Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
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.
Carstea
E D
ED
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Morris
J A
JA
Coleman
K G
KG
Loftus
S K
SK
Zhang
D
D
Cummings
C
C
Gu
J
J
Rosenfeld
M A
MA
Pavan
W J
WJ
Krizman
D B
DB
Nagle
J
J
Polymeropoulos
M H
MH
Sturley
S L
SL
Ioannou
Y A
YA
Higgins
M E
ME
Comly
M
M
Cooney
A
A
Brown
A
A
Kaneski
C R
CR
Blanchette-Mackie
E J
EJ
Dwyer
N K
NK
Neufeld
E B
EB
Chang
T Y
TY
Liscum
L
L
Strauss
J F
JF
Ohno
K
K
Zeigler
M
M
Carmi
R
R
Sokol
J
J
Markie
D
D
O'Neill
R R
RR
van Diggelen
O P
OP
Elleder
M
M
Patterson
M C
MC
Brady
R O
RO
Vanier
M T
MT
Pentchev
P G
PG
Tagle
D A
DA
D000595:Amino Acid Sequence; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D006706:Homeostasis; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D002352:Carrier Proteins; D008078:Cholesterol, LDL; D029721:Drosophila Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins; D011956:Receptors, Cell Surface; C102196:SREBP cleavage-activating protein; C070844:ptc protein, Drosophila; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases