APOE_ATEGE
ID APOE_ATEGE Reviewed; 322 AA.
AC P0DKW6;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Ateles geoffroyi (Black-handed spider monkey) (Geoffroy's spider monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Atelidae;
OC Atelinae; Ateles.
OX NCBI_TaxID=9509;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Cheng J.-F., Hamilton M., Peng Y., Hosseini R., Peng Z., Malinov I.,
RA Rubin E.M.;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (NOV-2012).
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, the LDL receptor-related proteins LRP1, LRP2 and LRP8
CC and the very low-density lipoprotein receptor/VLDLR that mediate the
CC cellular uptake of the APOE-containing lipoprotein particles. Finally,
CC APOE has also a heparin-binding activity and binds heparan-sulfate
CC proteoglycans on the surface of cells, a property that supports the
CC capture and the receptor-mediated uptake of APOE-containing
CC lipoproteins by cells. A main function of APOE is to mediate
CC lipoprotein clearance through the uptake of chylomicrons, VLDLs, and
CC HDLs by hepatocytes. APOE is also involved in the biosynthesis by the
CC liver of VLDLs as well as their uptake by peripheral tissues ensuring
CC the delivery of triglycerides and energy storage in muscle, heart and
CC adipose tissues. By participating in the lipoprotein-mediated
CC distribution of lipids among tissues, APOE plays a critical role in
CC plasma and tissues lipid homeostasis. APOE is also involved in two
CC steps of reverse cholesterol transport, the HDLs-mediated transport of
CC cholesterol from peripheral tissues to the liver, and thereby plays an
CC important role in cholesterol homeostasis. First, it is functionally
CC associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it
CC is enriched in circulating HDLs and mediates their uptake by
CC hepatocytes. APOE also plays an important role in lipid transport in
CC the central nervous system, regulating neuron survival and sprouting.
CC {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; AC188244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
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:0031175; P:neuron projection development; 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..322
FT /note="Apolipoprotein E"
FT /id="PRO_0000420993"
FT REPEAT 84..105
FT /note="1"
FT REPEAT 106..127
FT /note="2"
FT REPEAT 128..149
FT /note="3"
FT REPEAT 150..171
FT /note="4"
FT REPEAT 172..193
FT /note="5"
FT REPEAT 194..215
FT /note="6"
FT REPEAT 216..238
FT /note="7"
FT REPEAT 239..260
FT /note="8"
FT REGION 84..260
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 162..172
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 214..295
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 271..322
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 283..295
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 166..169
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 234..241
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 147
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT CARBOHYD 216
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 322 AA; 36710 MW; E733FC960C87998E CRC64;
MKVLWAALLV AFLAGCQGKM EPELEREPEL EREPELHQQA DWQSGQPWEL ALGRFWDYLR
WVQTLSEQVQ EELLSSQVTQ ELTALMDETM KELKAYKSEL EEQLSPVAEE TRARLSKELQ
AAQARLGADM EDVRSRLAXY RSEVQAMLGQ SXDELRARLA SHLRKLRKRL LRDVDDLQKR
LAVYQAGARE GAERGVSAIR ERLVPLVEQG RARAATVGSS LAGQPLQERA QAWGERLRAR
MEEVGSRTRD RLDEVKEQVE EVRAKLEEQA QQMRLQAEAF QARLKSWFEP LVEDMQRQWA
GLVEKVQAAV GASAAPVPGD NH
