Tbio APOE Apolipoprotein E

Protein Summary

Description

APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating to the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:9395455, PubMed:14754908, PubMed:23620513). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:8939961, PubMed:25173806). APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). APOE, may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074). The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]

Uniprot Accession IDs

• P02649
• B2RC15
• C0JYY5
• Q9P2S4
• Apo-E

Gene Name

• APOE

Ensembl ID

• ENST00000252486
• ENSP00000252486
• ENSG00000130203

Symbol

• AD2
• LPG
• APO-E
• ApoE4
• LDLCQ5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
metabolite	1
molecular function	1
chemical	0.95
disease	0.94

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 21858.14   (req: < 5)

Gene RIFs: 2432   (req: <= 3)

Antibodies: 1289   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 21858.14   (req: >= 5)

Gene RIFs: 2432   (req: > 3)

Antibodies: 1289   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 131

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (74)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 74

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Alzheimer's disease	EFO_0000249	14	6	3	3.1	99.9
low density lipoprotein cholesterol measurement	EFO_0004611	13	4	20	12	99.8
longevity	EFO_0004300	5	3	1	1.6	99.5
C-reactive protein measurement	EFO_0004458	5	2	6		99.3
high density lipoprotein cholesterol measurement	EFO_0004612	9	3	14	12	99.2

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Alzheimer's disease	EFO_0000249	3	3.1	99.9
low density lipoprotein cholesterol measurement	EFO_0004611	20	12	99.8
longevity	EFO_0004300	1	1.6	99.5
C-reactive protein measurement	EFO_0004458	6		99.3
high density lipoprotein cholesterol measurement	EFO_0004612	14	12	99.2

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Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	apolipoprotein E		449586
Macaque	apolipoprotein E		714623
Mouse	apolipoprotein E	MGI:88057	11816
Rat	apolipoprotein E	RGD:2138	25728
Dog	apolipoprotein E	VGNC:38002	476438

Species	Name	OMA	EggNOG	Inparanoid
Chimp	apolipoprotein E
Macaque	apolipoprotein E
Mouse	apolipoprotein E
Rat	apolipoprotein E
Dog	apolipoprotein E

Protein Structure (17 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P02649-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 17

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (42)

Reactome (32)

KEGG (2)

WikiPathways (8)

Binding and Uptake of Ligands by Scavenger Receptors (R-HSA-2173782)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Binding and Uptake of Ligands by Scavenger Receptors	116 targets	R-HSA-2173782
Reactome	Chylomicron assembly	10 targets	R-HSA-8963888
Reactome	Chylomicron clearance	5 targets	R-HSA-8964026
Reactome	Chylomicron remodeling	10 targets	R-HSA-8963901
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594

Name	Explore in Pharos	Explore in Source
Binding and Uptake of Ligands by Scavenger Receptors	116 targets	R-HSA-2173782
Chylomicron assembly	10 targets	R-HSA-8963888
Chylomicron clearance	5 targets	R-HSA-8964026
Chylomicron remodeling	10 targets	R-HSA-8963901
G alpha (i) signalling events	408 targets	R-HSA-418594

Gene Ontology Terms (158)

Functions (19)

Components (27)

Processes (112)

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1 – 10 of 19

GO Term	Evidence	Assigned by
amyloid-beta binding	Inferred from Direct Assay (IDA)	UniProtKB
antioxidant activity	Inferred from Direct Assay (IDA)	BHF-UCL
heparin binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
lipid binding	Inferred from Direct Assay (IDA)	UniProtKB
lipid transporter activity	Inferred from Direct Assay (IDA)	BHF-UCL
low-density lipoprotein particle receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
metal chelating activity	Inferred from Direct Assay (IDA)	BHF-UCL
phosphatidylcholine-sterol O-acyltransferase activator activity	Inferred from Direct Assay (IDA)	BHF-UCL
phospholipid binding	Inferred from Direct Assay (IDA)	BHF-UCL

Protein-Protein Interactions (482)

Explore Interacting Targets

1 – 10 of 482

• See Interactions on String-DB

MANSC1

Tdark

Novelty: 0.91681036

p_int: 0.999998892

p_ni: 0.000001108

Data Source: BioPlex

HLA-DPA1

Tbio

Novelty: 0.01080446

p_int: 0.999998035

p_ni: 0.000001965

Data Source: BioPlex

MMRN1

Tbio

Novelty: 0.03378128

p_int: 0.999960004

p_ni: 0.000039913

p_wrong: 8.2e-8

Score: 0.2

Data Source: BioPlex,STRINGDB

VDAC1

Tbio

Novelty: 0.0011441

p_int: 0.999949506

p_ni: 0.000050386

p_wrong: 1.08e-7

Score: 0.694

Data Source: BioPlex,STRINGDB

MMP3

Tchem

Novelty: 0.00041675

p_int: 0.999922274

p_ni: 0.000077208

p_wrong: 5.18e-7

Score: 0.821

Data Source: BioPlex,STRINGDB

C16orf92

Tdark

Novelty: 3.33740474

p_int: 0.999920991

p_ni: 0.000079008

p_wrong: 1e-9

Data Source: BioPlex

C9

Tbio

Novelty: 0.00749298

p_int: 0.999854944

p_ni: 0.000144993

p_wrong: 6.3e-8

Score: 0.401

Data Source: BioPlex,STRINGDB

APOC2

Tbio

Novelty: 0.0015496

p_int: 0.999179357

p_ni: 0.000811847

p_wrong: 0.000008796

Score: 0.993

Data Source: BioPlex,Reactome,STRINGDB

VDAC3

Tbio

Novelty: 0.0095068

p_int: 0.999125127

p_ni: 0.000874846

p_wrong: 2.7e-8

Score: 0.225

Data Source: BioPlex,STRINGDB

MMP10

Tchem

Novelty: 0.00112113

p_int: 0.997865595

p_ni: 0.002132562

p_wrong: 0.000001842

Score: 0.694

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  21858.14

PubMed score by year

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PubTator Score  11855.59

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alzheimer disease
Amyloidosis
Cholesterol metabolism
Chylomicron
Complete proteome
Direct protein sequencing
Disease mutation
Extracellular matrix
Glycation

GWAS Trait Find Similar Targets

acute coronary syndrome
age-related macular degeneration
Agents acting on the renin-angiotensin system use measurement
alcohol abuse
Alzheimer's disease
Antithrombotic agent use measurement
apolipoprotein A 1 measurement
aspirin use measurement
atrophic macular degeneration
beta-amyloid 1-42 measurement

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype