Source:http://linkedlifedata.com/resource/pubmed/id/12576321
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2003-5-20
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pubmed:databankReference | |
pubmed:abstractText |
Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis affecting 3 related organelles-melanosomes, platelet dense bodies, and lysosomes. Four genes causing HPS in humans (HPS1-HPS4) are known, and at least 15 nonallelic mutations cause HPS in the mouse. Where their functions are known, the HPS-associated proteins are involved in some aspect of intracellular vesicular trafficking, that is, protein sorting and vesicle docking and fusion. Biochemical and genetic evidence indicates that the HPS-associated genes encode components of at least 3 distinct protein complexes: the adaptor complex AP-3; the HPS1/HPS4 complex; and BLOC-1 (biogenesis of lysosome-related organelles complex-1), consisting of the proteins encoded at 2 mouse HPS loci, pallid (pa) and muted (mu), and at least 3 other unidentified proteins. Here, we report the cloning of the mouse HPS mutation cappuccino (cno). We show that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno/cno mice. The C-terminal 81 amino acids are replaced with 72 different amino acids in the mutant CNO protein, and its ability to interact in BLOC-1 is abolished. We performed mutation screening of patients with HPS and failed to identify any CNO defects. Notably, although defects in components of the HPS1/HPS4 and the AP-3 complexes are associated with HPS in humans, no defects in the known components of BLOC-1 have been identified in 142 patients with HPS screened to date, suggesting that BLOC-1 function may be critical in humans.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/PLDN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pldn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4402-7
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pubmed:dateRevised |
2011-2-9
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pubmed:meshHeading |
pubmed-meshheading:12576321-Amino Acid Sequence,
pubmed-meshheading:12576321-Animals,
pubmed-meshheading:12576321-Carrier Proteins,
pubmed-meshheading:12576321-DNA Mutational Analysis,
pubmed-meshheading:12576321-Fibroblasts,
pubmed-meshheading:12576321-Hermanski-Pudlak Syndrome,
pubmed-meshheading:12576321-Humans,
pubmed-meshheading:12576321-Lectins,
pubmed-meshheading:12576321-Mice,
pubmed-meshheading:12576321-Molecular Sequence Data,
pubmed-meshheading:12576321-Mutation,
pubmed-meshheading:12576321-Protein Binding,
pubmed-meshheading:12576321-Tissue Distribution,
pubmed-meshheading:12576321-Vesicular Transport Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1).
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pubmed:affiliation |
The Jackson Laboratory, Bar Harbor, ME 04609, USA. luanne@jax.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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