Evolution and Medical Significance of LU Domain-Containing Proteins

TY - JOUR

T1 - Evolution and Medical Significance of LU Domain-Containing Proteins

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

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

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.

U2 - 10.3390/ijms20112760

DO - 10.3390/ijms20112760

M3 - Review

C2 - 31195646

SN - 1424-6783

VL - 20

SP - 1

EP - 20

JO - International Journal of Molecular Sciences (CD-ROM)

JF - International Journal of Molecular Sciences (CD-ROM)

IS - 11

ER -