Evolution and Medical Significance of LU Domain-Containing Proteins

Julie Maja Leth; Katrine Zinck Leth-Espensen; Kristian Kølby Kristensen; Anni Kumari; Anne-Marie Lund Winther; Stephen G Young; Michael Ploug

doi:10.3390/ijms20112760

Evolution and Medical Significance of LU Domain-Containing Proteins

Julie Maja Leth, Katrine Zinck Leth-Espensen, Kristian Kølby Kristensen, Anni Kumari, Anne-Marie Lund Winther, Stephen G Young, Michael Ploug

8 Citations (Scopus)

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Abstract

Proteins containing Ly6/uPAR (LU) domains exhibit very diverse biological functions and have broad taxonomic distributions in eukaryotes. In general, they adopt a characteristic three-fingered folding topology with three long loops projecting from a disulfide-rich globular core. The majority of the members of this protein domain family contain only a single LU domain, which can be secreted, glycolipid anchored, or constitute the extracellular ligand binding domain of type-I membrane proteins. Nonetheless, a few proteins contain multiple LU domains, for example, the urokinase receptor uPAR, C4.4A, and Haldisin. In the current review, we will discuss evolutionary aspects of this protein domain family with special emphasis on variations in their consensus disulfide bond patterns. Furthermore, we will present selected cases where missense mutations in LU domain-containing proteins leads to dysfunctional proteins that are causally linked to genesis of human disease.

Original language	English
Journal	International Journal of Molecular Sciences
Volume	20
Issue number	11
Pages (from-to)	1-20
Number of pages	20
ISSN	1424-6783
DOIs	https://doi.org/10.3390/ijms20112760
Publication status	Published - 1 Jun 2019

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Evolution and Medical Significance of LU Domain−Containing ProteinsFinal published version, 6.53 MBLicence: CC BY

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abstract = "Proteins containing Ly6/uPAR (LU) domains exhibit very diverse biological functions and have broad taxonomic distributions in eukaryotes. In general, they adopt a characteristic three-fingered folding topology with three long loops projecting from a disulfide-rich globular core. The majority of the members of this protein domain family contain only a single LU domain, which can be secreted, glycolipid anchored, or constitute the extracellular ligand binding domain of type-I membrane proteins. Nonetheless, a few proteins contain multiple LU domains, for example, the urokinase receptor uPAR, C4.4A, and Haldisin. In the current review, we will discuss evolutionary aspects of this protein domain family with special emphasis on variations in their consensus disulfide bond patterns. Furthermore, we will present selected cases where missense mutations in LU domain-containing proteins leads to dysfunctional proteins that are causally linked to genesis of human disease.",

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AU - Leth, Julie Maja

AU - Leth-Espensen, Katrine Zinck

AU - Kristensen, Kristian Kølby

AU - Kumari, Anni

AU - Lund Winther, Anne-Marie

AU - Young, Stephen G

AU - Ploug, Michael

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AB - Proteins containing Ly6/uPAR (LU) domains exhibit very diverse biological functions and have broad taxonomic distributions in eukaryotes. In general, they adopt a characteristic three-fingered folding topology with three long loops projecting from a disulfide-rich globular core. The majority of the members of this protein domain family contain only a single LU domain, which can be secreted, glycolipid anchored, or constitute the extracellular ligand binding domain of type-I membrane proteins. Nonetheless, a few proteins contain multiple LU domains, for example, the urokinase receptor uPAR, C4.4A, and Haldisin. In the current review, we will discuss evolutionary aspects of this protein domain family with special emphasis on variations in their consensus disulfide bond patterns. Furthermore, we will present selected cases where missense mutations in LU domain-containing proteins leads to dysfunctional proteins that are causally linked to genesis of human disease.

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Evolution and Medical Significance of LU Domain-Containing Proteins

Abstract

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