Publication Date:
2001-04-28
Description:
Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, C K -- Wilund, K -- Arca, M -- Zuliani, G -- Fellin, R -- Maioli, M -- Calandra, S -- Bertolini, S -- Cossu, F -- Grishin, N -- Barnes, R -- Cohen, J C -- Hobbs, H H -- E.0565/Telethon/Italy -- HL07360/HL/NHLBI NIH HHS/ -- P0I-HL2048/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 May 18;292(5520):1394-8. Epub 2001 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McDermott Center for Human Growth and Development and Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11326085" target="_blank"〉PubMed〈/a〉
Keywords:
Adolescent
;
Adult
;
Amino Acid Sequence
;
Binding Sites
;
Carrier Proteins/chemistry/*genetics/*metabolism
;
Child
;
Child, Preschool
;
Chromosome Mapping
;
Chromosomes, Human, Pair 1/*genetics
;
Cloning, Molecular
;
Exons/genetics
;
Female
;
Fibroblasts
;
Genes, Recessive/*genetics
;
Homozygote
;
Humans
;
Hypercholesterolemia/*genetics/metabolism/physiopathology
;
Introns/genetics
;
Italy
;
Lebanon
;
Liver/metabolism
;
Male
;
Middle Aged
;
Molecular Sequence Data
;
Mutation/*genetics
;
Organ Specificity
;
Pedigree
;
Phosphotyrosine/metabolism
;
Protein Binding
;
RNA, Messenger/analysis/genetics
;
Receptors, LDL/*metabolism
;
Sequence Alignment
;
Two-Hybrid System Techniques
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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