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H-ras proto-oncogene protein (Harvey ras, p21Hras, Ha-ras)
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
a) Costello syndrome
b) bladder cancer
c) 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
Interactions
molecular events
Related
H-ras proto-oncogene
General
ras proto-oncogene protein (p21ras)
Properties
SIZE: entity length = 189 aa
MW = 21 kD
COMPARTMENT: cytoplasm
golgi
MOTIF: GTP-binding site
SITE: 10-17
Effector region {32-40}
GTP-binding site
SITE: 57-61
GTP-binding site
SITE: 116-119
Hypervariable region {166-185}
MOTIF: cysteine residue {C181}
MODIFICATION: palmitate
COMPARTMENT: membrane
cysteine residue {C184}
MODIFICATION: palmitate
COMPARTMENT: membrane
CaaX motif
SITE: C-TERMINUS
QUALITIES: AAX-TRUNCATED
CARBOXYMETHYLATED
EFFECTOR-BOUND: farnesyl
BOUND-VIA: cysteine residue
Database Correlations
OMIM correlations
MORBIDMAP 190020
UniProt P01112
Pfam PF00071
Kegg hsa:3265
References
- Boguski MS & McCormick F
Proteins regulating Ras and its relative.
Nature 366:643 1993
PMID: 8259209
- UniProt :accession P01112
- Atlas of genetics & cytogenetics in oncology & haematology
http://atlasgeneticsoncology.org/genes/HRASID108.html
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=HRAS