APOE_CHLSB
ID APOE_CHLSB Reviewed; 323 AA.
AC A0A0D9S1R0;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=60711;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Warren W., Wilson R.K.;
RL Submitted (MAR-2014) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (APR-2019).
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; AQIB01135960; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A0D9S1R0; -.
DR SMR; A0A0D9S1R0; -.
DR STRING; 60711.ENSCSAP00000014799; -.
DR eggNOG; ENOG502QVD6; Eukaryota.
DR OrthoDB; 1314660at2759; -.
DR BioGRID-ORCS; 103234841; 1 hit in 13 CRISPR screens.
DR Proteomes; UP000029965; Unplaced.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
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:0034361; C:very-low-density lipoprotein particle; ISS:UniProtKB.
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:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:UniProtKB.
DR GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0034382; P:chylomicron remnant clearance; ISS:UniProtKB.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; ISS:UniProtKB.
DR GO; GO:0071831; P:intermediate-density lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; ISS:UniProtKB.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:UniProtKB.
DR GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; ISS:UniProtKB.
DR InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 1.
PE 3: Inferred from homology;
KW Chylomicron; Extracellular matrix; Glycoprotein; HDL; Heparin-binding;
KW Lipid transport; Lipid-binding; Oxidation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..323
FT /note="Apolipoprotein E"
FT /id="PRO_5002346112"
FT REPEAT 86..107
FT /note="1"
FT REPEAT 108..129
FT /note="2"
FT REPEAT 130..151
FT /note="3"
FT REPEAT 152..173
FT /note="4"
FT REPEAT 174..195
FT /note="5"
FT REPEAT 196..217
FT /note="6"
FT REPEAT 218..239
FT /note="7"
FT REPEAT 240..261
FT /note="8"
FT REGION 86..261
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 164..174
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 216..296
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 272..323
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 284..296
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 168..171
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 235..242
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 149
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT CARBOHYD 218
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 323 AA; 36558 MW; 7B0897F43B883D6A CRC64;
MKVLWAALLV TFLAGCQAAA DAPIKVEQPV EPETEPELRP QTEWQSGQPW ELALGRFWDY
LRWVQTLSEQ VQEELLSPQV TQELTTLMDE TMKELKAYKS ELEEQLSPVA EETRARLSKE
LQAAQARLGA DMEDVRSRLV QYRSEVQAML GQSTEELRAR LASHLRKLRK RLLRDADDLQ
KRLAVYQAGA REGAERGVSA IRERLGPLVE QGRVRAATVG SLASQPLQER AQALGERLRA
RMEEMGSRTR DRLDEVKEQV AEVRAKLEEQ AQQISLQAEA FQARLKSWFE PLVEDMQRQW
AGLVEKVQAA VGASTAPVPS DNH
