scholarly journals Identification and Functional Characterization of Novel Mutations in the Melanocortin-4 Receptor

Obesity Facts ◽  
2010 ◽  
Vol 3 (5) ◽  
pp. 304-311 ◽  
Author(s):  
Sigri Beckers ◽  
Doreen Zegers ◽  
Fenna de Freitas ◽  
Armand V. Peeters ◽  
Stijn L. Verhulst ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Novel Mutations ◽  
Melanocortin 4 Receptor

Functional characterization of a new human melanocortin-4 receptor homozygous mutation (N72K) that is associated with early-onset obesity

2014 ◽  
Vol 41 (12) ◽  
pp. 7967-7972 ◽  
Author(s):  
Patric J. D. Delhanty ◽  
Elise Bouw ◽  
Martin Huisman ◽  
Resie M. L. Vervenne ◽  
Axel P. N. Themmen ◽  
...  
Keyword(s):  
Early Onset ◽  
Functional Characterization ◽  
Homozygous Mutation ◽  
Melanocortin 4 Receptor

scholarly journals Functional characterization of novel mutations in the human cytochrome b gene

2001 ◽  
Vol 9 (7) ◽  
pp. 510-518 ◽  
Author(s):  
Frédéric Legros ◽  
Evi Chatzoglou ◽  
Paule Frachon ◽  
Hélène Ogier de Baulny ◽  
Pascal Laforêt ◽  
...  
Keyword(s):  
Cytochrome B ◽  
Functional Characterization ◽  
Cytochrome B Gene ◽  
Novel Mutations ◽  
Human Cytochrome

Functional Characterization of Novel Mutations Affecting Survivin (BIRC5)-Mediated Therapy Resistance in Head and Neck Cancer Patients

2012 ◽  
Vol 34 (2) ◽  
pp. 395-404 ◽  
Author(s):  
Shirley K. Knauer ◽  
Britta Unruhe ◽  
Sarah Karczewski ◽  
Rouven Hecht ◽  
Verena Fetz ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Functional Characterization ◽  
Therapy Resistance ◽  
Novel Mutations

Genetic Analysis of 17 Children with Hunter Syndrome: Identification and Functional Characterization of Four Novel Mutations in the Iduronate-2-Sulfatase Gene

2014 ◽  
Vol 41 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Dimitry A. Chistiakov ◽  
Lyudmila M. Kuzenkova ◽  
Kirill V. Savost'anov ◽  
Anait K. Gevorkyan ◽  
Alexander A. Pushkov ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Functional Characterization ◽  
Hunter Syndrome ◽  
Novel Mutations

scholarly journals Functional Characterization of Melanocortin-3 Receptor Variants Identify a Loss-of-Function Mutation Involving an Amino Acid Critical for G Protein-Coupled Receptor Activation

2004 ◽  
Vol 89 (8) ◽  
pp. 3936-3942 ◽  
Author(s):  
Ya-Xiong Tao ◽  
Deborah L. Segaloff
Keyword(s):  
G Protein ◽  
Functional Characterization ◽  
Receptor Activation ◽  
Dominant Negative ◽  
Supporting Evidence ◽  
Loss Of Function ◽  
Melanocortin 4 Receptor ◽  
Dominant Negative Activity ◽  
G Protein Coupled

Although melanocortin-4 receptor mutations are the cause of the most common monogenic form of obesity, the involvement of the melanocortin-3 receptor (MC3R) in the pathogenesis of obesity is unknown. Earlier studies failed to identify any mutations in obese patients except for the identification of two variants (K6T and I81V) that likely represent polymorphisms. However, a potential mutation (I183N) was recently reported from patients having high-fat contents. We report here the functional characterization of these variants. We show that K6T and I81V have ligand binding and signaling properties similar to wild-type (wt) MC3R, indicating that they are indeed polymorphisms. However, the other variant, I183N, completely lacks signaling in response to agonist stimulation, although it binds ligand with normal affinity and with only slightly decreased capacity. Coexpression of the wt and I183N MC3Rs showed that I183N does not exert dominant-negative activity on wt MC3R. These results provide supporting evidence for the hypothesis proposed in the original case report that MC3R mutation might be a genetic factor that confers susceptibility to obesity, likely due to haploinsufficiency. Further mutations at I183 revealed a discrete requirement for I183 in agonist-induced MC3R activation. The corresponding residue is also important for agonist-induced human melanocortin-4 receptor and lutropin receptor activation. In summary, we identify a residue that is critical for activation of G protein-coupled receptors.

Sign in / Sign up

Export Citation Format

Share Document