APOE_PTEPE
ID APOE_PTEPE Reviewed; 308 AA.
AC P0DUJ2;
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 Pteropus pselaphon (Bonin flying fox).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Chiroptera; Megachiroptera; Pteropodidae;
OC Pteropodinae; Pteropus.
OX NCBI_TaxID=1496133;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Nakajima N., Onuma M., Endoh D., Nagamine T., Nakaya Y.;
RT "Draft genome sequence of Bonin flying fox.";
RL Submitted (AUG-2020) 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RL Unpublished observations (JAN-2021).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; BMBI01005855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DUJ2; -.
DR SMR; P0DUJ2; -.
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..308
FT /note="Apolipoprotein E"
FT /id="PRO_0000452457"
FT REPEAT 75..96
FT /note="1"
FT REPEAT 97..118
FT /note="2"
FT REPEAT 119..140
FT /note="3"
FT REPEAT 141..162
FT /note="4"
FT REPEAT 163..184
FT /note="5"
FT REPEAT 185..206
FT /note="6"
FT REPEAT 207..224
FT /note="7"
FT REPEAT 225..246
FT /note="8"
FT REGION 75..246
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 153..163
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 205..281
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 257..308
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 269..281
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 157..160
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 220..227
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 308 AA; 35409 MW; D6D93E2392DFFCF0 CRC64;
MKFLWAALVV TLLAGCRADV EEEVKLGQEP DRWQAKQPWE QALGRFWEYL RWVQTLSNKV
KEELLNSQVT EELKLLIEET MKEVKAYKEE LEKQVGPIAQ ETQARLSKEL QAAQARLESD
MEDVRTRLAQ YRSEAQAALG QNTDDLQGRL ASHLRKLRKR LLRDAEDLQK RLAVYQAGTH
EAAERGVSAI HERLGPLMME GPLQAIPPSQ QLRERAEAWG QKVRGRLESV GSQARDRLDD
MRDQMEELKA KVEEQASQVR LQAEAFQTRL KSWFEPLVQD MQRQWASLVE KVQSTLGISP
STKPSKTK
