Three-finger proteins from the Ly6/uPAR family: Functional diversity within one structural motif

Abstract

The discovery in higher animals of proteins from the Ly6/uPAR family, which have structural homology with snake "three-finger" neurotoxins, has generated great interest in these molecules and their role in the functioning of the organism. These proteins have been found in the nervous, immune, endocrine, and reproductive systems of mammals. There are two types of the Ly6/uPAR proteins: those associated with the cell membrane by GPI-anchor and secreted ones. For some of them (Lynx1, SLURP-1, SLURP-2, Lypd6), as well as for snake α-neurotoxins, the target of action is nicotinic acetylcholine receptors, which are widely represented in the central and peripheral nervous systems, and in many other tissues, including epithelial cells and the immune system. However, the targets of most proteins from the Ly6/uPAR family and the mechanism of their action remain unknown. This review presents data on the structural and functional properties of the Ly6/uPAR proteins, which reveal a variety of functions within a single structural motif.

Human secreted proteins SLURP‐1 and SLURP‐2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors

“…Higher animals produce endogenous proteins from the Ly6/uPAR family, which share structural homology with snake α‐neurotoxins acting on nicotinic acetylcholine receptors (nAChRs) (Loughner et al ., ; Vasilyeva et al ., ). Some of these proteins, such as Lynx1 and Lypd6 in the brain, are membrane‐tethered, whereas others such as the secreted Ly6/uPAR proteins SLURP‐1 and SLURP‐2, are secreted by epithelial tissues and probably involved in the development of a number of skin diseases including Mal de Meleda (Allan et al ., ; Perez and Khachemoune, ) and psoriasis (Tsuji et al ., ).…”

Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors

“…Ly-6/uPAR proteins or ‘three-finger’ proteins (TFPs) contain characteristic ‘three-finger’ domain(s) or LU-domain(s) [ 1 ]. Each LU-domain is composed of a compact disulfide-stabilized β-structural core (‘head’) and three protruding loops (‘fingers’).…”

Agr2‐interacting Prod1‐like protein Tfp4 from Xenopus laevis is necessary for early forebrain and eye development as well as for the tadpole appendage regeneration

“…To clarify the evolutionary relationships between Tfps1‐6 (GeneBank accession No: Tfp1 [CD59]—MK060020; Tfp2—MK060015; Tfp3—MK060016; Tfp4—MK060017; Tfp5—MK060018; Tfp6—MK060019), that we have identified in X. laevis , and Prod1, CD59, and Lypd6, we have performed the alignment and clustering analyses with these proteins from different species. First, the alignment demonstrated the presence in Tfp4 protein of all conserved cysteines, crucial for the functioning of the three‐fingers proteins (Vasilyeva, Loktyushov, Bychkov, Shenkarev, & Lyukmanova, ) (Figure a). Second, clustering of Tfp1‐6 with Prod1, CD59 and Lypd6 revealed that different Tfps cluster with different members of the CD59/lypd6 superfamily (Figure b).…”