SHOC2
Domain
Contains a N-terminal RVxF motif that is important for interaction with PP1c.
PP1c (all isoforms) binds to the concave side of SHOC2, via LRR 2-5, 8-11, and 13-18 (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). M-Ras/MRAS binds to the concave side of SHOC2, via LRR 1-10, 12 and 14-16 (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670).
Function
Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway (PubMed:10783161, PubMed:16630891, PubMed:25137548, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Acts as a scaffolding protein in the SMP complex (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:10783161, PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670).
Involvement in disease
Noonan syndrome-like disorder with loose anagen hair 1
NSLH1
A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the SHOC2 family.
Cellular localization
- Cytoplasm
- Nucleus
- Translocates from cytoplasm to nucleus upon growth factor stimulation.
Alternative names
KIAA0862, SHOC2, Leucine-rich repeat protein SHOC-2, Protein soc-2 homolog, Protein sur-8 homolog