Lipoproteins (VLDLR) Protein

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]

VLDLR: Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation. Defects in VLDLR are the cause of cerebellar ataxia mental retardation and dysequilibrium syndrome type 1 (CMARQ1); also known as dysequilibrium syndrome (DES) or non- progressive cerebellar disorder with mental retardation. CMARQ1 is a congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation and cerebellar hypoplasia. Additional features include short stature, strabismus, pes planus and, rarely, seizures. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Membrane protein, integral; Receptor, misc.

Chromosomal Location of Human Ortholog: 9p24.2

Cellular Component: lysosomal membrane; membrane; plasma membrane; receptor complex

Molecular Function: apolipoprotein binding; calcium-dependent protein binding; glycoprotein binding; low-density lipoprotein receptor activity; protein binding; very-low-density lipoprotein binding; very-low-density lipoprotein receptor activity

Biological Process: axon guidance; low-density lipoprotein receptor catabolic process; memory; negative regulation of transcription from RNA polymerase II promoter; nervous system development; receptor-mediated endocytosis; signal transduction

Disease: Cerebellar Ataxia, Mental Retardation, And Dysequilibrium Syndrome 1