H-ras proto-oncogene protein (Harvey ras, p21Hras, Ha-ras)

Introduction

Harvey ras. One of 4 'true' ras proteins [p21ras].

Function

• Ras proteins bind GDP/GTP & possess intrinsic GTPase activity
• in its GTP-bound form interacts with PLCE1
• interacts with TBC1D10C.
• interacts with RGL3 (putative)
• forms a signaling complex with RASGRP1 & DGKZ
• alternates between an inactive form bound to GDP & an active form bound to GTP
• activated by a guanine nucleotide-exchange factor (GEF)
• inactivated by a GTPase-activating protein (GAP)
• palmitoylated by the ZDHHC9-GOLGA7 complex
• a continuous cycle of de- & re-palmitoylation regulates rapid exchange between plasma membrane & Golgi
• p21ras binds to & activates raf1 protein probably in association with other proteins; raf1 activates MEK which in turn activates MAP kinases

Structure

belongs to the small GTPase superfamily, Ras family

Compartment

• cell membrane, lipid-anchor, cytoplasmic side
• Golgi membrane, lipid-anchor
• shuttles between the plasma membrane & the Golgi apparatus

Pathology

• defects in HRAS are the cause of
  • Costello syndrome
  • bladder cancer
  • oral squamous cell carcinoma
    • mutations which change positions 12, 13 or 61 activate the potential of c-ras to transform cultured cells & are implicated in a variety of human tumors

More general terms

• ras proto-oncogene protein (p21ras)

Database

• UniProt: http://www.uniprot.org/uniprot/P01112.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3265
• OMIM: https://mirror.omim.org/entry/109800
• OMIM: https://mirror.omim.org/entry/190020
• OMIM: https://mirror.omim.org/entry/218040