Renalase—A new understanding of its enzymatic and non‐enzymatic activity and its implications for future research

Abstract

Renalase was first described in 2005 by the research team of Gary V.Desir who aimed to find additional proteins that may be involved in endocrine function of the kidneys. 1 To do so, the scientists searched the Mammalian Gene Collection (MCG) for genes that: encode proteins, have <20% sequence similarity to known proteins, contain a signal peptide sequence and do not contain transmembrane domains. Their initial search identified 114 candidate genes encoding novel secretory proteins; however, in further Northern blot analysis only one of them was preferably expressed in human kidney.The cDNA of this gene was then applied to the Human Genome Project database, identified to residue on chromosome 10 at q23.33 and named renalase. 1 Further analysis of the gene showed that it encompasses ~309,469 base pairs (bp), has 10 exons and at least four alternatively spliced isoforms with renalase1 being the most highly expressed. 2 The protein encoded by renalase1 is the most abundant one in the human body and can be detected in plasma, kidney, heart, skeletal muscle and liver. 2 The fact that it incorporates three main functional domains (i.e., a signal peptide, a flavin adenine dinucleotide (FAD)-binding region and an amine oxidase domain) (Figure 1) became the basis for its classification as a novel flavin adenine dinucleotide-dependent amine oxidase. 1,2 The main representatives of this group are monoamine oxidases A and B (MAO-A and MAO-B), both known to catalyse the intracellular oxidation of monoamine neurotransmitters, such as dopamine, serotonin, epinephrine and norepinephrine. 3 This prompted scientists to hypothesize that renalase is a sister enzyme to MAO-A and MAO-B and is also engaged into the oxidation of neurotransmitters, but unlike aforementioned enzymes it is secreted into plasma and acts

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