title: Single-gene disorders: what role could moonlighting enzymes play?
abstract: Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be an easy prediction of the phenotype from the genotype, which has been shown for a number of metabolic disorders. We propose that moonlighting enzymes (i.e., metabolic enzymes with additional functional activities) could contribute to the complexity of such disorders. The lack of knowledge about the additional functional activities of proteins could result in a lack of correlation between genotype and phenotype. In this review, we highlight some notable and recent examples of moonlighting enzymes and their possible contributions to human disease. Because knowledge and cataloging of the moonlighting activities of proteins are essential for the study of cellular function and human physiology, we also review recently reported and recommended methods for the discovery of moonlighting activities.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7088, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Sriram
authors.forename: Julian A
authors.initials: JA
authors.lastname: Martinez
authors.forename: Edward R B
authors.initials: ER
authors.lastname: McCabe
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Dipple
mesh_terms: D000818:Animals; D017209:Apoptosis; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D009097:Multienzyme Complexes; D011506:Proteins