P18649

PR
Gene name
APOE
Protein name
Apolipoprotein E
Names
Apo-E
Species
Canis lupus familiaris (Dog) (Canis familiaris)
KEGG Pathway
cfa:476438
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-305 (Predicted disordered autoinhibitory region) PR

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P18649

Entry ID Method Resolution Chain Position Source
AF-P18649-F1 Predicted AlphaFoldDB

1 variants for P18649

Variant ID(s) Position Change Description Diseaes Association Provenance
rs21903676 93 K>E No EVA

No associated diseases with P18649

No regional properties for P18649

Type Name Position InterPro Accession
No domain, repeats, and functional sites for P18649

Functions

Description
EC Number
Subcellular Localization
  • Secreted
  • Secreted, extracellular space
  • Secreted, extracellular space, extracellular matrix
  • Extracellular vesicle
  • Endosome, multivesicular body
  • In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins
  • Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner
  • Lipidation induces the release from the extracellular matrix
  • Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

12 GO annotations of cellular component

Name Definition
chylomicron A large lipoprotein particle (diameter 75-1200 nm) composed of a central core of triglycerides and cholesterol surrounded by a protein-phospholipid coating. The proteins include one molecule of apolipoprotein B-48 and may include a variety of apolipoproteins, including APOAs, APOCs and APOE. Chylomicrons are found in blood or lymph and carry lipids from the intestines into other body tissues.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
extracellular matrix A structure lying external to one or more cells, which provides structural support, biochemical or biomechanical cues for cells or tissues.
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
high-density lipoprotein particle A lipoprotein particle with a high density (typically 1.063-1.21 g/ml) and a diameter of 5-10 nm that contains APOAs and may contain APOCs and APOE; found in blood and carries lipids from body tissues to the liver as part of the reverse cholesterol transport process.
intermediate-density lipoprotein particle A triglyceride-rich lipoprotein particle that typically contains APOB100, APOE and APOCs and has a density of 1.006-1.019 g/ml and a diameter of between 25-30 nm. IDL particles are found in blood and are formed by the delipidation of very-low-density lipoprotein particles (VLDL). IDL particles are removed from blood by the liver, following binding to the APOE receptor, or are converted to low-density lipoprotein (LDL).
low-density lipoprotein particle A lipoprotein particle, rich in cholesterol esters and low in triglycerides that is typically composed of APOB100 and APOE and has a density of 1.02-1.06 g/ml and a diameter of between 20-25 nm. LDL particles are formed from VLDL particles (via IDL) by the loss of triglyceride and gain of cholesterol ester. They transport endogenous cholesterol (and to some extent triglycerides) from peripheral tissues back to the liver.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
synaptic cleft The narrow gap that separates the presynaptic and postsynaptic membranes, into which neurotransmitter is released.
very-low-density lipoprotein particle A triglyceride-rich lipoprotein particle that is typically composed of APOB100, APOE and APOCs and has a density of about 1.006 g/ml and a diameter of between 20-80 nm. It is found in blood and transports endogenous products (newly synthesized cholesterol and triglycerides) from the liver.

15 GO annotations of molecular function

Name Definition
amyloid-beta binding Binding to an amyloid-beta peptide/protein.
antioxidant activity Inhibition of the reactions brought about by dioxygen (O2) or peroxides. Usually the antioxidant is effective because it can itself be more easily oxidized than the substance protected. The term is often applied to components that can trap free radicals, thereby breaking the chain reaction that normally leads to extensive biological damage.
cholesterol transfer activity Removes cholesterol from a membrane or a monolayer lipid particle, transports it through the aqueous phase while protected in a hydrophobic pocket, and brings it to an acceptor membrane or lipid particle.
enzyme binding Binding to an enzyme, a protein with catalytic activity.
heparan sulfate proteoglycan binding Binding to a heparan sulfate proteoglycan, any proteoglycan containing heparan sulfate as the glycosaminoglycan carbohydrate unit.
heparin binding Binding to heparin, a member of a group of glycosaminoglycans found mainly as an intracellular component of mast cells and which consist predominantly of alternating alpha-(1->4)-linked D-galactose and N-acetyl-D-glucosamine-6-sulfate residues.
identical protein binding Binding to an identical protein or proteins.
lipoprotein particle binding Binding to a lipoprotein particle. A lipoprotein particle, also known as a lipoprotein, is a clathrate complex consisting of a lipid enwrapped in a protein host without covalent binding in such a way that the complex has a hydrophilic outer surface consisting of all the protein and the polar ends of any phospholipids.
low-density lipoprotein particle receptor binding Binding to a low-density lipoprotein receptor.
metal chelating activity The formation of bonds from two or more atoms within the same ligand to a metal atom in complexes in which the metal is part of a ring.
phosphatidylcholine-sterol O-acyltransferase activator activity Increases the activity of phosphatidylcholine-sterol O-acyltransferase, an enzyme that converts cholesterol and phosphatidylcholine (lecithins) to cholesteryl esters and lyso-phosphatidylcholines.
phospholipid binding Binding to a phospholipid, a class of lipids containing phosphoric acid as a mono- or diester.
protein homodimerization activity Binding to an identical protein to form a homodimer.
tau protein binding Binding to tau protein. tau is a microtubule-associated protein, implicated in Alzheimer's disease, Down Syndrome and ALS.
very-low-density lipoprotein particle receptor binding Binding to a very-low-density lipoprotein receptor.

83 GO annotations of biological process

Name Definition
AMPA glutamate receptor clustering The glutamate receptor clustering process in which alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are localized to distinct domains in the cell membrane.
amyloid precursor protein metabolic process The chemical reactions and pathways involving amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease.
artery morphogenesis The process in which the anatomical structures of arterial blood vessels are generated and organized. Arteries are blood vessels that transport blood from the heart to the body and its organs.
cellular calcium ion homeostasis Any process involved in the maintenance of an internal steady state of calcium ions at the level of a cell.
cGMP-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via cyclic GMP (cGMP). Includes production of cGMP, and downstream effectors that further transmit the signal within the cell.
cholesterol catabolic process The chemical reactions and pathways resulting in the breakdown of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
cholesterol efflux The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
cholesterol homeostasis Any process involved in the maintenance of an internal steady state of cholesterol within an organism or cell.
chylomicron remnant clearance The process in which a chylomicron remnant is removed from the blood via receptor-mediated endocytosis into liver cells and its constituent parts degraded.
fatty acid homeostasis Any process involved in the maintenance of an internal steady state of fatty acid within an organism or cell.
G protein-coupled receptor signaling pathway The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
gene expression The process in which a gene's sequence is converted into a mature gene product (protein or RNA). This includes the production of an RNA transcript and its processing, translation and maturation for protein-coding genes.
high-density lipoprotein particle assembly The non-covalent aggregation and arrangement of proteins and lipids to form a high-density lipoprotein particle.
high-density lipoprotein particle clearance The process in which a high-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
high-density lipoprotein particle remodeling The acquisition, loss or modification of a protein or lipid within a high-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL.
intermediate-density lipoprotein particle clearance The process in which a intermediate-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
lipid transport involved in lipid storage The directed movement of lipids into cells that is part of their accumulation and maintenance.
lipoprotein biosynthetic process The chemical reactions and pathways resulting in the formation of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids.
lipoprotein catabolic process The chemical reactions and pathways resulting in the breakdown of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids.
locomotory exploration behavior The specific movement from place to place of an organism in response to a novel environment.
long-chain fatty acid transport The directed movement of long-chain fatty acids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
long-term memory The memory process that deals with the storage, retrieval and modification of information a long time (typically weeks, months or years) after receiving that information. This type of memory is typically dependent on gene transcription regulated by second messenger activation.
low-density lipoprotein particle remodeling The acquisition, loss or modification of a protein or lipid within a low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL.
maintenance of location in cell Any process in which a substance or cellular entity, such as a protein complex or organelle, is maintained in a specific location within, or in the membrane of, a cell, and is prevented from moving elsewhere.
negative regulation of amyloid fibril formation Any process that stops, prevents or reduces the frequency, rate or extent of amyloid fibril formation.
negative regulation of amyloid-beta formation Any process that stops, prevents or reduces the frequency, rate or extent of amyloid-beta formation.
negative regulation of blood vessel endothelial cell migration Any process that stops, prevents, or reduces the frequency, rate or extent of the migration of the endothelial cells of blood vessels.
negative regulation of canonical Wnt signaling pathway Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
negative regulation of cholesterol biosynthetic process Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of cholesterol.
negative regulation of endothelial cell proliferation Any process that stops, prevents, or reduces the rate or extent of endothelial cell proliferation.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of inflammatory response Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response.
negative regulation of long-term synaptic potentiation Any process that stops, prevents or reduces the frequency, rate or extent of long-term synaptic potentiation.
negative regulation of MAP kinase activity Any process that stops, prevents, or reduces the frequency, rate or extent of MAP kinase activity.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of neuron projection development Any process that decreases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
negative regulation of platelet activation Any process that decreases the rate or frequency of platelet activation. Platelet activation is a series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue.
negative regulation of protein secretion Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of a protein from a cell.
negative regulation of smooth muscle cell proliferation Any process that stops, prevents or reduces the rate or extent of smooth muscle cell proliferation.
negative regulation of triglyceride metabolic process Any process that decreases the frequency, rate or extent of the chemical reactions and pathways involving triglyceride, any triester of glycerol.
neuron projection development The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
nitric oxide mediated signal transduction Any intracellular signal transduction in which the signal is passed on within the cell via nitric oxide (NO). Includes synthesis of nitric oxide, receptors/sensors for nitric oxide (such as soluble guanylyl cyclase/sGC) and downstream effectors that further transmit the signal within the cell. Nitric oxide transmits its downstream effects through either cyclic GMP (cGMP)-dependent or independent mechanisms.
NMDA glutamate receptor clustering The receptor clustering process in which N-methyl-D-aspartate (NMDA) receptors are localized to distinct domains in the cell membrane.
phospholipid efflux The directed movement of a phospholipid out of a cell or organelle.
positive regulation by host of viral process A process in which a host organism activates or increases the frequency, rate or extent of the release of a process being mediated by a virus with which it is infected.
positive regulation of amyloid-beta clearance Any process that activates or increases the frequency, rate or extent of amyloid-beta clearance.
positive regulation of cholesterol efflux Any process that increases the frequency, rate or extent of cholesterol efflux. Cholesterol efflux is the directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
positive regulation of cholesterol metabolic process Any process that increases the rate, frequency, or extent of cholesterol metabolism, the chemical reactions and pathways involving cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
positive regulation of CoA-transferase activity Any process that activates or increases the frequency, rate or extent of CoA-transferase activity.
positive regulation of dendritic spine development Any process that increases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
positive regulation of dendritic spine maintenance Any process that activates or increases the frequency, rate or extent of dendritic spine maintenance.
positive regulation of DNA-templated transcription Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of endocytosis Any process that activates or increases the frequency, rate or extent of endocytosis.
positive regulation of ERK1 and ERK2 cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of heparan sulfate binding Any process that activates or increases the frequency, rate or extent of heparan sulfate binding.
positive regulation of heparan sulfate proteoglycan binding Any process that activates or increases the frequency, rate or extent of heparan sulfate proteoglycan binding.
positive regulation of lipid biosynthetic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
positive regulation of lipid transport across blood-brain barrier Any process that activates or increases the frequency, rate or extent of lipid transport across blood-brain barrier.
positive regulation of low-density lipoprotein particle receptor catabolic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of low-density lipoprotein particle receptors.
positive regulation of membrane protein ectodomain proteolysis Any process that activates or increases the frequency, rate or extent of membrane protein ectodomain peptidolysis.
positive regulation of neuron projection development Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of nitric-oxide synthase activity Any process that activates or increases the activity of the enzyme nitric-oxide synthase.
positive regulation of phospholipid efflux Any process that activates or increases the frequency, rate or extent of phospholipid efflux.
protein import The targeting and directed movement of proteins into a cell or organelle. Not all import involves an initial targeting event.
receptor-mediated endocytosis An endocytosis process in which cell surface receptors ensure specificity of transport. A specific receptor on the cell surface binds tightly to the extracellular macromolecule (the ligand) that it recognizes; the plasma-membrane region containing the receptor-ligand complex then undergoes endocytosis, forming a transport vesicle containing the receptor-ligand complex and excluding most other plasma-membrane proteins. Receptor-mediated endocytosis generally occurs via clathrin-coated pits and vesicles.
regulation of amyloid-beta clearance Any process that modulates the frequency, rate or extent of amyloid-beta clearance.
regulation of behavioral fear response Any process that modulates the frequency, rate or extent of behavioral fear response.
regulation of Cdc42 protein signal transduction Any process that modulates the frequency, rate or extent of Cdc42 protein signal transduction.
regulation of cellular response to very-low-density lipoprotein particle stimulus Any process that modulates the frequency, rate or extent of cellular response to very-low-density lipoprotein particle stimulus.
regulation of innate immune response Any process that modulates the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection.
regulation of proteasomal protein catabolic process Any process that modulates the rate, frequency, or extent of the chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds that is mediated by the proteasome.
regulation of protein-containing complex assembly Any process that modulates the frequency, rate or extent of protein complex assembly.
response to caloric restriction A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caloric restriction, insufficient food energy intake.
response to dietary excess The physiological process in which dietary excess is sensed by the central nervous system, resulting in a reduction in food intake and increased energy expenditure.
response to oxidative stress Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
reverse cholesterol transport The directed movement of peripheral cell cholesterol, cholest-5-en-3-beta-ol, towards the liver for catabolism.
triglyceride homeostasis Any process involved in the maintenance of an internal steady state of triglyceride within an organism or cell.
triglyceride metabolic process The chemical reactions and pathways involving triglyceride, any triester of glycerol. The three fatty acid residues may all be the same or differ in any permutation. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
triglyceride-rich lipoprotein particle clearance The process in which a triglyceride-rich lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
vasodilation An increase in the internal diameter of blood vessels, especially arterioles or capillaries, due to relaxation of smooth muscle cells that line the vessels, and usually resulting in a decrease in blood pressure.
very-low-density lipoprotein particle clearance The process in which a very-low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
very-low-density lipoprotein particle remodeling The acquisition, loss or modification of a protein or lipid within a very-low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase or lipoprotein lipase and the subsequent loss of free fatty acid.
virion assembly A late phase of the viral life cycle during which all the components necessary for the formation of a mature virion collect at a particular site in the cell and the basic structure of the virus particle is formed.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q03247 APOE Apolipoprotein E Bos taurus (Bovine) PR
P02649 APOE Apolipoprotein E Homo sapiens (Human) PR
P08226 Apoe Apolipoprotein E Mus musculus (Mouse) PR
P02650 Apoe Apolipoprotein E Rattus norvegicus (Rat) PR
10 20 30 40 50 60
MKVLWAALVV TLLAGCWADV QPEPELEREL EPKVQQELEP EAGWQTGQPW EAALARFWDY
70 80 90 100 110 120
LRWVQTLSDQ VQEGVLNTQV TQELTALMDE TMKEVKAYKA ELDEQLGPMT SETQARVAKE
130 140 150 160 170 180
LQAAQARLRS DMEDVRNRLT QYRGELQAML GQSSEELRAR FASHMRKLRK RVLRDAEDLQ
190 200 210 220 230 240
RRLAVYKAGV REGAERSVSS IRERLWPLLE QARERNAKVG ALATQPLLER ADALGQQLRG
250 260 270 280 290 300
QLEEMSSRAR GHLEEMREQI QEVRVKMEEQ ADQIRQKAEA FQARLKSWFE PLLEDMQRQW
310 320
DGLVEKVQAA VATIPTSKPV EEP