HRAS
Function
Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151).
Involvement in disease
Costello syndrome
CSTLO
A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.
None
The disease is caused by variants affecting the gene represented in this entry.
Congenital myopathy with excess of muscle spindles
CMEMS
Variant of Costello syndrome.
None
The disease is caused by variants affecting the gene represented in this entry.
Thyroid cancer, non-medullary, 2
NMTC2
A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.
Bladder cancer
BLC
A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Schimmelpenning-Feuerstein-Mims syndrome
SFM
A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.
S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation.
The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.
Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).
Fatty-acylated at Lys-170.
Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes.
(Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin TcsL (PubMed:19744486, PubMed:8626575, PubMed:8626586, PubMed:9632667). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to inhibit Ras signaling (PubMed:8626575, PubMed:8626586, PubMed:9632667).
Sequence Similarities
Belongs to the small GTPase superfamily. Ras family.
Tissue Specificity
Widely expressed.
Cellular localization
- Cell membrane
- Lipid-anchor
- Cytoplasmic side
- Golgi apparatus
- Golgi apparatus membrane
- Lipid-anchor
- The active GTP-bound form is localized most strongly to membranes than the inactive GDP-bound form (By similarity). Shuttles between the plasma membrane and the Golgi apparatus.
- Isoform 2
- Nucleus
- Cytoplasm
- Cytoplasm
- Perinuclear region
- Colocalizes with RACK1 to the perinuclear region.
Alternative names
HRAS1, HRAS, GTPase HRas, H-Ras-1, Ha-Ras, Transforming protein p21, c-H-ras, p21ras