# APOE Gene: Properties and Relationships in the ProKN Knowledge Graph

👤 **User**
@prokn: Find properties and relationships associated with the APOE gene

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🧠 **Assistant**

The ProKN knowledge graph (Protein Knowledge Network, UniProt-based) contains rich data on the APOE gene and its protein product Apolipoprotein E (UniProt P02649). Here is a comprehensive breakdown of the properties and relationships found.

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## Gene / Protein Identity

| Property | Value |
|---|---|
| Gene symbol | APOE |
| Protein name | Apolipoprotein E |
| UniProt accession | P02649 |
| Mnemonic | APOE_HUMAN |
| Organism | *Homo sapiens* |
| Source | UniProtKB (reviewed / Swiss-Prot) |

Mouse orthologs (Mus musculus) are also present:

| UniProt accession | Length |
|---|---|
| A0A1B0GX15 | 231 aa |
| G3UWN5 | 232 aa |
| G3UZM8 | 146 aa |
| G3UWW2 | 71 aa |

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## Lipoprotein Particle Associations (`part of`)

APOE is a structural component of all major lipoprotein particle classes:

- Chylomicron
- Chylomicron remnant
- Very-low-density lipoprotein (VLDL) particle
- Low-density lipoprotein (LDL) particle
- Intermediate-density lipoprotein (IDL) particle
- High-density lipoprotein (HDL) particle
- Discoidal high-density lipoprotein particle
- Lipoprotein particle (generic)

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## Molecular Functions (`enables`)

| Function | GO Term |
|---|---|
| Amyloid-beta binding | GO:0001540 |
| Signaling receptor binding | GO:0005102 |
| Structural molecule activity | GO:0005198 |
| Lipid transporter activity | GO:0005319 |
| Protein binding | GO:0005515 |
| Phospholipid binding | GO:0005543 |
| Heparin binding | GO:0008201 |
| Lipid binding | GO:0008289 |
| Antioxidant activity | GO:0016209 |
| Enzyme binding | GO:0019899 |
| Identical protein binding | GO:0042802 |
| Protein homodimerization activity | GO:0042803 |
| Heparan sulfate proteoglycan binding | GO:0043395 |
| Protein-containing complex binding | GO:0044877 |
| Metal chelating activity | GO:0046911 |
| Protein dimerization activity | GO:0046983 |
| Receptor ligand activity | GO:0048018 |
| Tau protein binding | GO:0048156 |
| LDL particle receptor binding | GO:0050750 |
| Phosphatidylcholine-sterol O-acyltransferase activator activity | GO:0060228 |
| VLDL particle receptor binding | GO:0070326 |
| Lipoprotein particle binding | GO:0071813 |
| Cholesterol transfer activity | GO:0120020 |

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## Biological Processes (`involved in` / `acts upstream of or within`)

**Lipid & cholesterol metabolism**
- Lipid metabolic process (GO:0006629)
- Fatty acid metabolic process (GO:0006631)
- Cholesterol catabolic process (GO:0006707)
- Cholesterol metabolic process (GO:0008203)
- Cholesterol homeostasis (GO:0042632)
- Cholesterol efflux (GO:0033344)
- Positive regulation of cholesterol efflux (GO:0010875)
- Negative regulation of cholesterol efflux (GO:0090370)
- Negative regulation of cholesterol biosynthetic process (GO:0045541)
- Reverse cholesterol transport (GO:0043691)
- Triglyceride metabolic process (GO:0006641)
- Triglyceride homeostasis (GO:0070328)
- Negative regulation of triglyceride metabolic process (GO:0090209)
- Long-chain fatty acid transport (GO:0015909)
- Fatty acid homeostasis (GO:0055089)
- Lipid transport (GO:0006869)
- Lipid transport involved in lipid storage (GO:0010877)
- Lipid homeostasis (GO:0055088)
- Lipoprotein metabolic process (GO:0042157)
- Lipoprotein biosynthetic process (GO:0042158)
- Lipoprotein catabolic process (GO:0042159)
- Lipoprotein biosynthetic process (GO:0042158)
- Phospholipid efflux (GO:0033700)
- Steroid metabolic process (GO:0008202)

**Lipoprotein particle clearance & remodeling**
- Chylomicron remnant clearance (GO:0034382)
- High-density lipoprotein particle clearance (GO:0034384)
- Very-low-density lipoprotein particle clearance (GO:0034447)
- Triglyceride-rich lipoprotein particle clearance (GO:0071830)
- Intermediate-density lipoprotein particle clearance (GO:0071831)
- VLDL particle remodeling (GO:0034372)
- LDL particle remodeling (GO:0034374)
- HDL particle remodeling (GO:0034375)
- High-density lipoprotein particle assembly (GO:0034380)

**Neurological processes**
- Amyloid precursor protein metabolic process (GO:0042982)
- Amyloid fiber formation *(Reactome)*
- Dendritic spine development — positive (GO:0060999) and negative (GO:0061000) regulation
- Dendritic spine maintenance — positive (GO:1902952) and negative (GO:1902951) regulation
- Neuron projection development (GO:0031175)
- Positive/negative regulation of neuron projection development (GO:0010976 / GO:0010977)
- Long-term memory (GO:0007616)
- Regulation of neuronal synaptic plasticity (GO:0048168)
- Regulation of synapse organization (GO:0050807)
- Regulation of axon extension (GO:0030516)
- Cholinergic synaptic transmission (GO:0007271)
- Locomotory exploration behavior (GO:0035641)

**Cardiovascular & vascular**
- Blood vessel development (GO:0001568)
- Artery development (GO:0060840)
- Artery morphogenesis (GO:0048844)
- Circulatory system development (GO:0072359)
- Vasodilation (GO:0042311)
- Negative regulation of endothelial cell proliferation (GO:0001937)
- Negative regulation of endothelial cell migration (GO:0010596)
- Negative regulation of blood vessel endothelial cell migration (GO:0043537)
- Negative regulation of blood coagulation (GO:0030195)
- Negative regulation of platelet activation (GO:0010544)
- Negative regulation of platelet-derived growth factor receptor signaling (GO:0010642)
- Nitric oxide-cGMP-mediated signaling (GO:0038060)
- Positive regulation of nitric oxide biosynthetic process (GO:0045429)

**Signaling & regulation**
- Signal transduction (GO:0007165)
- G protein-coupled receptor signaling pathway (GO:0007186)
- Regulation of gene expression (GO:0010468)
- Positive/negative regulation of gene expression (GO:0045893 / GO:0010629)
- Regulation of insulin-like growth factor transport *(Reactome)*
- Positive regulation of ERK1 and ERK2 cascade (GO:0070374)
- Negative regulation of MAPK cascade (GO:0043409)
- Regulation of Cdc42 protein signal transduction (GO:0032489)
- Negative regulation of canonical Wnt signaling pathway (GO:0090090)
- Positive regulation of membrane protein ectodomain proteolysis (GO:0051044)

**Immune & stress response**
- Response to reactive oxygen species (GO:0000302)
- Response to oxidative stress (GO:0006979)
- Regulation of innate immune response (GO:0045088)
- Negative regulation of inflammatory response (GO:0050728)
- Response to caloric restriction (GO:0061771)
- Response to dietary excess (GO:0002021)

**Other processes**
- Receptor-mediated endocytosis (GO:0006898)
- Positive regulation of endocytosis (GO:0045807)
- Virion assembly (GO:0019068)
- Host-mediated activation of viral process (GO:0044794)
- Apoptotic process regulation (GO:0042981)
- Regulation of proteasomal protein catabolic process (GO:0061136)
- Regulation of protein metabolic process (GO:0051246 / GO:0051248)
- Regulation of protein-containing complex assembly (GO:0043254)
- Melanosome organization (GO:0032438)
- Maintenance of location in cell (GO:0051651)
- Cellular response to lipoprotein particle stimulus (GO:0071402)
- Intracellular calcium ion homeostasis (GO:0006874) / Calcium ion homeostasis (GO:0055074)
- Protein import (GO:0017038)
- Intracellular transport (GO:0046907)
- Cytoskeleton organization (GO:0007010)

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## Reactome Pathways (`participates in`)

| Pathway | Reactome ID |
|---|---|
| Chylomicron assembly | R-HSA-8963888 |
| Chylomicron remodeling | R-HSA-8963901 |
| Chylomicron clearance | R-HSA-8964026 |
| HDL remodeling | R-HSA-8964058 |
| Amyloid fiber formation | R-HSA-977225 |
| Retinoid metabolism and transport | R-HSA-975634 |
| Post-translational protein phosphorylation | R-HSA-8957275 |
| Regulation of IGF transport and uptake by IGFBPs | R-HSA-381426 |
| NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux | R-HSA-9029569 |
| Scavenging by Class A Receptors | R-HSA-3000480 |
| Nuclear signaling by ERBB4 | R-HSA-1251985 |
| Transcriptional regulation by AP-2 (TFAP2) family | R-HSA-8864260 |

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## Disease Associations (`associated_with`)

| Disease | OMIM ID |
|---|---|
| Broad-Betalipoproteinemia (HLPP3) | OMIM:617347 |
| Apolipoprotein E, Deficiency or Defect of | OMIM:617347 |
| Lipoprotein Glomerulopathy | OMIM:611771 |
| SBHD disease | OMIM:269600 |

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## Protein–Protein Interactions (`interacts with`)

| Interacting protein | UniProt |
|---|---|
| Prolow-density lipoprotein receptor-related protein 1 (LRP1) | Q07954 |
| Low-density lipoprotein receptor-related protein 8 (LRP8) | Q14114 |
| Sortilin | Q99523 |
| Sortilin-related receptor (SORL1) | Q92673 |
| Scavenger receptor class B member 1 (SR-BI) | Q8WTV0 |
| CLSTN3 protein | Q8IUW6 |
| Neuroplastin | Q9Y639 |
| GRIK2 (glutamate receptor ionotropic, kainate 2) | Q8IY40 |
| NEDD8-activating enzyme E1 catalytic subunit | Q8TBC4 |
| ADP-ribosylation factor GTPase-activating protein 1 | Q8N6T3 |
| Voltage-dependent calcium channel subunit alpha-2/delta-3 | Q8IZS8 |
| Sodium/hydrogen exchanger 6 | Q92581 |
| Multimerin-1 | Q13201 |
| Hippocampus abundant transcript 1 protein | Q96MC6 |
| Lysyl oxidase homolog 4 | Q96JB6 |
| Hsp90 co-chaperone Cdc37 | Q16543 |
| Microtubule-associated serine/threonine-protein kinase 1 | Q9Y2H9 |
| VDAC3 (voltage-dependent anion-selective channel 3) | Q9Y277 |
| GTP:AMP phosphotransferase AK3, mitochondrial | Q9UIJ7 |
| Glutaryl-CoA dehydrogenase, mitochondrial | Q92947 |
| Programmed cell death protein 4 | Q53EL6 |

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## Cellular Components (`is active in` / `colocalizes with`)

APOE acts within and colocalizes with several cellular compartments including extracellular lipoprotein particles, the extracellular space, and endosomal/lysosomal pathways (via receptor-mediated endocytosis).

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## Summary

APOE (Apolipoprotein E) is one of the most functionally pleiotropic proteins in the human proteome, with connections spanning:

1. **Lipid & lipoprotein biology** — a core structural and functional component of all major lipoprotein classes, central to cholesterol transport, reverse cholesterol transport, and triglyceride homeostasis.
2. **Neuroscience** — binds amyloid-beta and tau; regulates dendritic spine development, synaptic plasticity, and long-term memory — explaining why the *APOE ε4* allele is the strongest genetic risk factor for late-onset Alzheimer disease.
3. **Cardiovascular biology** — modulates endothelial cell behavior, platelet activation, blood coagulation, and vascular development.
4. **Immunity** — suppresses inflammatory responses and regulates innate immunity.
5. **Virology** — participates in virion assembly and host-mediated activation of viral processes.

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*Created by [mcp-proto-okn](https://github.com/sbl-sdsc/mcp-proto-okn) 0.6.0 on 2026-03-16*

*Model: claude-sonnet-4-6*
