APOE_CAPHE
ID APOE_CAPHE Reviewed; 316 AA.
AC P0DN38;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Capra hircus aegagrus (Wild goat) (Capra aegagrus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Capra.
OX NCBI_TaxID=9923;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Streeter I.;
RL Submitted (FEB-2014) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (OCT-2015).
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; CBYH010014123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DN38; -.
DR SMR; P0DN38; -.
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; 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_0000435010"
FT REPEAT 79..100
FT /note="1"
FT REPEAT 101..122
FT /note="2"
FT REPEAT 123..144
FT /note="3"
FT REPEAT 145..166
FT /note="4"
FT REPEAT 167..188
FT /note="5"
FT REPEAT 189..210
FT /note="6"
FT REPEAT 211..232
FT /note="7"
FT REPEAT 233..254
FT /note="8"
FT REGION 79..254
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 157..167
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 209..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 161..164
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"
FT MOD_RES 142
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT CARBOHYD 211
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 316 AA; 36083 MW; EDB7482D80BF2A61 CRC64;
MKVLWVALVV ALLAGCQADM EGELGSEEPL PPEQPRGQDS QPWEQVLGRL WDYLRWVQTL
SDQVQEELLN TQVIQELTVL MEETMKEVKA YREELEGQLA PMAQETQARV SKELQAAQAR
LGSDMEDLRN RLAQYRSEVQ AMLGQSTEEL RARMASHLRK LRKRLLRDAD DLKKRLAVYQ
AGASEGAERS VSAIRERLRP LVEQGQSRAA TLSTQAAQPL LDRAEAWRQK LHGRLEEVGV
RAQDRLDKMR QQLEEVRAKV EEQGSQIRLQ AEAFQARLRS WFEPLVGDMQ RQWAGLVEKV
QLALHLSPTS PPSENH
