Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

Cummings, Nik; Shields, Katherine A.; Curran, Joanne E.; Bozaoglu, Kiymet; Trevaskis, James L.; Gluschenko, K.; Cai, Guowen; Comuzzie, Anthony G.; Dyer, Thomas D.; Walder, Ken; Zimmet, Paul; Collier, Greg R.; Blangero, John; Jowett, Jeremy B. M.

doi:10.1038/ijo.2011.67

Cited by 20 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its suppression decreased body weight in obese mice via reduced food intake [95]. In line with this, SGIP1 was associated with measures of obesity such as fat mass in humans [96,97]. Besides, it was linked to alterations in EEG and ECG characteristics and to alcoholism.…”

Section: Links Of Muniscin Proteins To Human Diseasementioning

confidence: 63%

Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations

Tehran

López-Hernández

Maritzen

2019

Cells

View full text Add to dashboard Cite

Cells need to exchange material and information with their environment. This is largely achieved via cell-surface receptors which mediate processes ranging from nutrient uptake to signaling responses. Consequently, their surface levels have to be dynamically controlled. Endocytosis constitutes a powerful mechanism to regulate the surface proteome and to recycle vesicular transmembrane proteins that strand at the plasma membrane after exocytosis. For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. In line with the importance of endocytosis for nutrient uptake, cell signaling and neurotransmission, animal models and human mutations have revealed that defects in these adaptors are associated with several diseases ranging from metabolic disorders to encephalopathies. This review will discuss the physiological functions of the so far known adaptor proteins and will provide a comprehensive overview of their links to human diseases.

show abstract

Section: Links Of Muniscin Proteins To Human Diseasementioning

confidence: 63%

Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations

Tehran

López-Hernández

Maritzen

2019

Cells

View full text Add to dashboard Cite

show abstract

“…Thus, the predicted functions of SGIP1/SGIP1α discussed above may operate only in the brain. SGIP1 is implicated in energy homeostasis and obesity in mice, rats, and humans 18 35 . These findings suggest the hypothetical role of SGIP1/SGIP1α in the CME of specific cargo in the brain, which ultimately controls the feeding behavior of mammals.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain

Shimada

Yamaguchi

Kohda

2016

Sci Rep

View full text Add to dashboard Cite

FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their μ homology domains (μHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity μHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal μHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 μHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the μHD, which is distinct from those of other distantly related μHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the μHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in μHD binding.

show abstract

“…rs7526812 T>C is located ~15kb downstream from, and is in strong linkage disequilibrium ( r 2 = 1.0) with, a variant in the miR-3117 gene locus (rs12402181). rs7526812 T>C is also a missense polymorphism situated within an exon of the SGIP gene, which has been genetically linked to fat mass [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium

et al. 2015

View full text Add to dashboard Cite

Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.

show abstract

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

Cited by 20 publications

References 31 publications

Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations

Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations

Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium

Contact Info

Product

Resources

About