APOE_AOTNA
ID APOE_AOTNA Reviewed; 281 AA.
AC P0DKW5; A0A2K5DKL6;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2019, sequence version 2.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Aotus nancymaae (Ma's night monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Aotidae;
OC Aotus.
OX NCBI_TaxID=37293;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Hughes D.S., Murali S., Raveendran M., Korchina V., Bandaranaike D.,
RA Bellair M., Blankenburg K., Chao H., Dahdouli M., Dinh H., Doddapaneni H.,
RA Jayaseelan J., Khan Z., Kovar C., Kurapati P., Le B., Lee S.,
RA Lorensuhewa L., Mathew T., Narasimhan A., Okwuonu G., Osuji N., Otenyo P.,
RA Qu C., Quiroz J., Raj R., Rajbhandari K., Santibanez J., Skinner E.,
RA Wang Y., Xin Y., Han Y., Muzny D.M., Richards S., Worley K.C., Rogers J.,
RA Gibbs R.A.;
RT "Owl monkey reference genome and diversity panel.";
RL Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (NOV-2012).
CC -!- FUNCTION: APOE is an apolipoprotein, a protein associating with lipid
CC particles, that mainly functions in lipoprotein-mediated lipid
CC transport between organs via the plasma and interstitial fluids. APOE
CC is a core component of plasma lipoproteins and is involved in their
CC production, conversion and clearance. Apoliproteins are amphipathic
CC molecules that interact both with lipids of the lipoprotein particle
CC core and the aqueous environment of the plasma. As such, APOE
CC associates with chylomicrons, chylomicron remnants, very low density
CC lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but
CC shows a preferential binding to high-density lipoproteins (HDL). It
CC also binds a wide range of cellular receptors including the LDL
CC receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8
CC and the very low-density lipoprotein receptor/VLDLR that mediate the
CC cellular uptake of the APOE-containing lipoprotein particles. Finally,
CC APOE has also a heparin-binding activity and binds heparan-sulfate
CC proteoglycans on the surface of cells, a property that supports the
CC capture and the receptor-mediated uptake of APOE-containing
CC lipoproteins by cells. A main function of APOE is to mediate
CC lipoprotein clearance through the uptake of chylomicrons, VLDLs, and
CC HDLs by hepatocytes. APOE is also involved in the biosynthesis by the
CC liver of VLDLs as well as their uptake by peripheral tissues ensuring
CC the delivery of triglycerides and energy storage in muscle, heart and
CC adipose tissues. By participating in the lipoprotein-mediated
CC distribution of lipids among tissues, APOE plays a critical role in
CC plasma and tissues lipid homeostasis. APOE is also involved in two
CC steps of reverse cholesterol transport, the HDLs-mediated transport of
CC cholesterol from peripheral tissues to the liver, and thereby plays an
CC important role in cholesterol homeostasis. First, it is functionally
CC associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it
CC is enriched in circulating HDLs and mediates their uptake by
CC hepatocytes. APOE also plays an important role in lipid transport in
CC the central nervous system, regulating neuron survival and sprouting.
CC {ECO:0000250|UniProtKB:P02649}.
CC -!- SUBUNIT: Homotetramer. May interact with ABCA1; functionally associated
CC with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-
CC beta peptide; the interaction is extremely stable in vitro but its
CC physiological significance is unclear. May interact with MAPT. May
CC interact with MAP2. In the cerebrospinal fluid, interacts with secreted
CC SORL1. {ECO:0000250|UniProtKB:P02649}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}.
CC Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. Secreted,
CC extracellular space, extracellular matrix
CC {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is associated
CC with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL
CC lipoproteins. Lipid poor oligomeric APOE is associated with the
CC extracellular matrix in a calcium- and heparan-sulfate proteoglycans-
CC dependent manner. Lipidation induces the release from the extracellular
CC matrix. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: APOE exists as multiple glycosylated and sialylated glycoforms
CC within cells and in plasma. The extent of glycosylation and sialylation
CC are tissue and context specific. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: Glycated in plasma VLDL. {ECO:0000250|UniProtKB:P02649}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P02649}.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC {ECO:0000305}.
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DR EMBL; AC146520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DKW5; -.
DR SMR; P0DKW5; -.
DR STRING; 37293.ENSANAP00000021488; -.
DR Ensembl; ENSANAT00000039376; ENSANAP00000021488; ENSANAG00000028543.
DR GeneTree; ENSGT00950000182929; -.
DR OMA; WFEPLVQ; -.
DR Proteomes; UP000233020; Unplaced.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0034364; C:high-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0034363; C:intermediate-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0034362; C:low-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0043083; C:synaptic cleft; IEA:Ensembl.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0016209; F:antioxidant activity; IEA:Ensembl.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0071813; F:lipoprotein particle binding; IEA:Ensembl.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:UniProtKB.
DR GO; GO:0046911; F:metal chelating activity; IEA:Ensembl.
DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IEA:Ensembl.
DR GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0048156; F:tau protein binding; IEA:Ensembl.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; IEA:Ensembl.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; IEA:Ensembl.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0034382; P:chylomicron remnant clearance; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; ISS:UniProtKB.
DR GO; GO:0034384; P:high-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0071831; P:intermediate-density lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0010877; P:lipid transport involved in lipid storage; IEA:Ensembl.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0015909; P:long-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IEA:Ensembl.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0010544; P:negative regulation of platelet activation; IEA:Ensembl.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IEA:Ensembl.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0033700; P:phospholipid efflux; IEA:Ensembl.
DR GO; GO:0044794; P:positive regulation by host of viral process; IEA:Ensembl.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IEA:Ensembl.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:1905920; P:positive regulation of CoA-transferase activity; IEA:Ensembl.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IEA:Ensembl.
DR GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:1905855; P:positive regulation of heparan sulfate binding; IEA:Ensembl.
DR GO; GO:1905860; P:positive regulation of heparan sulfate proteoglycan binding; IEA:Ensembl.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IEA:Ensembl.
DR GO; GO:1903002; P:positive regulation of lipid transport across blood-brain barrier; IEA:Ensembl.
DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; IEA:Ensembl.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:1902995; P:positive regulation of phospholipid efflux; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0017038; P:protein import; IEA:Ensembl.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:2000822; P:regulation of behavioral fear response; IEA:Ensembl.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IEA:Ensembl.
DR GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:0045088; P:regulation of innate immune response; IEA:Ensembl.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0061771; P:response to caloric restriction; IEA:Ensembl.
DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0043691; P:reverse cholesterol transport; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0019068; P:virion assembly; IEA:Ensembl.
DR InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 2.
PE 3: Inferred from homology;
KW Chylomicron; Extracellular matrix; HDL; Heparin-binding; Lipid transport;
KW Lipid-binding; Oxidation; Phosphoprotein; Reference proteome; Repeat;
KW Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..281
FT /note="Apolipoprotein E"
FT /id="PRO_0000420992"
FT REPEAT 82..103
FT /note="1"
FT REPEAT 104..125
FT /note="2"
FT REPEAT 126..147
FT /note="3"
FT REPEAT 148..169
FT /note="4"
FT REPEAT 198..219
FT /note="5"
FT REGION 82..219
FT /note="5 X 22 AA approximate tandem repeats"
FT REGION 160..170
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 230..281
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 242..254
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 164..167
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 193..200
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 145
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 281 AA; 32367 MW; E51FCA3CBEAFC7A5 CRC64;
MKVLWAALLI ALLAGCQGKM EQVVEPELEP EPELHQQADW QSGQPWELAL GRFWDYLRWV
QTLSEQVQEE LLSSQVTQEL TALMDETMKE LKAYKSELEE QLSPVAEETR ARLSKELQAA
QARLGADMED VRSRLAQYRS EVQAMLGQST DELRARLTSH LRKLRTVSYT HLDVYKRQSL
ASQPLQERAQ AWGERLRTRM EEVGSRTRDR LDEVKEQVEE VRAKLEEQAQ QMRLQAEAFQ
ARLKSWFEPL VEDMQRQWAG LVEKVQAAVG ASAAPVPSDN H
