation of the MAP Kinase pathway that targets gene expression.

Noonan Syndrome-Like with Loss of Anagen Hair (NSLAH) is a type of Noonan Syndrome caused by a mutation in the Shoc2 gene. The discovery of this mutation was the first time when an aberrant post-translational modification ,such as Miristoylation, was found to cause disease in humans. The missense mutation in exon 2 of the gene, changes the codon for the amino acid Serine to that of Glycine and forms a new N-Miristoylation site. Because of this modification, SHOC2 is targeted to the membrane instead of the cytoplasm and can not facilitate Ras and Raf interaction as favorably. NSLAH is a multi-symptomatic disorder that shortens the stature, effects facial features and many organs, such as the brain, skin, muscles and especially the hart. [1]

High impact information on SHOC2

• SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans [2].
• Furthermore, in tumor cells with Ras gene mutations, inhibition of Shoc2 expression inhibits MAPK, but not PI3K activity [3].
• A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity [3].
• Using a proteomics approach, we have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector [3].
• Within the leucine-rich repeats of both SOC-2 and SHOC-2 are two YXNX motifs that are potential tyrosine-phosphorylated docking sites for the SEM-5/GRB2 Src homology 2 domain [4].

Biological context of SHOC2

• However, phosphorylation of these residues is not required for SOC-2 function in vivo, and SHOC-2 is not observed to be tyrosine phosphorylated in response to FGF stimulation [4].

Anatomical context of SHOC2

• This property is specific to the LRR domain of LAP proteins, as the non-LAP protein SUR-8 does not localize at the basolateral membrane of epithelial cells, despite having a closely related LRR domain [5].

References