APOE_PHYMC
ID APOE_PHYMC Reviewed; 317 AA.
AC P0DMM0;
DT 03-SEP-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-SEP-2014, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Physeter macrocephalus (Sperm whale) (Physeter catodon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Physeteridae; Physeter.
OX NCBI_TaxID=9755;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Walter R., Wise J., Warren W., Wilson R.K.;
RL Submitted (SEP-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (JUN-2014).
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; AWZP01003783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_007101327.1; XM_007101265.1.
DR AlphaFoldDB; P0DMM0; -.
DR SMR; P0DMM0; -.
DR STRING; 9755.ENSPCTP00005026101; -.
DR Ensembl; ENSPCTT00005028741; ENSPCTP00005026101; ENSPCTG00005018722.
DR GeneID; 102995691; -.
DR KEGG; pcad:102995691; -.
DR CTD; 348; -.
DR OrthoDB; 1314660at2759; -.
DR Proteomes; UP000248484; Chromosome 17.
DR GO; GO:0042627; C:chylomicron; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
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:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0043083; C:synaptic cleft; IEA:Ensembl.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0016209; F:antioxidant activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
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:0005319; F:lipid transporter activity; IEA:Ensembl.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:UniProtKB.
DR GO; GO:0046911; F:metal chelating activity; IEA:Ensembl.
DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IEA:Ensembl.
DR GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0048156; F:tau protein binding; IEA:Ensembl.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; IEA:Ensembl.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; IEA:Ensembl.
DR GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0034382; P:chylomicron remnant clearance; ISS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; ISS:UniProtKB.
DR GO; GO:0034384; P:high-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IEA:Ensembl.
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:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0015909; P:long-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IEA:Ensembl.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0010544; P:negative regulation of platelet activation; IEA:Ensembl.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IEA:Ensembl.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0033700; P:phospholipid efflux; IEA:Ensembl.
DR GO; GO:0044794; P:positive regulation by host of viral process; IEA:Ensembl.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IEA:Ensembl.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:1905920; P:positive regulation of CoA-transferase activity; IEA:Ensembl.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IEA:Ensembl.
DR GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:1905855; P:positive regulation of heparan sulfate binding; IEA:Ensembl.
DR GO; GO:1905860; P:positive regulation of heparan sulfate proteoglycan binding; IEA:Ensembl.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IEA:Ensembl.
DR GO; GO:1903002; P:positive regulation of lipid transport across blood-brain barrier; IEA:Ensembl.
DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; IEA:Ensembl.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IEA:Ensembl.
DR GO; GO:1902995; P:positive regulation of phospholipid efflux; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0017038; P:protein import; IEA:Ensembl.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IEA:Ensembl.
DR GO; GO:1905906; P:regulation of amyloid fibril formation; IEA:Ensembl.
DR GO; GO:1900221; P:regulation of amyloid-beta clearance; IEA:Ensembl.
DR GO; GO:2000822; P:regulation of behavioral fear response; IEA:Ensembl.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IEA:Ensembl.
DR GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0061771; P:response to caloric restriction; IEA:Ensembl.
DR GO; GO:0043691; P:reverse cholesterol transport; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
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 GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0019068; P:virion assembly; IEA:Ensembl.
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;
KW Reference proteome; Repeat; Secreted; Signal; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..317
FT /note="Apolipoprotein E"
FT /id="PRO_0000429978"
FT REPEAT 80..101
FT /note="1"
FT REPEAT 102..123
FT /note="2"
FT REPEAT 124..145
FT /note="3"
FT REPEAT 146..167
FT /note="4"
FT REPEAT 168..189
FT /note="5"
FT REPEAT 190..211
FT /note="6"
FT REPEAT 212..233
FT /note="7"
FT REPEAT 234..255
FT /note="8"
FT REGION 80..255
FT /note="8 X 22 AA approximate tandem repeats"
FT /evidence="ECO:0000250"
FT REGION 158..168
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 210..290
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 266..317
FT /note="Homooligomerization"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 278..290
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 162..165
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 229..236
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 143
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
SQ SEQUENCE 317 AA; 36291 MW; 7C946D63BA65D898 CRC64;
MKVLWVALVI TLLAGCQAEE VKPAPEPEVQ LGQEWPGWQG SQPWEQALGR FWDYLRWVQT
LSDQVQEELL STQVIQELTV LMDETMKEVK AYREELEEQL GPVAQETQAR VSKELQAAQA
RLASDMQDVR GRLAQYRSEV QAMMGHTTDE LRDRLASHLR KLRKRLLRDA EDLQKRLAVY
RAGALEGSER SVSAIRERLG PLVEQGRARA ATVGTLASQT LRERAEAWHQ KLRGRVEEMG
TQARDHLEEM REQLDEVRAK VEEQGTQMRL QAEAFQARLK SWFEPLVEDM QRQWAGLVEK
VQLAMATSST SAPSENH
