APOE_ACIJB
ID APOE_ACIJB Reviewed; 304 AA.
AC P0DSE0;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Acinonyx jubatus (Cheetah).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Acinonychinae;
OC Acinonyx.
OX NCBI_TaxID=32536;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Scott A., Pukazhenthi B., Koepfli K.-P., Mohr D., Crosier A., O'Brien S.J.,
RA Tamazian G., Dobrynin P., Komissarov A., Kliver S., Krasheninnikova K.;
RL Submitted (AUG-2018) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (FEB-2019).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 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 EMBL; QURD01003266; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DSE0; -.
DR SMR; P0DSE0; -.
DR Proteomes; UP000504626; Unplaced.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0034364; C:high-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0042157; P:lipoprotein metabolic process; IEA:InterPro.
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 InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 1.
PE 3: Inferred from homology;
KW Chylomicron; Extracellular matrix; HDL; Heparin-binding; Lipid transport;
KW Lipid-binding; Phosphoprotein; Reference proteome; Repeat; Secreted;
KW Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..304
FT /note="Apolipoprotein E"
FT /id="PRO_0000446922"
FT REPEAT 78..99
FT /note="1"
FT REPEAT 100..121
FT /note="2"
FT REPEAT 122..143
FT /note="3"
FT REPEAT 144..165
FT /note="4"
FT REPEAT 166..187
FT /note="5"
FT REPEAT 188..208
FT /note="6"
FT REPEAT 209..220
FT /note="7"
FT REPEAT 221..242
FT /note="8"
FT REGION 78..242
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 156..166
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 208..277
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 253..304
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 265..277
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 160..163
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 216..223
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 304 AA; 34977 MW; BE6C4B455F52F463 CRC64;
MKVLWAALLV ALLAGCWADV EPEPQLEREL EPEAPWQASQ PWEQALGRFR DYLRWVQTLS
DQVQEEVLNT QVTQELTVLM EETMKEVKAY REELEEQLGP MASETQARVA KELQAAQARL
GSDMEDVRNR LAQYRSEVQA MLGQSAEELR ARLASHLRKL RKRLLRDAED LHKRLAVYRA
GVREGAERSV SSIRERFWPL VEQARARNAN VAAVAAQPLR ERAEALGQQL RGRLDEVREQ
VEEMRVKMEE QADQMRQQAE AFQARLKSWF EPLVQDMQRQ WAGLVEKLQA AVGTSPTTAP
VEKQ
