Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal cell development depends to a large part on multifunctional proteins that have evolved by recombination of proven modular elements. We now have discovered and characterized in rabbit such a multi-domain protein, and classify it as novel member of the low density lipoprotein (LDL) receptor gene family. The extracellular portion of the approximately 250-kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated-pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, in particular the hippocampus, dentate gyrus, and cerebral cortex, and is present at significant levels in liver, adrenal glands, and testis. Western blotting of tissues and ligand blotting of LR11-transfected cells demonstrated that the novel protein binds apolipoprotein E-containing lipoproteins. In contrast to the LDL receptor, hepatic expression of LR11 is unaffected by hyperlipidemia. The identification of this highly conserved and superbly complex protein offers the opportunity to gain new insights into the emergence of multifunctional mosaic proteins akin to the ever expanding LDL receptor gene family.
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PMID:Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member. 879 46

We now have discovered and characterized a novel multi-domain protein and classified it as a member of the LDL receptor gene family. The approximately 250 kDa membrane protein, termed LR11, highly conserved in man, rabbit and chicken, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, liver and adrenal glands. Ligand blotting of LR11-transfected cells demonstrated that LR11 binds apolipoproteinE-containing lipoproteins, as well as other members of LDL receptor gene family. In contrast to the LDL receptor, the mRNA levels in rabbit liver is unaffected by hyperlipidemia. The features of this highly conserved and complex mosaic protein suggest the importance of the ever expanding LDL receptor gene family in the evolution and proposed multifunctionality.
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PMID:A novel member of the LDL receptor gene family with eleven binding repeats is structurally related to neural adhesion molecules and a yeast vacuolar protein sorting receptor. 958 50