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Introduction
Biological Introduction
SHOC2-PP1C-MRAS is a human enzyme that is involved in regulating cell proliferation and division[1]. The enzyme is involved in the vast RAS-MAPK pathway, which is initially activated by an extracellular growth factor binding to a membrane bound RAS GTPase[1] such as HRAS, NRAS, or KRAS. RAS-GTPases are a family of proteins that work by functioning as molecular switches[2]. This occurs from the protein alternating between binding GTP to be active and GDP to be inactive [1]. After activation via an extracellular growth factor, the RAS-GTPase enzyme binds GTP, which activates RAF[2].
Structural Introduction
The enzyme requires 3 domains (SHOC-2(blue), PP1C(coral), and MRAS (green)) to form the active enzyme (SMP Complex), also known as a [3]. SHOC-2 is a scaffolding protein that holds the other subunits in the correct orientation, allowing for the holoenzyme to be functional. PP1C is a catalytic domain of a phosphatase enzyme PP1[3], which cleaves ____. MRAS is a GTPase protein and is located near (typically just below) the cell membrane. When MRAS binds GTP, it becomes active and triggers the assembly of the active holoenzyme[3]. The SMP complex was determined via cryo-electron microscopy as well as x-ray diffraction. These studies found that PP1C and MRAS occupy the concave surface of SHOC2, leaving the catalytic site of PP1C and the substrate binding cleft in MRAS exposed.
Sources
Liau [4]
Hauseman[3]
Kwon [5]
Lavoie [6]
Abstract LB029[7]
Bonsor[8]
Young(MRAS section) [9]
Kwon and Hahn (SHOC2 section) [10]
PP1C section external link
blue link LRR LRR
Arkun (for ERK signaling) [11]
For last sentence in implications van der Burgt [12]
PP1C REF: [13].
Relevance
Structural highlights
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