The low-density lipoprotein receptor (LDLR) is a single-pass type I transmembrane endocytic receptor, most abundant on hepatocytes, that binds apolipoprotein B-100 on LDL and apolipoprotein E on VLDL remnants through seven calcium-dependent LDL-A repeats. Receptors cluster in clathrin-coated pits, where the cytoplasmic FxNPxY signal is recognized by the adaptors AP-2 and ARH (LDLRAP1), and are internalized. In the acidic early endosome the EGF-precursor homology domain (beta-propeller) displaces the ligand, which proceeds to lysosomes for hydrolysis, while the receptor recycles to the surface. Hepatic LDLR is the main route of plasma LDL clearance and of cellular cholesterol import, and its abundance is set by SREBP-2 transcription and by post-translational degradation driven by PCSK9 binding to the EGF-A repeat and by IDOL-mediated ubiquitination. Loss-of-function variants cause familial hypercholesterolemia. LDLR also serves as an entry receptor for several viruses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001523 retinoid metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Retinoid metabolism is an indirect phenotype. Reason: Remnant lipoproteins carrying retinyl esters can be taken up through LDLR, but LDLR does not participate in retinoid metabolism. |
| GO:0001540 amyloid-beta binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Amyloid-beta binding reported from rodent/brain studies; non-core. Reason: LDLR has been reported to bind and internalize amyloid-beta in brain cells (rodent-derived ISS/IEA). Plausible as receptor-mediated uptake but peripheral to LDLR's lipoprotein receptor role. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:0001540 amyloid-beta binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Amyloid-beta binding reported from rodent/brain studies; non-core. Reason: LDLR has been reported to bind and internalize amyloid-beta in brain cells (rodent-derived ISS/IEA). Plausible as receptor-mediated uptake but peripheral to LDLR's lipoprotein receptor role. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:0001920 negative regulation of receptor recycling | IDA PMID:17452316 Binding of proprotein convertase subtilisin/kexin type 9 to ... | MARK AS OVER ANNOTATED | Summary: LDLR is the receptor whose recycling is inhibited, not the regulator. Reason: In this study PCSK9 binding to the LDLR EGF-A repeat prevents LDLR recycling. The regulator is PCSK9; LDLR is the regulated cargo, so the regulation term describes the partner's role. Supporting Evidence: PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0002020 protease binding | IPI PMID:22081141 Mechanistic implications for LDL receptor degradation from t... | KEEP AS NON CORE | Summary: PCSK9 binding is real but describes LDLR as a regulatory target. Reason: The EGF-A repeat of LDLR is bound by PCSK9, a non-catalytic regulator in this context, which redirects the receptor to lysosomes. The interaction is well established structurally, but it is a regulatory input acting on LDLR rather than an LDLR function. Supporting Evidence: PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. |
| GO:0002020 protease binding | IPI PMID:22081141 Mechanistic implications for LDL receptor degradation from t... | KEEP AS NON CORE | Summary: PCSK9 binding is real but describes LDLR as a regulatory target. Reason: The EGF-A repeat of LDLR is bound by PCSK9, a non-catalytic regulator in this context, which redirects the receptor to lysosomes. The interaction is well established structurally, but it is a regulatory input acting on LDLR rather than an LDLR function. Supporting Evidence: PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. |
| GO:0002020 protease binding | IPI PMID:22848640 Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-... | KEEP AS NON CORE | Summary: PCSK9 binding is real but describes LDLR as a regulatory target. Reason: The EGF-A repeat of LDLR is bound by PCSK9, a non-catalytic regulator in this context, which redirects the receptor to lysosomes. The interaction is well established structurally, but it is a regulatory input acting on LDLR rather than an LDLR function. Supporting Evidence: PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. |
| GO:0005041 low-density lipoprotein particle receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | IC PMID:22848640 Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-... | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | IDA PMID:6091915 The human LDL receptor: a cysteine-rich protein with multipl... | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | IDA PMID:8626535 Human apolipoprotein E receptor 2. A novel lipoprotein recep... | ACCEPT | Summary: LDL receptor activity used as comparator in an apoER2 study. Reason: The study characterizes apoER2 and compares it with the LDL receptor; the LDLR activity itself is independently well established, so the curator's annotation is accepted. Supporting Evidence: PMID:8626535 The new receptor consists of five functional domains resembling the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) receptors. PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005041 low-density lipoprotein particle receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005041 low-density lipoprotein particle receptor activity | TAS PMID:2777800 Analysis of a recycling-impaired mutant of low density lipop... | ACCEPT | Summary: Core function: LDLR is the prototypical LDL particle receptor. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. Functional receptor expression after cDNA transfection, and FH alleles that abolish LDL binding or surface delivery, establish this activity directly. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Calcium binding by LDL-A repeats is structural. Reason: Each LDL-A module coordinates a calcium ion that is required for its fold and for ligand binding; endosomal calcium loss contributes to ligand release. This is a structural property supporting, not constituting, receptor function. Supporting Evidence: PMID:22091758 The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). |
| GO:0005515 protein binding | IPI PMID:10571240 Reelin is a ligand for lipoprotein receptors. | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:12221107 ARH is a modular adaptor protein that interacts with the LDL... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:17452316 Binding of proprotein convertase subtilisin/kexin type 9 to ... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:17461796 The cellular trafficking of the secretory proprotein convert... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:18250299 Molecular basis for LDL receptor recognition by PCSK9. | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:18753623 Structural requirements for PCSK9-mediated degradation of th... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:20030366 Decoding of lipoprotein-receptor interactions: properties of... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:20030366 Decoding of lipoprotein-receptor interactions: properties of... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:20223219 Mode of interaction between beta2GPI and lipoprotein recepto... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:22081141 Mechanistic implications for LDL receptor degradation from t... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:22509010 Atomic structure of the autosomal recessive hypercholesterol... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:23589850 LDL receptor and its family members serve as the cellular re... | MODIFY | Summary: The interactor is the VSV G glycoprotein, and LDLR is the major cell-entry receptor for vesicular stomatitis virus; virus receptor activity names that function. Reason: Unlike the other 'protein binding' rows here, this one has a specific GO function term available. The partner (UniProtKB:P03522) is the vesicular stomatitis virus glycoprotein G, and the cited study shows LDLR is the major entry port for VSV and VSV-G-pseudotyped vectors, with other LDLR-family members as alternative receptors. GO:0001618 virus receptor activity ('combining with a virus component and mediating entry of the virus into the cell') states exactly this. It is an exapted use of the lipoprotein-binding ectodomain by the virus, not a core physiological function of LDLR, so it is not promoted to a core function. Proposed replacements: virus receptor activity Supporting Evidence: PMID:23589850 Here we show that the LDL receptor (LDLR) serves as the major entry port of VSV and of VSV-G-pseudotyped lentiviral vectors in human and mouse cells, whereas other LDLR family members serve as alternative receptors. |
| GO:0005515 protein binding | IPI PMID:24447298 LDL receptor/lipoprotein recognition: endosomal weakening of... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:24447298 LDL receptor/lipoprotein recognition: endosomal weakening of... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:25613181 MMP-2 inhibits PCSK9-induced degradation of the LDL receptor... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:30443021 Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Int... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:30443021 Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Int... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005515 protein binding | IPI PMID:33420426 AXL is a candidate receptor for SARS-CoV-2 that promotes inf... | REMOVE | Summary: Co-immunoprecipitation with SARS-CoV-2 spike, in a paper whose own functional tests exclude LDLR as an entry receptor; no specific GO term applies. Reason: The partner (UniProtKB:P0DTC2) is the SARS-CoV-2 spike glycoprotein, so this row looks parallel to the VSV G row above, which is MODIFY to GO:0001618 virus receptor activity. It is not. The cited study is an AXL-receptor paper in which LDLR was one of three docking-predicted candidates; it pulled down spike in co-IP, but overexpressing it did not enhance pseudotype infection (only ACE2 and AXL did) and knocking it down did not reduce infection (only AXL did). The paper therefore reports a physical interaction while positively excluding the receptor function, so GO:0001618 would assert the opposite of what the evidence shows, and 'protein binding' says nothing about LDLR function. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:33420426 All three candidate receptors pulled down SARS-CoV-2 S in HEK293T cells PMID:33420426 Downregulation of AXL, but not ACE2, LDLR or EGFR, drastically reduced SARS |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative protein binding; partner-specific functions are captured elsewhere. Reason: The IPI evidence reports a physical interaction but 'protein binding' says nothing about LDLR function. The biologically important interactions (apoB-100/apoE ligand binding, PCSK9 and IDOL-mediated degradation, AP-2 adaptor recognition of the FxNPxY tail) are represented by more specific terms in this review. ARH (LDLRAP1) binding of the same tail motif has no specific GO function term, and is described in the gene description rather than annotated here. Removal does not mean the reported interaction is false. |
| GO:0005764 lysosome | IDA PMID:15166224 The modular adaptor protein ARH is required for low density ... | KEEP AS NON CORE | Summary: Lysosome localization reflects receptor degradation. Reason: LDLR is delivered to lysosomes when degraded after PCSK9 binding or IDOL ubiquitination; this is a fate rather than the site of function. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0005764 lysosome | IDA PMID:17461796 The cellular trafficking of the secretory proprotein convert... | KEEP AS NON CORE | Summary: Lysosome localization reflects receptor degradation. Reason: LDLR is delivered to lysosomes when degraded after PCSK9 binding or IDOL ubiquitination; this is a fate rather than the site of function. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0005764 lysosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Lysosome localization reflects receptor degradation. Reason: LDLR is delivered to lysosomes when degraded after PCSK9 binding or IDOL ubiquitination; this is a fate rather than the site of function. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0005768 endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Endosome localization of the internalized receptor. Reason: Correct general localization for the recycling receptor. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Early endosome is where LDL is released and LDLR sorted for recycling. Reason: After internalization LDLR reaches early endosomes, where acid pH drives ligand release and the closed conformation that permits recycling. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. PMID:15166224 In normal lymphocytes LDLRs were predominantly located in intracellular compartments, whereas in ARH-/- cells the receptors were almost exclusively on the plasma membrane. |
| GO:0005769 early endosome | IDA PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: Early endosome is where LDL is released and LDLR sorted for recycling. Reason: After internalization LDLR reaches early endosomes, where acid pH drives ligand release and the closed conformation that permits recycling. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. PMID:15166224 In normal lymphocytes LDLRs were predominantly located in intracellular compartments, whereas in ARH-/- cells the receptors were almost exclusively on the plasma membrane. |
| GO:0005769 early endosome | IDA PMID:17461796 The cellular trafficking of the secretory proprotein convert... | ACCEPT | Summary: Early endosome is where LDL is released and LDLR sorted for recycling. Reason: After internalization LDLR reaches early endosomes, where acid pH drives ligand release and the closed conformation that permits recycling. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. PMID:15166224 In normal lymphocytes LDLRs were predominantly located in intracellular compartments, whereas in ARH-/- cells the receptors were almost exclusively on the plasma membrane. |
| GO:0005769 early endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Early endosome is where LDL is released and LDLR sorted for recycling. Reason: After internalization LDLR reaches early endosomes, where acid pH drives ligand release and the closed conformation that permits recycling. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. PMID:15166224 In normal lymphocytes LDLRs were predominantly located in intracellular compartments, whereas in ARH-/- cells the receptors were almost exclusively on the plasma membrane. |
| GO:0005770 late endosome | IDA PMID:17461796 The cellular trafficking of the secretory proprotein convert... | KEEP AS NON CORE | Summary: Late endosome reflects degradation itineraries. Reason: LDLR reaches late endosomes mainly when diverted to degradation (for example by PCSK9). Supporting Evidence: PMID:17461796 In cells expressing the LDLR, PCSK9 sorted to post-ER compartments (i.e. endosomes in cell lines and Golgi apparatus in primary hepatocytes), where it colocalized with the LDLR. |
| GO:0005770 late endosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Late endosome reflects degradation itineraries. Reason: LDLR reaches late endosomes mainly when diverted to degradation (for example by PCSK9). Supporting Evidence: PMID:17461796 In cells expressing the LDLR, PCSK9 sorted to post-ER compartments (i.e. endosomes in cell lines and Golgi apparatus in primary hepatocytes), where it colocalized with the LDLR. |
| GO:0005794 Golgi apparatus | IDA PMID:17461796 The cellular trafficking of the secretory proprotein convert... | KEEP AS NON CORE | Summary: Golgi transit during biosynthesis. Reason: LDLR matures through the Golgi en route to the surface (class 2 FH alleles block this). Biosynthetic transit, not site of function. Supporting Evidence: PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. PMID:17461796 In cells expressing the LDLR, PCSK9 sorted to post-ER compartments (i.e. endosomes in cell lines and Golgi apparatus in primary hepatocytes), where it colocalized with the LDLR. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Golgi transit during biosynthesis. Reason: LDLR matures through the Golgi en route to the surface (class 2 FH alleles block this). Biosynthetic transit, not site of function. Supporting Evidence: PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. PMID:17461796 In cells expressing the LDLR, PCSK9 sorted to post-ER compartments (i.e. endosomes in cell lines and Golgi apparatus in primary hepatocytes), where it colocalized with the LDLR. |
| GO:0005886 plasma membrane | EXP PMID:17461796 The cellular trafficking of the secretory proprotein convert... | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | EXP PMID:19520913 LXR regulates cholesterol uptake through Idol-dependent ubiq... | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS PMID:2777800 Analysis of a recycling-impaired mutant of low density lipop... | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS PMID:6327078 Domain map of the LDL receptor: sequence homology with the e... | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-171087 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-171122 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-171141 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-174657 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-174706 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784729 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784734 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784735 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8863471 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: LDLR is a type I transmembrane plasma-membrane receptor. Reason: The receptor spans the plasma membrane once, with ligand-binding repeats outside and the internalization signal in the cytoplasmic tail. Supporting Evidence: PMID:6327078 The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0005905 clathrin-coated pit | IDA PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: Clustering in clathrin-coated pits is required for internalization. Reason: Receptor-ligand complexes cluster in clathrin-coated pits before internalization; this is defective in class 4 FH alleles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0005905 clathrin-coated pit | IDA PMID:6091915 The human LDL receptor: a cysteine-rich protein with multipl... | ACCEPT | Summary: Clustering in clathrin-coated pits is required for internalization. Reason: Receptor-ligand complexes cluster in clathrin-coated pits before internalization; this is defective in class 4 FH alleles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000044 | ACCEPT | Summary: Clustering in clathrin-coated pits is required for internalization. Reason: Receptor-ligand complexes cluster in clathrin-coated pits before internalization; this is defective in class 4 FH alleles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Too general; LDLR transports lipoproteins rather than metabolizing lipid. Reason: LDLR does not catalyse lipid metabolic reactions. Its role is uptake of lipoprotein particles, which is covered by receptor-mediated endocytosis and LDL clearance terms. |
| GO:0006629 lipid metabolic process | TAS PMID:10827173 Interactions of the low density lipoprotein receptor gene fa... | MARK AS OVER ANNOTATED | Summary: Too general; LDLR transports lipoproteins rather than metabolizing lipid. Reason: LDLR does not catalyse lipid metabolic reactions. Its role is uptake of lipoprotein particles, which is covered by receptor-mediated endocytosis and LDL clearance terms. |
| GO:0006629 lipid metabolic process | TAS PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | MARK AS OVER ANNOTATED | Summary: Too general; LDLR transports lipoproteins rather than metabolizing lipid. Reason: LDLR does not catalyse lipid metabolic reactions. Its role is uptake of lipoprotein particles, which is covered by receptor-mediated endocytosis and LDL clearance terms. |
| GO:0006897 endocytosis | TAS PMID:12671190 Integration of endocytosis and signal transduction by lipopr... | ACCEPT | Summary: Endocytosis is correct but general. Reason: Correct but less specific than receptor-mediated endocytosis, which is also annotated. Supporting Evidence: PMID:12671190 All LDLR family members are endocytic receptors that mediate the uptake of extracellular cargo into the cell |
| GO:0006898 receptor-mediated endocytosis | IEA GO_REF:0000120 | ACCEPT | Summary: Receptor-mediated endocytosis is the mechanism of LDLR function. Reason: LDLR internalizes bound ligand through clathrin-coated pits after recognition of its FxNPxY tail signal. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0006898 receptor-mediated endocytosis | ISS GO_REF:0000024 | ACCEPT | Summary: Receptor-mediated endocytosis is the mechanism of LDLR function. Reason: LDLR internalizes bound ligand through clathrin-coated pits after recognition of its FxNPxY tail signal. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0006898 receptor-mediated endocytosis | TAS PMID:24825898 A neuroprotective brain-penetrating endopeptidase fusion pro... | ACCEPT | Summary: Receptor-mediated endocytosis is the mechanism of LDLR function. Reason: LDLR internalizes bound ligand through clathrin-coated pits after recognition of its FxNPxY tail signal. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0006909 phagocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Phagocytosis is not an LDLR function. Reason: LDLR mediates clathrin-dependent receptor-mediated endocytosis of soluble lipoproteins, not phagocytosis of particles by phagocytes. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. |
| GO:0006909 phagocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Phagocytosis is not an LDLR function. Reason: LDLR mediates clathrin-dependent receptor-mediated endocytosis of soluble lipoproteins, not phagocytosis of particles by phagocytes. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. |
| GO:0007616 long-term memory | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Brain apoE-LDLR effects on memory in mice; non-core. Reason: Mouse genetic interaction data link LDLR-apoE binding to spatial memory retention. This is a downstream organism-level phenotype of receptor-mediated apoE uptake in brain, not a core function. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). |
| GO:0007616 long-term memory | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: Brain apoE-LDLR effects on memory in mice; non-core. Reason: Mouse genetic interaction data link LDLR-apoE binding to spatial memory retention. This is a downstream organism-level phenotype of receptor-mediated apoE uptake in brain, not a core function. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). |
| GO:0009897 external side of plasma membrane | IDA PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: External side of the plasma membrane carries the ligand-binding domain. Reason: The ligand-binding repeats face the extracellular side; LDLR is detected on the cell surface. Supporting Evidence: PMID:15166224 In normal lymphocytes LDLRs were predominantly located in intracellular compartments, whereas in ARH-/- cells the receptors were almost exclusively on the plasma membrane. |
| GO:0009986 cell surface | IDA PMID:17461796 The cellular trafficking of the secretory proprotein convert... | ACCEPT | Summary: Cell surface localization of functional receptor. Reason: Functional LDL receptors are displayed at the cell surface. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Cell surface localization of functional receptor. Reason: Functional LDL receptors are displayed at the cell surface. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0009986 cell surface | ISS GO_REF:0000024 | ACCEPT | Summary: Cell surface localization of functional receptor. Reason: Functional LDL receptors are displayed at the cell surface. Supporting Evidence: PMID:6091915 Transfection of simian COS cells with the human LDL receptor cDNA linked to the SV40 early promoter resulted in expression of functional cell surface receptors. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-171059 | ACCEPT | Summary: Endosome membrane localization of the internalized receptor. Reason: LDLR is a transmembrane cargo of endosomes during its recycling itinerary. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-171087 | ACCEPT | Summary: Endosome membrane localization of the internalized receptor. Reason: LDLR is a transmembrane cargo of endosomes during its recycling itinerary. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-171106 | ACCEPT | Summary: Endosome membrane localization of the internalized receptor. Reason: LDLR is a transmembrane cargo of endosomes during its recycling itinerary. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Indirect gene-expression phenotype. Reason: Altered gene expression in Ldlr-deficient mice follows from sterol changes (SREBP feedback), not from LDLR activity. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Indirect gene-expression phenotype. Reason: As above; indirect effect of altered cellular sterol supply. |
| GO:0010867 positive regulation of triglyceride biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Indirect knockout phenotype. Reason: Rodent-derived annotation reflecting altered lipid flux in Ldlr-deficient animals; LDLR does not regulate triglyceride synthesis directly. |
| GO:0010867 positive regulation of triglyceride biosynthetic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Indirect knockout phenotype. Reason: Rodent-derived annotation reflecting altered lipid flux in Ldlr-deficient animals; LDLR does not regulate triglyceride synthesis directly. |
| GO:0010899 regulation of phosphatidylcholine catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Indirect knockout phenotype. Reason: Rodent-derived; no evidence that LDLR regulates phosphatidylcholine catabolism directly. |
| GO:0010899 regulation of phosphatidylcholine catabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Indirect knockout phenotype. Reason: Rodent-derived; no evidence that LDLR regulates phosphatidylcholine catabolism directly. |
| GO:0010989 negative regulation of low-density lipoprotein particle clearance | IDA PMID:17452316 Binding of proprotein convertase subtilisin/kexin type 9 to ... | MARK AS OVER ANNOTATED | Summary: LDLR mediates LDL clearance; PCSK9 is the negative regulator. Reason: The cited work shows PCSK9 reduces LDL clearance by degrading LDLR. LDLR itself performs clearance (GO:0034383); annotating it to negative regulation of clearance reverses its role. Supporting Evidence: PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. |
| GO:0015914 phospholipid transport | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Phospholipids enter with LDL particles; not a distinct transport function. Reason: Lipoprotein phospholipid is internalized together with the particle; LDLR is not a phospholipid transporter. |
| GO:0015914 phospholipid transport | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Phospholipids enter with LDL particles; not a distinct transport function. Reason: Lipoprotein phospholipid is internalized together with the particle; LDLR is not a phospholipid transporter. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Membrane, from a proteomics survey. Reason: Correct but uninformative; more specific plasma membrane annotations exist. |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Basolateral surface of polarized cells. Reason: In polarized epithelia and hepatocytes LDLR is targeted to the basolateral (sinusoidal) surface; plausible but transferred from orthologs. |
| GO:0016323 basolateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Basolateral surface of polarized cells. Reason: In polarized epithelia and hepatocytes LDLR is targeted to the basolateral (sinusoidal) surface; plausible but transferred from orthologs. |
| GO:0030169 low-density lipoprotein particle binding | IEA GO_REF:0000120 | ACCEPT | Summary: LDL particle binding by the ligand-binding repeats is the first step of receptor function. Reason: LDLR binds apoB-100 on LDL through its cysteine-rich LDL-A repeats; FH class 3 alleles reach the cell surface but fail to bind LDL. This is the binding component of the core receptor activity. Supporting Evidence: PMID:6299582 The other three mutations specify precursors (100, 120, and 170 kd) that undergo a normal 40 kd increase in molecular weight and reach the surface, but do not bind LDL normally. PMID:22091758 The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). |
| GO:0030169 low-density lipoprotein particle binding | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: LDL particle binding by the ligand-binding repeats is the first step of receptor function. Reason: LDLR binds apoB-100 on LDL through its cysteine-rich LDL-A repeats; FH class 3 alleles reach the cell surface but fail to bind LDL. This is the binding component of the core receptor activity. Supporting Evidence: PMID:6299582 The other three mutations specify precursors (100, 120, and 170 kd) that undergo a normal 40 kd increase in molecular weight and reach the surface, but do not bind LDL normally. PMID:22091758 The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). |
| GO:0030229 very-low-density lipoprotein particle receptor activity | IDA PMID:8626535 Human apolipoprotein E receptor 2. A novel lipoprotein recep... | ACCEPT | Summary: VLDL receptor activity used as comparator in an apoER2 study. Reason: LDLR binds apoE-rich VLDL and beta-VLDL; accepted as a genuine secondary core activity. Supporting Evidence: PMID:8626535 The new receptor consists of five functional domains resembling the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) receptors. PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. |
| GO:0030229 very-low-density lipoprotein particle receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: LDLR also binds and internalizes apoE-containing VLDL and remnants. Reason: LDLR binds apoE-rich beta-VLDL and apoE-lipid complexes in addition to LDL, so VLDL receptor activity is a genuine, secondary core activity contributing to remnant clearance; LDL uptake remains the defining physiological role. Supporting Evidence: PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). |
| GO:0030299 intestinal cholesterol absorption | IMP PMID:17142622 Genetic causes of familial hypercholesterolaemia in patients... | MARK AS OVER ANNOTATED | Summary: Intestinal cholesterol absorption is not supported by the cited genetics study. Reason: The cited UK FH cohort study reports mutation frequencies and coronary risk; the cached full text contains no intestinal absorption data. Intestinal sterol absorption is mediated by NPC1L1 and ABCG5/8, not LDLR. Supporting Evidence: PMID:17142622 To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9) |
| GO:0030301 cholesterol transport | IMP PMID:17142622 Genetic causes of familial hypercholesterolaemia in patients... | ACCEPT | Summary: Cholesterol transport is a correct general process. Reason: LDLR moves LDL-borne cholesterol into cells; consistent with the more specific receptor-mediated endocytosis term. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0030301 cholesterol transport | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: Cholesterol transport is a correct general process. Reason: LDLR moves LDL-borne cholesterol into cells; consistent with the more specific receptor-mediated endocytosis term. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-171059 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: LDLR is internalized in clathrin-coated endocytic vesicles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-171141 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: LDLR is internalized in clathrin-coated endocytic vesicles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-174706 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: LDLR is internalized in clathrin-coated endocytic vesicles. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. |
| GO:0032050 clathrin heavy chain binding | IEA GO_REF:0000117 | MODIFY | Summary: The LDLR tail binds clathrin adaptors (AP-2, ARH), not clathrin heavy chain directly. Reason: The FDNPVY internalization signal in the LDLR cytoplasmic tail is recognized by the mu2 subunit of AP-2 and by ARH, which in turn recruit clathrin. The cited study shows binding to AP-2 mu2, so AP-2 adaptor complex binding is the accurate term. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0032050 clathrin heavy chain binding | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | MODIFY | Summary: The LDLR tail binds clathrin adaptors (AP-2, ARH), not clathrin heavy chain directly. Reason: The FDNPVY internalization signal in the LDLR cytoplasmic tail is recognized by the mu2 subunit of AP-2 and by ARH, which in turn recruit clathrin. The cited study shows binding to AP-2 mu2, so AP-2 adaptor complex binding is the accurate term. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12121421 The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. |
| GO:0034381 plasma lipoprotein particle clearance | IEA GO_REF:0000107 | ACCEPT | Summary: Plasma lipoprotein particle clearance is a correct parent process. Reason: LDLR clears LDL and apoE-containing remnant lipoproteins from plasma; the more specific LDL particle clearance is also annotated. Supporting Evidence: PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. |
| GO:0034381 plasma lipoprotein particle clearance | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma lipoprotein particle clearance is a correct parent process. Reason: LDLR clears LDL and apoE-containing remnant lipoproteins from plasma; the more specific LDL particle clearance is also annotated. Supporting Evidence: PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. |
| GO:0034381 plasma lipoprotein particle clearance | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: Plasma lipoprotein particle clearance is a correct parent process. Reason: LDLR clears LDL and apoE-containing remnant lipoproteins from plasma; the more specific LDL particle clearance is also annotated. Supporting Evidence: PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. |
| GO:0034383 low-density lipoprotein particle clearance | IEA GO_REF:0000117 | ACCEPT | Summary: Core process: hepatic LDLR is the main route of plasma LDL clearance. Reason: Loss-of-function LDLR alleles cause familial hypercholesterolemia because plasma LDL is not cleared. This is the organism-level process directly carried out by the receptor. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0034383 low-density lipoprotein particle clearance | IMP PMID:17142622 Genetic causes of familial hypercholesterolaemia in patients... | ACCEPT | Summary: Core process: hepatic LDLR is the main route of plasma LDL clearance. Reason: Loss-of-function LDLR alleles cause familial hypercholesterolemia because plasma LDL is not cleared. This is the organism-level process directly carried out by the receptor. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0034383 low-density lipoprotein particle clearance | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: Core process: hepatic LDLR is the main route of plasma LDL clearance. Reason: Loss-of-function LDLR alleles cause familial hypercholesterolemia because plasma LDL is not cleared. This is the organism-level process directly carried out by the receptor. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0034384 high-density lipoprotein particle clearance | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: HDL clearance is not an established LDLR function. Reason: Transferred from rodent data; LDLR can bind apoE-rich HDL subclasses, but HDL clearance is chiefly SR-BI dependent. Not a core LDLR function. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784729 | KEEP AS NON CORE | Summary: Endolysosome membrane reflects degradation. Reason: As for lysosome; degradative compartment. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784738 | KEEP AS NON CORE | Summary: Endolysosome membrane reflects degradation. Reason: As for lysosome; degradative compartment. Supporting Evidence: PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0036477 somatodendritic compartment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal somatodendritic localization; non-core. Reason: LDLR is expressed in neurons and glia, but this ortholog-transferred location is peripheral to its hepatic role. |
| GO:0042632 cholesterol homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042632 cholesterol homeostasis | IEA GO_REF:0000117 | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042632 cholesterol homeostasis | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042632 cholesterol homeostasis | IMP PMID:17142622 Genetic causes of familial hypercholesterolaemia in patients... | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042632 cholesterol homeostasis | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042632 cholesterol homeostasis | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: LDLR is a central effector of whole-body cholesterol homeostasis. Reason: Hepatic LDLR abundance sets plasma LDL cholesterol levels and is the target of SREBP, PCSK9 and IDOL regulation; its loss causes FH. Supporting Evidence: PMID:19520913 an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. PMID:17452316 As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded. |
| GO:0042802 identical protein binding | IPI PMID:26526611 The closed conformation of the LDL receptor is destabilized ... | MARK AS OVER ANNOTATED | Summary: Intramolecular module interaction, not homo-oligomerization. Reason: The cited study measured binding between the LR4-5 ligand-binding modules and the beta-propeller of the same receptor (the closed endosomal conformation). That is an intramolecular rearrangement, which 'identical protein binding' does not describe well. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0043235 signaling receptor complex | IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | UNDECIDED | Summary: Signaling receptor complex is not supported in the cached text. Reason: The cited PX-FERM structural study concerns SNX17 recognition of NPxY sorting motifs in cargo including LDLR-family members; the cached text does not describe LDLR in a signaling receptor complex, and LDLR is an endocytic rather than signaling receptor. The curator's full-text basis could not be verified. Supporting Evidence: PMID:23382219 the LDLR receptor is recognized by ARH for internalization |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Apical localization is not characteristic of LDLR. Reason: LDLR carries basolateral sorting information; apical localization is transferred from orthologs and is not a characteristic site of function. |
| GO:0045177 apical part of cell | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Apical localization is not characteristic of LDLR. Reason: LDLR carries basolateral sorting information; apical localization is transferred from orthologs and is not a characteristic site of function. |
| GO:0048844 artery morphogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Artery morphogenesis is an indirect knockout phenotype. Reason: Arterial lesions in Ldlr-deficient mice are atherosclerosis secondary to hypercholesterolemia, not a developmental role. |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Inflammation is an indirect knockout phenotype. Reason: Inflammatory changes in Ldlr-deficient animals are secondary to hyperlipidemia. |
| GO:0051241 negative regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Vague organismal regulation term; indirect. Reason: Uninformative, phenotype-derived annotation. |
| GO:0051246 regulation of protein metabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Regulation of brain apoE levels via uptake; non-core. Reason: LDLR lowers brain apoE protein levels by internalizing it; this is a consequence of receptor-mediated endocytosis. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). PMID:20005821 To test our hypothesis, we created several transgenic mice that overexpress LDLR in the brain and found that apoE levels in these mice decreased by 50%-90%. |
| GO:0051246 regulation of protein metabolic process | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: Regulation of brain apoE levels via uptake; non-core. Reason: LDLR lowers brain apoE protein levels by internalizing it; this is a consequence of receptor-mediated endocytosis. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). PMID:20005821 To test our hypothesis, we created several transgenic mice that overexpress LDLR in the brain and found that apoE levels in these mice decreased by 50%-90%. |
| GO:0051248 negative regulation of protein metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lowering of apoE protein levels via uptake; non-core. Reason: Brain LDLR overexpression lowers apoE protein levels through uptake and degradation; an indirect consequence of endocytosis. Supporting Evidence: PMID:20005821 To test our hypothesis, we created several transgenic mice that overexpress LDLR in the brain and found that apoE levels in these mice decreased by 50%-90%. |
| GO:0051248 negative regulation of protein metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lowering of apoE protein levels via uptake; non-core. Reason: Brain LDLR overexpression lowers apoE protein levels through uptake and degradation; an indirect consequence of endocytosis. Supporting Evidence: PMID:20005821 To test our hypothesis, we created several transgenic mice that overexpress LDLR in the brain and found that apoE levels in these mice decreased by 50%-90%. |
| GO:0060090 molecular adaptor activity | EXP PMID:22091758 The structure, dynamics, and binding of the LA45 module pair... | MARK AS OVER ANNOTATED | Summary: LDLR is a cargo receptor, not a molecular adaptor. Reason: The cited NMR and binding study characterizes ligand binding by the LA4-LA5 modules. Binding a ligand and carrying it into the cell is receptor activity (GO:0005041), not bridging two other molecules as an adaptor. Supporting Evidence: PMID:22091758 The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). |
| GO:0061771 response to caloric restriction | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Response to caloric restriction is an indirect phenotype. Reason: The cited mouse study concerns apoE isoform-LDLR interaction and memory; any change under dietary restriction is a phenotype, not an LDLR activity. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). |
| GO:0061771 response to caloric restriction | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | MARK AS OVER ANNOTATED | Summary: Response to caloric restriction is an indirect phenotype. Reason: The cited mouse study concerns apoE isoform-LDLR interaction and memory; any change under dietary restriction is a phenotype, not an LDLR activity. Supporting Evidence: PMID:24412220 The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). |
| GO:0061889 negative regulation of astrocyte activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Reduced astrocyte activation is an indirect phenotype. Reason: Attenuated neuroinflammation in LDLR-overexpressing mice is downstream of reduced amyloid load, not an LDLR regulatory activity. |
| GO:0061889 negative regulation of astrocyte activation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Reduced astrocyte activation is an indirect phenotype. Reason: Attenuated neuroinflammation in LDLR-overexpressing mice is downstream of reduced amyloid load, not an LDLR regulatory activity. |
| GO:0070508 cholesterol import | IEA GO_REF:0000120 | ACCEPT | Summary: Cholesterol import via LDL uptake. Reason: LDL uptake through LDLR is the main route by which cells import exogenous cholesterol. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0070508 cholesterol import | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: Cholesterol import via LDL uptake. Reason: LDL uptake through LDLR is the main route by which cells import exogenous cholesterol. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0070508 cholesterol import | ISS GO_REF:0000024 | ACCEPT | Summary: Cholesterol import via LDL uptake. Reason: LDL uptake through LDLR is the main route by which cells import exogenous cholesterol. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0071398 cellular response to fatty acid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Indirect phenotype. Reason: Rodent-derived; LDLR expression responds to fatty acids via sterol regulation, but this is not an LDLR activity. |
| GO:0071404 cellular response to low-density lipoprotein particle stimulus | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | MARK AS OVER ANNOTATED | Summary: Response to LDL stimulus is not what the 1983 study shows. Reason: The FH fibroblast study measured synthesis, transport and LDL binding of the receptor itself. LDLR binds LDL as its ligand; it is not responding to LDL as a signal. Supporting Evidence: PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0071813 lipoprotein particle binding | IBA GO_REF:0000033 | ACCEPT | Summary: Lipoprotein particle binding is a correct, general parent of the core binding activity. Reason: LDLR binds apoB-100- and apoE-containing lipoprotein particles; the IBA is consistent with the family-wide ligand-binding function. Supporting Evidence: PMID:22091758 The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). PMID:2777800 This mutant receptor could not bind LDL, but could bind other ligands for the LDL receptor, beta-migrating very low density lipoprotein, and the apolipoprotein E-lipid complex. |
| GO:0090118 receptor-mediated endocytosis involved in cholesterol transport | IBA GO_REF:0000033 | ACCEPT | Summary: Core process: receptor-mediated endocytosis of LDL delivers cholesterol to cells. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. This is the most precise process term for the receptor's role. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0090118 receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:6299582 The LDL receptor locus in familial hypercholesterolemia: mul... | ACCEPT | Summary: Core process: receptor-mediated endocytosis of LDL delivers cholesterol to cells. Reason: LDLR is the hepatocyte cell-surface receptor that captures apoB-100-containing LDL (and apoE-containing lipoproteins) and carries it into the cell by clathrin-mediated endocytosis. This is the most precise process term for the receptor's role. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. PMID:6299582 The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. |
| GO:0090181 regulation of cholesterol metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cholesterol uptake feeds back on sterol synthesis; indirect. Reason: LDL cholesterol delivered by LDLR suppresses SREBP-driven cholesterol synthesis, so LDLR influences cholesterol metabolism indirectly through its uptake function. Supporting Evidence: file:human/LDLR/LDLR-uniprot.txt Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. |
| GO:0097242 amyloid-beta clearance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Brain amyloid-beta clearance by LDLR; non-core. Reason: LDLR overexpression in mouse brain enhanced extracellular amyloid-beta clearance; non-core relative to plasma LDL clearance. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:0097242 amyloid-beta clearance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Brain amyloid-beta clearance by LDLR; non-core. Reason: LDLR overexpression in mouse brain enhanced extracellular amyloid-beta clearance; non-core relative to plasma LDL clearance. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:0097443 sorting endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sorting endosome. Reason: LDLR passes through sorting endosomes; correct but an itinerary detail. Supporting Evidence: PMID:26526611 In the endosomes, it adopts a closed conformation important for recycling, by interaction of two modules of the ligand binding domain (LR4-5) and a Ξ²-propeller motif. |
| GO:0150094 amyloid-beta clearance by cellular catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Specific Abeta catabolic clearance; non-core. Reason: Receptor-mediated uptake leading to lysosomal degradation of amyloid-beta, reported in rodents; non-core. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:0150094 amyloid-beta clearance by cellular catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Specific Abeta catabolic clearance; non-core. Reason: Receptor-mediated uptake leading to lysosomal degradation of amyloid-beta, reported in rodents; non-core. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:1903979 negative regulation of microglial cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Reduced microglial activation is an indirect phenotype. Reason: As for astrocyte activation, attenuated microgliosis is downstream of reduced amyloid load. |
| GO:1903979 negative regulation of microglial cell activation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Reduced microglial activation is an indirect phenotype. Reason: As for astrocyte activation, attenuated microgliosis is downstream of reduced amyloid load. |
| GO:1905167 positive regulation of lysosomal protein catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Lysosomal delivery of internalized cargo is not regulation of catabolism. Reason: Delivery of ligands to lysosomes after endocytosis is part of the receptor's transport itinerary; it does not make LDLR a regulator of lysosomal protein catabolism. Supporting Evidence: PMID:10827173 Traditionally, they had been regarded as mere cargo receptors that promote the endocytosis and lysosomal delivery of these ligands. |
| GO:1905167 positive regulation of lysosomal protein catabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Lysosomal delivery of internalized cargo is not regulation of catabolism. Reason: Delivery of ligands to lysosomes after endocytosis is part of the receptor's transport itinerary; it does not make LDLR a regulator of lysosomal protein catabolism. Supporting Evidence: PMID:10827173 Traditionally, they had been regarded as mere cargo receptors that promote the endocytosis and lysosomal delivery of these ligands. |
| GO:1905907 negative regulation of amyloid fibril formation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Reduced amyloid aggregation is an indirect consequence of clearance. Reason: LDLR does not act on fibril formation itself; reduced amyloid deposition in transgenic mice follows from increased clearance and lower apoE. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:1905907 negative regulation of amyloid fibril formation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Reduced amyloid aggregation is an indirect consequence of clearance. Reason: LDLR does not act on fibril formation itself; reduced amyloid deposition in transgenic mice follows from increased clearance and lower apoE. Supporting Evidence: PMID:20005821 LDLR overexpression dramatically reduced A beta aggregation and enhanced A beta clearance from the brain extracellular space. |
| GO:1990666 PCSK9-LDLR complex | IDA PMID:22081141 Mechanistic implications for LDL receptor degradation from t... | KEEP AS NON CORE | Summary: LDLR is a subunit of the PCSK9-LDLR complex. Reason: The PCSK9-LDLR complex is structurally defined, but it is a regulatory complex that targets LDLR for degradation, not the functional unit of LDL uptake. Supporting Evidence: PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. |
| GO:1990666 PCSK9-LDLR complex | IDA PMID:22848640 Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-... | KEEP AS NON CORE | Summary: LDLR is a subunit of the PCSK9-LDLR complex. Reason: The PCSK9-LDLR complex is structurally defined, but it is a regulatory complex that targets LDLR for degradation, not the functional unit of LDL uptake. Supporting Evidence: PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. |
| GO:1990666 PCSK9-LDLR complex | IPI PMID:22081141 Mechanistic implications for LDL receptor degradation from t... | KEEP AS NON CORE | Summary: LDLR is a subunit of the PCSK9-LDLR complex. Reason: The PCSK9-LDLR complex is structurally defined, but it is a regulatory complex that targets LDLR for degradation, not the functional unit of LDL uptake. Supporting Evidence: PMID:22081141 We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. PMID:17452316 Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)