Recombinant Human Ras-related protein M-Ras (MRAS)

Function

Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (PubMed:16630891, PubMed:28289718, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The formation of the SMP complex only occurs when MRAS is GTP-bound (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39809765). Unlike other Ras proteins, MRAS has low intrinsic GTPase activity and may require additional factors for activation (PubMed:39809765). 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:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (PubMed:40934300)

Subcellular Location

Cell membrane (Lipid-anchor)

Disease Association

Noonan syndrome 11 (NS11) : A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS11 inheritance is autosomal dominant. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expression highly restricted to the brain and heart

Subunit

Component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex consisting of SHOC2, GTP-bound M-Ras/MRAS and the catalytic subunit of protein phosphatase 1 (either PPP1CA, PPP1CB or PPP1CC) (PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39809765). Interacts (active GTP-bound form) with both SHOC2 and PP1c (all isoforms) to form a tertiary complex; SHOC2 and PP1c preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39809765). Interacts with RGL3 (By similarity). Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (GDP-bound form) with LZTR1; this interaction mediates MRAS ubiquitination by BCR E3 ligase complex (PubMed:40934300)

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• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• Rodriguez-Viciana P. et al. A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity. — Mol. Cell (2006)