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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Rab Proteins01:14

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Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
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Small GTPases - Ras and Rho01:24

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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Rab Cascades01:25

Rab Cascades

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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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Insertion of Single-pass Transmembrane Proteins in the RER01:26

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Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
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Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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Origin and Evolution of RAS Membrane Targeting.

Antonio García-España1, Mark R Philips2

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Summary
This summary is machine-generated.

The study traces the evolutionary history of RAS proto-oncogenes, revealing KRAS as the ancestral gene. Gene duplications led to HRAS, NRAS, and KRASBL, with specific exon reshuffling creating KRAS4A.

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Area of Science:

  • Evolutionary biology
  • Molecular genetics
  • Cellular signaling

Background:

  • RAS proto-oncogenes (KRAS, HRAS, NRAS) are critical regulators of cell signaling.
  • Their evolutionary origins and the functional significance of their isoforms remain largely unexplored.
  • RAS proteins feature a G-domain and a hypervariable region (HVR) for membrane association.

Purpose of the Study:

  • To investigate the evolutionary history of RAS isoforms and their hypervariable regions.
  • To understand the molecular mechanisms driving RAS gene diversification.
  • To explore the functional implications of evolutionary changes in RAS proteins.

Main Methods:

  • Phylogenetic analysis of RAS gene family evolution.
  • Comparative genomics to identify gene duplication and exon shuffling events.
  • Bioinformatic analysis of conserved protein domains and motifs.

Main Results:

  • KRAS is identified as the basal RAS proto-oncogene, with HRAS arising from its duplication.
  • Subsequent duplications generated NRAS and KRASBL, while KRAS4A resulted from exon duplication and insertion.
  • Conserved regions (PBR1, PBR2, NB) and modified C-terminal motifs suggest adaptation to specific membrane anchors.

Conclusions:

  • The evolutionary trajectory of RAS genes highlights a complex history of duplication and rearrangement.
  • Conserved structural features across RAS isoforms suggest critical, conserved functions.
  • Divergence in membrane anchoring mechanisms points to specialized roles for different RAS proteins.