Organization, evolution and functions of the human and mouse Ly6/uPAR family genes

Abstract

Members of the lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily of proteins are cysteine-rich proteins characterized by a distinct disulfide bridge pattern that creates the three-finger Ly6/uPAR (LU) domain. Although the Ly6/uPAR family proteins share a common structure, their expression patterns and functions vary. To date, 35 human and 61 mouse Ly6/uPAR family members have been identified. Based on their subcellular localization, these proteins are further classified as GPI-anchored on the cell membrane, or secreted. The genes encoding Ly6/uPAR family proteins are conserved across different species and are clustered in syntenic regions on human chromosomes 8, 19, 6 and 11, and mouse Chromosomes 15, 7, 17, and 9, respectively. Here, we review the human and mouse Ly6/uPAR family gene and protein structure and genomic organization, expression, functions, and evolution, and introduce new names for novel family members.

Keywords: LU domain; Ly6/uPAR family; Lymphocytes; Neutrophils; Three-finger domain; uPAR.

Fig. 1

Structure of a typical Ly6/UPAR family gene and alignment of amino acid sequences of selected LU domains. a Structure of a typical LY6/UPAR family gene, showing three exons (E-1, E-2 and E-3), two introns (I-1 and I-2), and the location of signal peptide as well as GPI-anchor domain. b Alignment of LU domain amino acid sequences of selected human LY6/UPAR proteins. GPI-anchored (top) and secreted (bottom) proteins are clustered together, with an empty line in between. Alignments were performed using ProbCons in Bioinformatics toolkit provided by Max-Planck Institute for Developmental Biology (http://toolkit.tuebingen.mpg.de). Conserved cysteines linked by non-variant disulfide bridges are highlighted in similar colors. Isoforms are denoted with a dash and the isoform name (e.g. LY6G6D-A). LYNX1-C and SLURP2 are precursor forms of the final protein. NTS, Non-translated sequence

Fig. 2

Phylogram revealing the evolutionary relationship among mouse (ms-) and human (hu-) Ly6/uPAR family proteins. The phylogram was generated using the amino acid sequences in Clustal-Omega web-based program [106, 107] (http://www.ebi.ac.uk/Tools/msa/clustalo/). The display was generated using the methods described [108]. The length of each branch from the most recent branch point indicates the evolutionary distance, or the relative period of time the protein has been in its current state. Known GPI-anchored Ly6/uPAR family proteins are shown in red, and those secreted (without GPI-anchor) are shown in green. Those predicted to contain a GPI-anchor (but not yet experimentally proven) are in purple, and those predicted to not contain a GPI-anchor sequence (but not yet experimentally proven) are in black. Novel genes named in this study are indicated with an asterisk (*)