Dataset Information

Identification of FAME (Factor Associated with Metabolism and Energy) interactome

ABSTRACT: Using comparative genomics, we discovered that a previously uncharacterized gene (1700011H14RIK/C14ORF105/CCDC198) hereby named FAME (Factor Associated with Metabolism and Energy) shows an unusually high rate of evolutionary divergence in birds and mammals. By comparing SNVs, we identified gene-flow of FAME from Neandertals into modern humans. FAME knockout animals demonstrated increased body weight and decreased energy expenditure, corresponding to GWAS linking FAME with higher BMI, diabetes-related pathologies, and macular degeneration in humans. The analysis of gene expression and subcellular localization revealed that FAME is a membrane-bound protein enriched in kidneys. Although a gene knockout resulted in structurally normal kidneys, we detected higher Albumin in urine and lowered ferritin in the blood. The experiment confirmed interactions between FAME and ferritin and showed co-localization in vesicular and plasma membranes. Overall, our results show that FAME plays a role in tuning metabolite excretion and energy expenditure, partly explaining why it evolves at a high rate in birds and mammals. Here, we provide data related to identification of FAME interactome using the co-immunoprecipitation method.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: David Potesil

LAB HEAD: Zbynek Zdrahal

PROVIDER: PXD039259 | Pride | 2023-07-20

REPOSITORIES: Pride

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Publications

A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.

Petersen Julian J Englmaier Lukas L Artemov Artem V AV Poverennaya Irina I Mahmoud Ruba R Bouderlique Thibault T Tesarova Marketa M Deviatiiarov Ruslan R Szilvásy-Szabó Anett A Akkuratov Evgeny E EE Pajuelo Reguera David D Zeberg Hugo H Kaucka Marketa M Kastriti Maria Eleni ME Krivanek Jan J Radaszkiewicz Tomasz T Gömöryová Kristína K Knauth Sarah S Potesil David D Zdrahal Zbynek Z Ganji Ranjani Sri RS Grabowski Anna A Buhl Miriam E ME Zikmund Tomas T Kavkova Michaela M Axelson Håkan H Lindgren David D Kramann Rafael R Kuppe Christoph C Erdélyi Ferenc F Máté Zoltán Z Szabó Gábor G Koehne Till T Harkany Tibor T Fried Kaj K Kaiser Jozef J Boor Peter P Fekete Csaba C Rozman Jan J Kasparek Petr P Prochazka Jan J Sedlacek Radislav R Bryja Vitezslav V Gusev Oleg O Adameyko Igor I

Nature communications 20230529 1

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decre ...[more]

PMID: 37248239

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Project description:During the evolution of vertebrates, specific molecular innovations ensured adaptations which resulted in the split of different animal groups. Here comparative genomic analysis became a valued instrument to identify genes associated with the divergence of taxa and speciation events. Using this approach, we identified the association of the previously uncharacterized gene (mouse (1700011H14RIK, human C14ORF105/CCDC198), hereby named Kamp (Kidney-associated membrane protein) with the evolutionary split leading to birds and mammals. Furthermore, by comparing single nuclear polymorphisms of modern humans with Neandertals at the locus of Kamp, we identified gene-flow of Kamp from Neandertals into modern humans. Analyzing the expression of Kamp in humans revealed a restriction to the kidney, pancreas, and few other organs. A knockout of this gene in mice resulted in a structurally normal kidney as validated with micro-computed microtomography scans and single-cell transcriptomics, but with higher Albumin levels in the urine lower serum ferritin levels. Further, interactomics screening revealed an interaction between KAMP and ferritin (heavy chain), which was cross-validated by the analysis of co-localization of both proteins in vesicular and plasma membranes. The membranal localization of KAMP appeared regulated by its N-terminal myristoylation site, as KAMP became cytoplasmic in the absence of this specific sequence. Kamp knockout animals demonstrated increased body weight and decreased energy expenditure. This corresponded to Genome-Wide Association Studies of Kamp linked with higher BMI, diabetes-related pathologies, and macular degeneration in humans. Subsequent gain-of-function experiments showed altered proliferative dynamics and accumulation of KAMP during mitosis. Bioinformatics analysis indicated a protective role of KAMP in renal and liver cancer progression, as suggested by an association of KAMP with epithelial-to-mesenchymal transition and altered localization in tumors versus healthy tissue. Altogether, our results revealed several important roles played by KAMP in a vertebrate body, with specific emphasis on metabolite excretion and energy expenditure.

Dataset Information

Identification of FAME (Factor Associated with Metabolism and Energy) interactome

Publications

A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.

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