SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex

Stable Identifier
R-HSA-9660536
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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SHOC2 M173I disrupts the SHOC2:MRAS:PP1 complex
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A loss-of-function mutation in SHOC2 has been identified in a patient with a Noonan-related syndrome (Hannig et al, 2014). SHOC2 M173I has impaired ability to interact with PPP1CC and reduces the MRAS-SHOC2-PP1-dependent dephosphorylation of RAF, which is required for RAF pathway activation (Rodriguez-Viciano et al, 2006; Hannig et al, 2014). How both loss and gain-of-function SHOC2 mutants can contribute to RAF pathway activation remains to be elucidated.
Literature References
PubMed ID Title Journal Year
25137548 A Novel SHOC2 Variant in Rasopathy

Hannig, V, Galperin, E, Phillips, JA, Jeoung, M, Jang, ER

Hum. Mutat. 2014
16630891 A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity

McCormick, F, Fried, M, Burlingame, A, Oses-Prieto, J, Rodriguez-Viciana, P

Mol. Cell 2006
Participants
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Catalyst Activity

protein serine/threonine phosphatase activity of SHOC2 M173I:MRAS:PP1 [plasma membrane]

Physical Entity
SHOC2 M173I:MRAS:PP1 [plasma membrane] (Homo sapiens)
Activity
protein serine/threonine phosphatase activity (GO:0004722)
Normal reaction
MRAS:SHOC2:PPP1CC dephosphorylates inactive RAFs (Homo sapiens)
Functional status

Loss of function of SHOC2 M173I:MRAS:PP1 [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
Noonan syndrome DOID:3490 Turner's phenotype, karyotype normal (disorder)
Authored
Rothfels, K  (2019-10-25)
Reviewed
Gavathiotis, E  (2020-05-04)
Created
Rothfels, K  (2019-09-09)
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