APOE_RABIT
ID APOE_RABIT Reviewed; 311 AA.
AC P18287;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3632744; DOI=10.1016/0021-9150(87)90187-0;
RA Hao Q.L., Yamin T.T., Pan T.C., Chen S.L., Chen B.S., Kroon P.A.,
RA Chao Y.S.;
RT "Isolation and characterization of a full-length rabbit apolipoprotein E
RT cDNA.";
RL Atherosclerosis 66:125-130(1987).
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; M36603; AAA31164.1; -; mRNA.
DR PIR; A45951; A45951.
DR RefSeq; NP_001076112.1; NM_001082643.1.
DR AlphaFoldDB; P18287; -.
DR SMR; P18287; -.
DR GeneID; 100009337; -.
DR KEGG; ocu:100009337; -.
DR CTD; 348; -.
DR InParanoid; P18287; -.
DR OrthoDB; 1314660at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:ARUK-UCL.
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:0042277; F:peptide binding; IPI:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ARUK-UCL.
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: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 2: Evidence at transcript level;
KW Chylomicron; Extracellular matrix; Glycoprotein; HDL; Heparin-binding;
KW Lipid transport; Lipid-binding; Oxidation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..311
FT /note="Apolipoprotein E"
FT /id="PRO_0000001995"
FT REPEAT 74..95
FT /note="1"
FT REPEAT 96..116
FT /note="2"
FT REPEAT 117..138
FT /note="3"
FT REPEAT 139..160
FT /note="4"
FT REPEAT 161..182
FT /note="5"
FT REPEAT 183..204
FT /note="6"
FT REPEAT 205..226
FT /note="7"
FT REPEAT 227..248
FT /note="8"
FT REGION 74..248
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 151..161
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 203..283
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 259..311
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 155..158
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"
FT MOD_RES 136
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT CARBOHYD 205
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:Q03247"
SQ SEQUENCE 311 AA; 35497 MW; 3E1566BC1AAE2655 CRC64;
MKVWWAVLAA AILAGCRAQT EQEVEVPEQA RWKAGQPWEL ALGRFWDYLR WVQSLSDQVQ
EELLSSQVTQ ELTMLMEETM KEVKAYKSEL EEQLSPMAQE HRARLSKELQ VAGALEADME
DVCNRLAQYR GEAQAMLGQS TEELARAFSS HLRKLRKRLL RDAEDLQKRM AVYGAGAREG
AERGVSAVRE RLGSRLERGR LRVATVGTLA GRPLRERAQA WGERLRGHLE EVGSRARDRL
NEVREQVEEV RVKVEEQAPQ MRLQAEAFQA RLKSWFEPLV EDMQRQWAGL VEKLQAAMPS
KAPAAAPIEN Q
