CIDeRplusGeneral Information:
| Id: | 7,255 |
| Diseases: |
Alzheimer disease
- [OMIM]
Metabolic |
| Mammalia | |
| review | |
| Reference: | Phillips MC(2014) Apolipoprotein E isoforms and lipoprotein metabolism IUBMB Life 66: 616-623 [PMID: 25328986] |
Interaction Information:
| Comment | APOE3: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. This result occurs because apoE3 possesses both the requisite lipid-binding ability and affinity for the low density lipoprotein receptor (LDLR) to mediate appropriate lipolytic processing and endocytosis of TG-rich lipoprotein remnant particles. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71370 |
gene/protein mutant increases_activity of |
| Comment | APOE2: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71374 |
gene/protein mutant decreases_activity of |
| Comment | APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71375 |
gene/protein mutant increases_activity of phenotype |
| Comment | APOE3: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. This result occurs because apoE3 possesses both the requisite lipid-binding ability and affinity for the low density lipoprotein receptor (LDLR) to mediate appropriate lipolytic processing and endocytosis of TG-rich lipoprotein remnant particles. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71385 |
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| Comment | APOE2: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71386 |
gene/protein mutant increases_activity of phenotype |
| Comment | APOE2: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71387 |
gene/protein mutant increases_activity of disease Hyperlipoproteinemia, type III |
| Comment | APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71388 |
gene/protein mutant affects_activity of |
| Comment | APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71391 |
gene/protein mutant increases_activity of process |
| Comment | APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71392 |
gene/protein mutant increases_activity of |
| Comment | ApoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). |
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Formal Description Interaction-ID: 71394 |
gene/protein mutant increases_activity of phenotype alatered VLDL lipolytic processing |
| Comment | ApoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). |
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Formal Description Interaction-ID: 71403 |
gene/protein mutant increases_activity of phenotype increased pro-atherogenic lipoprotein-cholesterol distribution |
| Comment | APOE2: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71414 |
gene/protein mutant decreases_activity of |
| Comment | APOE3: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. This result occurs because apoE3 possesses both the requisite lipid-binding ability and affinity for the low density lipoprotein receptor (LDLR) to mediate appropriate lipolytic processing and endocytosis of TG-rich lipoprotein remnant particles. ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 71415 |
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| Comment | In mice expressing either human apoE3 or apoE4 expression of apoE4 is associated with higher VLDL-cholesterol and incidence of atherosclerosis. |
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Formal Description Interaction-ID: 71423 |
gene/protein mutant increases_activity of |
| Comment | In mice expressing either human apoE3 or apoE4 expression of apoE4 is associated with higher VLDL-cholesterol and incidence of atherosclerosis. |
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Formal Description Interaction-ID: 71430 |
gene/protein mutant increases_activity of |
| Comment | Hypercholesterolemia is associated with apoE4. |
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Formal Description Interaction-ID: 71431 |
gene/protein mutant increases_activity of phenotype |
| Comment | ApoE4 binds much better than apoE3 to VLDL but somewhat less well than apoE3 to HDL. |
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Formal Description Interaction-ID: 71436 |
gene/protein mutant decreases_activity of |
| Comment | ApoE4 binds more to VLDL because of its higher lipid affinity leading to inhibition of lipolysis (probably because of displacement of apoC-II) so that, at the same apoE expression level of ApoE3 and ApoE4, progression down the lipolysis cascade is relatively limited in the case of apoE4. |
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Formal Description Interaction-ID: 71448 |
gene/protein mutant decreases_activity of process |
| Comment | ApoE4 binds more to VLDL because of its higher lipid affinity leading to inhibition of lipolysis (probably because of displacement of apoC-II) so that, at the same apoE expression level of ApoE3 and ApoE4, progression down the lipolysis cascade is relatively limited in the case of apoE4. |
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Formal Description Interaction-ID: 111429 |
gene/protein mutant interacts (colocalizes) with complex/PPI VLDL |
| Comment | Hypercholesterolemia is associated with apoE4. |
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Formal Description Interaction-ID: 113458 |
gene/protein mutant decreases_activity of process |
| Comment | AapoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / HDL-cholesterol ratio). Hypercholesterolemia is also associated with ApoE4. |
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Formal Description Interaction-ID: 113461 |
phenotype decreases_activity of process |
| Comment | ApoE4 binds more to VLDL because of its higher lipid affinity leading to inhibition of lipolysis (probably because of displacement of apoC-II) so that, at the same apoE expression level of ApoE3 and ApoE4, progression down the lipolysis cascade is relatively limited in the case of apoE4. |
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Formal Description Interaction-ID: 114524 |
gene/protein mutant decreases_activity of process VLDL lipid catabolic process |
| Comment | APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker. |
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Formal Description Interaction-ID: 114525 |
gene/protein mutant decreases_activity of |