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MGP001810

UniProt Annotations

Entry Information
Gene Namelow density lipoprotein receptor
Protein EntryLDLR_HUMAN
UniProt IDP01130
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=6; Name=1; IsoId=P01130-1; Sequence=Displayed; Name=2; IsoId=P01130-2; Sequence=VSP_043053, VSP_043054; Note=No experimental confirmation available.; Name=3; IsoId=P01130-3; Sequence=VSP_055014, VSP_055015; Note=No experimental confirmation available.; Name=4; IsoId=P01130-4; Sequence=VSP_043595; Note=No experimental confirmation available.; Name=5; IsoId=P01130-5; Sequence=VSP_045525; Note=No experimental confirmation available.; Name=6; IsoId=P01130-6; Sequence=VSP_047413; Note=No experimental confirmation available.;
DiseaseFamilial hypercholesterolemia (FH) [MIM:143890]: Common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis). {ECO:0000269|PubMed:10090484, ECO:0000269|PubMed:10206683, ECO:0000269|PubMed:10422803, ECO:0000269|PubMed:10447263, ECO:0000269|PubMed:10660340, ECO:0000269|PubMed:10882754, ECO:0000269|PubMed:10978268, ECO:0000269|PubMed:10980548, ECO:0000269|PubMed:11298688, ECO:0000269|PubMed:1446662, ECO:0000269|PubMed:1464748, ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:19319977, ECO:0000269|PubMed:22160468, ECO:0000269|PubMed:2318961, ECO:0000269|PubMed:2569482, ECO:0000269|PubMed:2726768, ECO:0000269|PubMed:3263645, ECO:0000269|PubMed:3955657, ECO:0000269|PubMed:7550239, ECO:0000269|PubMed:7573037, ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:7635461, ECO:0000269|PubMed:7635482, ECO:0000269|PubMed:7649546, ECO:0000269|PubMed:7649549, ECO:0000269|PubMed:8168830, ECO:0000269|PubMed:8347689, ECO:0000269|PubMed:8462973, ECO:0000269|PubMed:8664907, ECO:0000269|PubMed:8740918, ECO:0000269|PubMed:9026534, ECO:0000269|PubMed:9104431, ECO:0000269|PubMed:9143924, ECO:0000269|PubMed:9254862, ECO:0000269|PubMed:9259195, ECO:0000269|PubMed:9452094, ECO:0000269|PubMed:9452095, ECO:0000269|PubMed:9452118, ECO:0000269|PubMed:9654205, ECO:0000269|PubMed:9678702, ECO:0000269|PubMed:9852677, ECO:0000269|Ref.66}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe NPXY motif mediates the interaction with the clathrin adaptor DAB2 involved in receptor internalization. {ECO:0000250}.
FunctionBinds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
InteractionP04114:APOB; NbExp=4; IntAct=EBI-988319, EBI-3926040; P02649:APOE; NbExp=2; IntAct=EBI-988319, EBI-1222467; Q8NBP7:PCSK9; NbExp=9; IntAct=EBI-988319, EBI-7539251;
PtmN- and O-glycosylated. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19520913}.
PtmUbiquitinated by MYLIP leading to degradation. {ECO:0000269|PubMed:19520913}.
Sequence CautionSequence=BAD92646.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the LDLR family. {ECO:0000305}.
SimilarityContains 3 EGF-like domains. {ECO:0000255|PROSITE- ProRule:PRU00076}.
SimilarityContains 6 LDL-receptor class B repeats. {ECO:0000255|PROSITE-ProRule:PRU00461}.
SimilarityContains 7 LDL-receptor class A domains. {ECO:0000255|PROSITE-ProRule:PRU00124}.
Subcellular LocationCell membrane; Single-pass type I membrane protein. Endomembrane system; Single-pass type I membrane protein. Membrane, clathrin-coated pit; Single-pass type I membrane protein. Golgi apparatus. Early endosome. Late endosome. Cell surface. Lysosome. Note=Found distributed from the plasma membrane to intracellular compartments. Localizes to the Golgi apparatus, early and late endosomes/lysosomes and cell surface in the presence of PCSK9.
SubunitInteracts with LDLRAP1, ARRB1, SNX17. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts with the full length immature form of PCSK9 (via C-terminus). Interacts with HCV E1/E2 heterodimer. Interacts with HIV-1 Tat. {ECO:0000269|PubMed:11100124, ECO:0000269|PubMed:12221107, ECO:0000269|PubMed:12615904, ECO:0000269|PubMed:12944399, ECO:0000269|PubMed:14739284, ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:21149300}.
Web ResourceName=LDLR; Note=LDLR mutation database; URL="http://www.ucl.ac.uk/fh/";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=LDLR";
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