Publication Date:
1997-07-11
Description:
Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carstea, E D -- Morris, J A -- Coleman, K G -- Loftus, S K -- Zhang, D -- Cummings, C -- Gu, J -- Rosenfeld, M A -- Pavan, W J -- Krizman, D B -- Nagle, J -- Polymeropoulos, M H -- Sturley, S L -- Ioannou, Y A -- Higgins, M E -- Comly, M -- Cooney, A -- Brown, A -- Kaneski, C R -- Blanchette-Mackie, E J -- Dwyer, N K -- Neufeld, E B -- Chang, T Y -- Liscum, L -- Strauss, J F 3rd -- Ohno, K -- Zeigler, M -- Carmi, R -- Sokol, J -- Markie, D -- O'Neill, R R -- van Diggelen, O P -- Elleder, M -- Patterson, M C -- Brady, R O -- Vanier, M T -- Pentchev, P G -- Tagle, D A -- New York, N.Y. -- Science. 1997 Jul 11;277(5323):228-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9211849" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
*Carrier Proteins
;
Cholesterol/*metabolism
;
Cholesterol, LDL/metabolism
;
Chromosome Mapping
;
Chromosomes, Human, Pair 18
;
Cloning, Molecular
;
*Drosophila Proteins
;
Homeostasis
;
Humans
;
Hydroxymethylglutaryl CoA Reductases/chemistry
;
Insect Proteins/chemistry
;
Intracellular Signaling Peptides and Proteins
;
Lysosomes/metabolism
;
*Membrane Glycoproteins
;
Membrane Proteins/chemistry
;
Molecular Sequence Data
;
Mutation
;
Niemann-Pick Diseases/*genetics/metabolism
;
Polymorphism, Single-Stranded Conformational
;
Proteins/chemistry/*genetics/physiology
;
Receptors, Cell Surface/chemistry
;
Sequence Homology, Amino Acid
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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