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The regulatory role of the kinase-homology domain in receptor guanylyl cyclases: Nothing ‘pseudo’ about it!

Mishra, V and Goel, R and Visweswariah, SS (2018) The regulatory role of the kinase-homology domain in receptor guanylyl cyclases: Nothing ‘pseudo’ about it! In: Biochemical Society Transactions, 46 (6). pp. 1729-1742.

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Official URL: https://doi.org/10.1042/BST20180472


The availability of genome sequence information and a large number of protein structures has allowed the cataloging of genes into various families, based on their function and predicted biochemical activity. Intriguingly, a number of proteins harbor changes in the amino acid sequence at residues, that from structural elucidation, are critical for catalytic activity. Such proteins have been categorized as ‘pseudoenzymes’. Here, we review the role of the pseudokinase (or kinase-homology) domain in receptor guanylyl cyclases. These are multidomain single-pass, transmembrane proteins harboring an extracellular ligand-binding domain, and an intracellular domain composed of a kinase-homology domain that regulates the activity of the associated guanylyl cyclase domain. Mutations that lie in the kinase-homology domain of these receptors are associated with human disease, and either abolish or enhance cGMP production by these receptors to alter downstream signaling events. This raises the interesting possibility that one could identify molecules that bind to the pseudokinase domain and regulate the activities of these receptors, in order to alleviate symptoms in patients harboring these mutations.

Item Type: Journal Article
Publication: Biochemical Society Transactions
Publisher: Portland Press Ltd
Additional Information: The copyright for this article belongs to the Portland Press Ltd.
Keywords: cyclic GMP; guanylate cyclase; guanylate cyclase C; guanylate cyclase D; guanylate cyclase E; guanylate cyclase F; guanylate cyclase G; natriuretic peptide receptor B; phosphotransferase; pseudokinase; unclassified drug; guanylate cyclase, priority journal; protein domain; Review; signal transduction; animal; genetics; human; metabolism; mutation; point mutation, Animals; Cyclic GMP; Guanylate Cyclase; Humans; Mutation; Point Mutation
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 03 Sep 2022 04:04
Last Modified: 03 Sep 2022 04:04
URI: https://eprints.iisc.ac.in/id/eprint/76387

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