APOE_CERSS
ID APOE_CERSS Reviewed; 310 AA.
AC P0DUI6;
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 Ceratotherium simum simum (Southern white rhinoceros).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Rhinocerotidae; Ceratotherium.
OX NCBI_TaxID=73337;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Di Palma F., Alfoldi J., Johnson J., Berlin A., Gnerre S., Jaffe D.,
RA MacCallum I., Young S., Walker B.J., Lindblad-Toh K.;
RT "The Draft Genome of Ceratotherium simum.";
RL Submitted (MAY-2012) 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RL Unpublished observations (JAN-2021).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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AKZM01045079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_014650742.1; XM_014795256.1.
DR AlphaFoldDB; P0DUI6; -.
DR SMR; P0DUI6; -.
DR GeneID; 101406349; -.
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..310
FT /note="Apolipoprotein E"
FT /id="PRO_0000452451"
FT REPEAT 77..98
FT /note="1"
FT REPEAT 99..120
FT /note="2"
FT REPEAT 121..142
FT /note="3"
FT REPEAT 143..164
FT /note="4"
FT REPEAT 165..186
FT /note="5"
FT REPEAT 187..208
FT /note="6"
FT REPEAT 209..226
FT /note="7"
FT REPEAT 227..248
FT /note="8"
FT REGION 77..248
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 155..165
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 207..283
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 259..310
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 271..283
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 159..162
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 222..229
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 310 AA; 35170 MW; B7661E2D1521688B CRC64;
MKVLWAALVV TLLAGCGADV EPGPEVQLGK EWATWQASQP WEQALGRFWN YLRWVQTLSE
QVQEQLLSSQ VTEELTALMD DTMKEVKACQ SELEEQLGPV TEETKARVSK ELQAAQARLG
ADMEEVRSRL AQYRGELQAM VGQSTEELRG RLSAHLRKMR KRLLRDAEDL QRRLAVYQAG
IWEGAERSVN TLREHLGPLA EQAATVHTLV SKPLQERAEA WAQRLRGRLE KAGFPVGDRL
DEVREQVQEV RAKVEEQANQ VRLQAEAFQG RLKSWFEPLV QDMQQKWAEL VEKVQLAVGA
VPTSVPSEKQ
