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 03-JUL-2019, entry version 9. 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; OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Tylopoda; OC 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 RT dromedary 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 RA Puppione D.L.; RL Unpublished observations (JUL-2016).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 CC lipid particles, that mainly functions in lipoprotein-mediated CC lipid transport between organs via the plasma and interstitial CC fluids. APOE is a core component of plasma lipoproteins and is CC involved in their production, conversion and clearance. CC Apoliproteins are amphipathic molecules that interact both with CC lipids of the lipoprotein particle core and the aqueous CC environment of the plasma. As such, APOE associates with CC chylomicrons, chylomicron remnants, very low density lipoproteins CC (VLDL) and intermediate density lipoproteins (IDL) but shows a CC preferential binding to high-density lipoproteins (HDL). It also CC binds a wide range of cellular receptors including the LDL CC receptor/LDLR and the very low-density lipoprotein receptor/VLDLR CC that mediate the cellular uptake of the APOE-containing CC lipoprotein particles. Finally, APOE has also a heparin-binding CC activity and binds heparan-sulfate proteoglycans on the surface of CC cells, a property that supports the capture and the receptor- CC mediated uptake of APOE-containing lipoproteins by cells. CC {ECO:0000250|UniProtKB:P02649}. CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P02649}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}. CC Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. CC Secreted, extracellular space, extracellular matrix CC {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is CC associated with chylomicrons, chylomicrons remnants, VLDL, LDL and CC HDL lipoproteins. Lipid poor oligomeric APOE is associated with CC the extracellular matrix in a calcium- and heparan-sulfate CC proteoglycans-dependent manner. Lipidation induces the release CC from the extracellular matrix. {ECO:0000250|UniProtKB:P02649}. CC -!- PTM: APOE exists as multiple glycosylated and sialylated CC glycoforms within cells and in plasma. The extent of glycosylation CC and sialylation are tissue and context specific. CC {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 {ECO:0000250|UniProtKB:P02649}. FT CHAIN 19 317 Apolipoprotein E. FT /FTId=PRO_0000437471. FT REPEAT 79 100 1. FT REPEAT 101 122 2. FT REPEAT 123 144 3. FT REPEAT 145 166 4. FT REPEAT 167 188 5. FT REPEAT 189 210 6. FT REPEAT 211 232 7. FT REPEAT 233 254 8. FT REGION 79 254 8 X 22 AA approximate tandem repeats. FT REGION 157 167 LDL and other lipoprotein receptors FT binding. {ECO:0000250|UniProtKB:P02649}. FT REGION 161 164 Heparin-binding. FT {ECO:0000250|UniProtKB:P02649}. FT REGION 209 289 Lipid-binding and lipoprotein FT association. FT {ECO:0000250|UniProtKB:P02649}. FT REGION 228 235 Heparin-binding. FT {ECO:0000250|UniProtKB:P02649}. FT REGION 265 317 Homooligomerization. FT {ECO:0000250|UniProtKB:P02649}. FT REGION 277 289 Specificity for association with VLDL. FT {ECO:0000250|UniProtKB:P02649}. FT MOD_RES 142 142 Methionine sulfoxide. FT {ECO:0000250|UniProtKB:P02649}. FT CARBOHYD 211 211 O-linked (GalNAc...) threonine. FT {ECO:0000250|UniProtKB:P02649}. FT CARBOHYD 310 310 O-linked (GalNAc...) threonine. FT {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 //