ID APOE_CAMDR Reviewed; 317 AA. AC P0DOC3; DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2016, sequence version 1. DT 11-DEC-2019, entry version 11. DE RecName: Full=Apolipoprotein E; DE Short=Apo-E; DE Flags: Precursor; GN Name=APOE; OS Camelus dromedarius (Dromedary) (Arabian camel). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Tylopoda; Camelidae; Camelus. OX NCBI_TaxID=9838; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Fitak R., Mohandesan E., Burger P.A., Jukka C.; RT "The de novo genome assembly and annotation of a female domestic dromedary RT of North African origin."; RL Submitted (DEC-2014) to the EMBL/GenBank/DDBJ databases. RN [2] RP IDENTIFICATION. RA Puppione D.L.; RL Unpublished observations (JUL-2016). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; JWIN01034738; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR SMR; P0DOC3; -. 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..317 FT /note="Apolipoprotein E" FT /id="PRO_0000437471" 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 161..164 FT /note="Heparin-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 228..235 FT /note="Heparin-binding" FT /evidence="ECO:0000250|UniProtKB:P02649" FT REGION 265..317 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 MOD_RES 142 FT /note="Methionine sulfoxide" FT /evidence="ECO:0000250|UniProtKB:P02649" FT CARBOHYD 211 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:P02649" FT CARBOHYD 310 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:P02649" SQ SEQUENCE 317 AA; 36035 MW; 23EF479EC32DFD3E CRC64; MKALWVALVV TLLAGCRAEV EPEPEPEVQL GQEQPEWQGS QPWELALGRL WDYLRWVQTL SDQVQEELLS TQVTQELTAL MEETMKEVKA YKAELEEQLS PVAQETRARL SKELQAAQAR LGTDMEDLRS RLAHYRNEVQ AMLGQTTDEL RNRLASHLRK LRKRLLRDAE DLQKRLAVYR AGAVEGAERS VSALRERLGP LVEQGRLGTA TTSTLGSQPL RERAEAWGQK LRGRLEAVGA RAQDRLDKMR EQLEEVRAKV EEQASQMRLQ AETFQARLKG WFQPLVEDLQ RQWAGLVEKV QQLAVGTTPT PAASKNQ //