APOE_NEOSC
ID APOE_NEOSC Reviewed; 330 AA.
AC A0A2Y9GHM3;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Neomonachus schauinslandi (Hawaiian monk seal) (Monachus schauinslandi).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Phocidae; Neomonachus.
OX NCBI_TaxID=29088;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mohr D.W., Scott A.F.;
RT "Improved de novo genome assembly: linked-read sequencing combined with
RT optical mapping produce a high quality mammalian genome at relatively low
RT cost.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (AUG-2019).
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; NINY01000000; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A2Y9GHM3; -.
DR SMR; A0A2Y9GHM3; -.
DR Proteomes; UP000248481; Genome assembly.
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:InterPro.
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-binding; Oxidation; Phosphoprotein; Reference proteome; Repeat;
KW Secreted; Signal; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..330
FT /note="Apolipoprotein E"
FT /id="PRO_0000448370"
FT REPEAT 96..117
FT /note="1"
FT REPEAT 118..139
FT /note="2"
FT REPEAT 140..161
FT /note="3"
FT REPEAT 162..183
FT /note="4"
FT REPEAT 184..205
FT /note="5"
FT REPEAT 206..227
FT /note="6"
FT REPEAT 247..268
FT /note="7"
FT REGION 21..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 96..268
FT /note="7 X 22 AA approximate tandem repeats"
FT REGION 174..184
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 226..303
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 279..330
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 291..303
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT COMPBIAS 26..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 178..181
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 242..249
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 159
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 330 AA; 38091 MW; 530E9917A983ACE5 CRC64;
MKVLWAALVV ALLAGCWADV EPESPLQGKP EPELEPELEP KRELEQEVEA EAGWQAGQPW
ELALARFWDY LRWVQTLSDQ VQEDMLSNQV TQELTTLMEE TMKEIKAYRA ELEEQLGPMA
SETQARVAKE LQAAQARLRS DMEDVRTRLT QYRGEVQAML GQSTEELRAR FASHMRKLRK
RVLRDAEDLQ KRLAVYRAGV REGAERSVSS IRERLWPLLE QARTRHANLA TQPLRERVDA
LGQQLRGRLE EVGSRARSHL DEVREQMEEV QAKMEEQANQ MRQQVEAFQA RLKSWFEPLV
EDMQRQWAGL VEKVQVAVGT SPTTPPLETK
