APOE_CAVPO
ID APOE_CAVPO Reviewed; 298 AA.
AC P23529;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2308832; DOI=10.1093/nar/18.1.202;
RA Matsushima T., Getz G.S., Meredith S.C.;
RT "Primary structure of guinea pig apolipoprotein E.";
RL Nucleic Acids Res. 18:202-202(1990).
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 and the very low-density lipoprotein receptor/VLDLR that
CC mediate the cellular uptake of the APOE-containing lipoprotein
CC particles. Finally, APOE has also a heparin-binding activity and binds
CC heparan-sulfate proteoglycans on the surface of cells, a property that
CC supports the capture and the receptor-mediated uptake of APOE-
CC containing lipoproteins by cells. {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 PIR; S12635; S12635.
DR AlphaFoldDB; P23529; -.
DR SMR; P23529; -.
DR eggNOG; ENOG502QVD6; Eukaryota.
DR InParanoid; P23529; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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: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..298
FT /note="Apolipoprotein E"
FT /id="PRO_0000001985"
FT REPEAT 74..95
FT /note="1"
FT REPEAT 96..117
FT /note="2"
FT REPEAT 118..139
FT /note="3"
FT REPEAT 140..161
FT /note="4"
FT REPEAT 162..183
FT /note="5"
FT REPEAT 184..204
FT /note="6"
FT REPEAT 205..222
FT /note="7"
FT REPEAT 223..244
FT /note="8"
FT REGION 74..244
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 152..162
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 260..272
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 156..159
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 218..225
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 137
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 298 AA; 34211 MW; 2B74C1A7F59FD70B CRC64;
MKVLWAALVV TLLAGCRADV EPEVEVREPA VWQSGQPWEL ALSRFWDYLR WVQTLSDQVQ
EELLSNQVTQ ELTLLIEDTM KEVKAYKAEL EKELGPVAED TKARLAKELQ AAQARLGADM
EEVRNRLSQY RSEVQAMLGQ SSEELRARLT SHPRKMKRRL QRDIDELQKR MAVYKAGAQE
GAERGVSAIR ERLGSLIEQG RLQALASQPL QERAQAWGEQ MRGRLEKVGS QARDRLEEVR
EQMEEVRVKV EEQAEAFQAR LKSWFEPMME DMRRQWAELI QKVQVAVGAS TSAPSQEP
