Cloning of a novel member of the low-density lipoprotein receptor family.
A gene encoding a novel transmembrane protein was identified by DNA sequence analysis within the insulin-dependent diabetes mellitus (IDDM) locus IDDM4 on chromosome 11q13. Based on its chromosomal position, this gene is a candidate for conferring susceptibility to diabetes. The gene, termed low-density lipoprotein receptor related protein 5 (LRP5), encodes a protein of 1615 amino acids that contains conserved modules which are characteristic of the low-density lipoprotein (LDL) receptor family. These modules include a putative signal peptide for protein export, four epidermal growth factor (EGF) repeats with associated spacer domains, three LDL-receptor (LDLR) repeats, a single transmembrane spanning domain, and a cytoplasmic domain. The encoded protein has a unique organization of EGF and LDLR repeats; therefore, LRP5 likely represents a new category of the LDLR family. Both human and mouse LRP5 cDNAs have been isolated and the encoded mature proteins are 95% identical, indicating a high degree of evolutionary conservation.
Hey
P J
PJ
Merck Research Laboratories, Department of Human Genetics, West Point, PA 19486, USA.
Twells
R C
RC
Phillips
M S
MS
Yusuke Nakagawa
Brown
S D
SD
Kawaguchi
Y
Y
Cox
R
R
Guochun Xie
Dugan
V
V
Hammond
H
H
Metzker
M L
ML
Todd
J A
JA
Hess
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular; D003360:Cosmids / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015698:Genomic Library; D006801:Humans; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D004269:DNA, Bacterial; D018076:DNA, Complementary; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D008565:Membrane Proteins; D011973:Receptors, LDL; D004247:DNA