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)