Related Experiment Video

Updated: Aug 22, 2026

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay
13:51

Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay

Published on: November 11, 2018

Human RAS superfamily proteins and related GTPases

John Colicelli1

  • 1Department of Biological Chemistry and Molecular Biology Institute, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. colicelli@mednet.ucla.edu <colicelli@mednet.ucla.edu>

Science'S STKE : Signal Transduction Knowledge Environment
|September 16, 2004
PubMed

Insights

The RAS superfamily, including HRAS, KRAS, and NRAS, comprises over 170 human proteins. This study guides functional prediction for these GTP-binding signaling proteins and related GTPases.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • The RAS superfamily includes key tumor oncoproteins like HRAS, KRAS, and NRAS.
  • This superfamily encompasses over 170 related human proteins involved in signal transduction.
  • RAS proteins function as guanosine triphosphate (GTP) hydrolysis-coupled signal relays.

Purpose of the Study:

  • To classify the extensive RAS superfamily and related GTPases.
  • To provide a framework for predicting the functions of uncharacterized members.
  • To highlight the structural and functional diversity within the RAS superfamily.

Main Methods:

  • Sequence similarity analysis to define the RAS superfamily.
  • Subclassification into RAS, RHO, RAB, ARF, and Galpha families.
  • Analysis of evolutionary conservation and functional characteristics.

Main Results:

  • Identified over 170 RAS-related proteins, extending beyond known oncoproteins.
  • Established subfamilies (RAS, RHO, RAB, ARF, Galpha) and conserved branches.
  • Characterized signaling properties of representative members, aiding functional prediction.

Conclusions:

  • The RAS superfamily is vast and structurally diverse, playing critical roles in cellular signaling.
  • This classification aids in understanding the function of numerous uncharacterized RAS-related proteins.
  • Related GTPases with diverse structures expand the functional scope beyond the canonical RAS superfamily.

More Related Videos

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve09:13

Optimized Protocol for the Extraction of Proteins from the Human Mitral Valve

Published on: June 14, 2017

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry09:38

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

Published on: June 26, 2019

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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.
Three regulatory proteins control their activity:
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
The Ras Gene02:38

The Ras Gene

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 superfamily...
Rab Proteins01:14

Rab Proteins

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...