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

Human Genomics, Apr 2016

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.

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

Loughner et al. Human Genomics Organization, evolution and functions of the human and mouse Ly6/uPAR family genes Chelsea L. Loughner 0 Elspeth A. Bruford 3 Monica S. McAndrews 2 Emili E. Delp 0 Sudha Swamynathan 0 Shivalingappa K. Swamynathan 0 1 4 5 6 0 Department of Ophthalmology, University of Pittsburgh School of Medicine , Pittsburgh , USA 1 Department of Cell Biology, University of Pittsburgh School of Medicine , Pittsburgh , USA 2 Mouse Genome Informatics, The Jackson Laboratory , Bar Harbor, ME 04609 , USA 3 HUGO Gene Nomenclature Committee (HGNC), European Bioinformatics Institute (EMBL-EBI) , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD , UK 4 Eye and Ear Institute, University of Pittsburgh School of Medicine , 203 Lothrop Street, Room 1025, Pittsburgh, PA 15213 , USA 5 Fox Center for Vision Restoration, University of Pittsburgh School of Medicine , Pittsburgh , USA 6 McGowan Institute of Regenerative Medicine, University of Pittsburgh , Pittsburgh , USA 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. Ly6/uPAR family; LU domain; Three-finger domain; uPAR; Lymphocytes; Neutrophils Introduction The lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) superfamily of structurally related proteins is characterized by the LU domain, an 80 amino acid domain containing ten cysteines arranged in a specific spacing pattern that allows distinct disulfide bridges which create the three-fingered (3F) structural motif [ 1, 2 ]. Ly6/uPAR proteins were first identified in the mouse over 35 years ago using antisera against lymphocytes [3]. Human homologs were subsequently isolated, leading to the recognition that they represent a well-conserved family with wide-ranging expression patterns and important functions. The fully annotated human and mouse genomes contain 35 and 61 Ly6/uPAR family members, respectively. Research over the last decade has begun to unravel the important functions of the encoded proteins. In this review, we provide an overview of the Ly6/uPAR gene family and their genomic organization, evolution, as well as functions, and provide a nomenclature system for the newly identified members of this family. Inclusion and approved nomenclature for novel Ly6/uPAR family members Although Ly6/uPAR family members are related by their structure, absence of a uniform naming convention resulted in arbitrary nomenclature for these genes as they were discovered. As many of the currently approved gene symbols for Ly6/uPAR family members (e.g., CD59 and PLAUR) have been widely used in the scientific literature for many years, we have refrained from a family-wide attempt to standardize their well-established names, avoiding the potential for additional confusion. In compiling this update, we came across many novel members of the Ly6/uPAR gene family, especially in the mouse genome, that did not yet have a systematic name. We named these novel family members in line with the Ly6/uPAR genes that they are most related to, based on a phylogenetic analysis (see below) using either the established LY6/Ly6# root for those that fell within the LY6 clades, or the LYPD/Lypd# (LY6/PLAUR domaincontaining) root for those outside the LY6 clades. The new symbols for these genes (1 human and 18 mouse), approved by the HGNC (HUGO Gene Nomenclature Committee) [ 4, 5 ] and MGNC (Mouse Genomic Nomenclature Committee) [6], are listed in Tables 1 and 2, respectively. We use the newly approved names for these genes in the rest of this update. HGNC have also created a gene family web-page for the human Ly6/uPAR family members (http://www.genenames.org/cgi-bin/genefamilies/set/1226). Genomic organization of the Ly6/uPAR gene family The Ly6/uPAR gene family currently includes 35 wellcharacterized human members, while the mouse gene family is considerably larger with 61 genes. Information including the name, chromosomal location, numbers of exons and LU domains for human and mouse family members is summarized in Tables 1 and 2, respectively. Twelve human Ly6 genes are clustered (...truncated)


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Chelsea Loughner, Elspeth Bruford, Monica McAndrews, Emili Delp, Sudha Swamynathan, Shivalingappa Swamynathan. Organization, evolution and functions of the human and mouse Ly6/uPAR family genes, Human Genomics, 2016, pp. 10, 10, DOI: 10.1186/s40246-016-0074-2