| Structural highlights
Disease
RASN_HUMAN Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:613224. A syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.[1] Defects in NRAS are the cause of autoimmune lymphoproliferative syndrome type 4 (ALPS4) [MIM:614470. A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.[2]
Function
RASN_HUMAN Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
Publication Abstract from PubMed
It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix-turn-coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.
Structural characterization of NRAS isoform 5.,Markowitz J, Mal TK, Yuan C, Courtney NB, Patel M, Stiff AR, Blachly J, Walker C, Eisfeld AK, de la Chapelle A, Carson WE 3rd Protein Sci. 2016 May;25(5):1069-74. doi: 10.1002/pro.2916. Epub 2016 Mar 24. PMID:26947772[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D, Roberts AE, Lepri F, Merbitz-Zahradnik T, Konig R, Kratz CP, Pantaleoni F, Dentici ML, Joshi VA, Kucherlapati RS, Mazzanti L, Mundlos S, Patton MA, Silengo MC, Rossi C, Zampino G, Digilio C, Stuppia L, Seemanova E, Pennacchio LA, Gelb BD, Dallapiccola B, Wittinghofer A, Ahmadian MR, Tartaglia M, Zenker M. A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet. 2010 Jan;42(1):27-9. Epub 2009 Dec 6. PMID:19966803 doi:10.1038/ng.497
- ↑ Oliveira JB, Bidere N, Niemela JE, Zheng L, Sakai K, Nix CP, Danner RL, Barb J, Munson PJ, Puck JM, Dale J, Straus SE, Fleisher TA, Lenardo MJ. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8953-8. Epub 2007 May 16. PMID:17517660 doi:10.1073/pnas.0702975104
- ↑ Markowitz J, Mal TK, Yuan C, Courtney NB, Patel M, Stiff AR, Blachly J, Walker C, Eisfeld AK, de la Chapelle A, Carson WE 3rd. Structural characterization of NRAS isoform 5. Protein Sci. 2016 May;25(5):1069-74. doi: 10.1002/pro.2916. Epub 2016 Mar 24. PMID:26947772 doi:http://dx.doi.org/10.1002/pro.2916
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