APOE_DICBI
ID APOE_DICBI Reviewed; 316 AA.
AC P0DUI9;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 1.
DT 03-AUG-2022, entry version 6.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Diceros bicornis (Black rhinoceros).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Rhinocerotidae; Diceros.
OX NCBI_TaxID=9805;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Johnson J., Muren E., Swofford R., Turner-Maier J., Marinescu V.D.,
RA Genereux D.P., Alfoldi J., Birren B., Karlsson E.K., Lindblad-Toh K.;
RL Submitted (MAR-2019) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (JAN-2021).
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 -!- 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; PVJY020000258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DUI9; -.
DR SMR; P0DUI9; -.
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 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; Repeat;
KW Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..316
FT /note="Apolipoprotein E"
FT /id="PRO_0000452454"
FT REPEAT 83..104
FT /note="1"
FT REPEAT 105..126
FT /note="2"
FT REPEAT 127..148
FT /note="3"
FT REPEAT 149..170
FT /note="4"
FT REPEAT 171..192
FT /note="5"
FT REPEAT 193..214
FT /note="6"
FT REPEAT 215..232
FT /note="7"
FT REPEAT 233..254
FT /note="8"
FT REGION 83..254
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 161..171
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 213..289
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 265..316
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 277..289
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 165..168
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 228..235
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 316 AA; 35672 MW; 01AEB1DBDCE91E65 CRC64;
MKVLWAALVV TLLAGCGADV EPGPEVQPGP EVQLGKEWAT WQASQPWEQA LGRFWNYLRW
VQTLSEKVQE QLLSSQVTEE LTALMDDTMK EVKACKSELE EQLGPVTEET KARVSKELQA
AQARLGADME EVRSRLAQYR GELQAMVGQS TEELRGRLSA HLRKLRKRLL RDAEDLQRRL
AVYQAGIREG AARSVNTLRE HLGPLAEQAA TVHTLVSKPL QERAEAWAQR LRGRLEKAGF
PVGDRLDEVR EQVQEVRAKV EEQANQVRLQ AEAFQGRLKS WFEPLVQDMQ QKWAELVEKV
QLAVGAVPTS VPSEKQ
