APOE_HETGA
ID APOE_HETGA Reviewed; 299 AA.
AC G5CBM7;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Heterocephalus glaber (Naked mole rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Bathyergidae;
OC Heterocephalus.
OX NCBI_TaxID=10181;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=26763976; DOI=10.1186/s12864-015-2349-8;
RA Bens M., Sahm A., Groth M., Jahn N., Morhart M., Holtze S.,
RA Hildebrandt T.B., Platzer M., Szafranski K.;
RT "FRAMA: from RNA-seq data to annotated mRNA assemblies.";
RL BMC Genomics 17:54-54(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993625; DOI=10.1038/nature10533;
RA Kim E.B., Fang X., Fushan A.A., Huang Z., Lobanov A.V., Han L.,
RA Marino S.M., Sun X., Turanov A.A., Yang P., Yim S.H., Zhao X.,
RA Kasaikina M.V., Stoletzki N., Peng C., Polak P., Xiong Z., Kiezun A.,
RA Zhu Y., Chen Y., Kryukov G.V., Zhang Q., Peshkin L., Yang L., Bronson R.T.,
RA Buffenstein R., Wang B., Han C., Li Q., Chen L., Zhao W., Sunyaev S.R.,
RA Park T.J., Zhang G., Wang J., Gladyshev V.N.;
RT "Genome sequencing reveals insights into physiology and longevity of the
RT naked mole rat.";
RL Nature 479:223-227(2011).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=33336429; DOI=10.1002/lipd.12286;
RA Puppione D.L., Tran D.P., Zenaidee M.A., Charugundla S., Whitelegge J.P.,
RA Buffenstein R.;
RT "Naked Mole-Rat, a Rodent with an Apolipoprotein A-I Dimer.";
RL Lipids 56:269-278(2021).
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 -!- 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; KM486685; AIZ08970.1; -; mRNA.
DR EMBL; JH204773; EHB18938.1; -; Genomic_DNA.
DR RefSeq; NP_001297225.1; NM_001310296.1.
DR RefSeq; XP_004873198.1; XM_004873141.2.
DR AlphaFoldDB; G5CBM7; -.
DR SMR; G5CBM7; -.
DR STRING; 10181.XP_004873198.1; -.
DR GeneID; 101717206; -.
DR KEGG; hgl:101717206; -.
DR CTD; 348; -.
DR eggNOG; ENOG502QVD6; Eukaryota.
DR InParanoid; G5CBM7; -.
DR OMA; WFEPLVQ; -.
DR OrthoDB; 1314660at2759; -.
DR Proteomes; UP000006813; Unassembled WGS sequence.
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; IEA:Ensembl.
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; IEA:UniProtKB-KW.
DR GO; GO:0034363; C:intermediate-density lipoprotein particle; IEA:Ensembl.
DR GO; GO:0034362; C:low-density lipoprotein particle; IEA:Ensembl.
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; IEA:UniProtKB-KW.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0016209; F:antioxidant activity; IEA:Ensembl.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0071813; F:lipoprotein particle binding; IEA:Ensembl.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IEA:Ensembl.
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: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:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0006707; P:cholesterol catabolic process; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0034382; P:chylomicron remnant clearance; IEA:Ensembl.
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:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0010877; P:lipid transport involved in lipid storage; IEA:Ensembl.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; IEA:Ensembl.
DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
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:0034374; P:low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; 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:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; 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:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; 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:1900223; P:positive regulation of amyloid-beta clearance; 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:0042981; P:regulation of apoptotic process; 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:0045088; P:regulation of innate immune response; 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:0002021; P:response to dietary excess; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0043691; P:reverse cholesterol transport; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; IEA:Ensembl.
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 1: Evidence at protein 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..299
FT /note="Apolipoprotein E"
FT /id="PRO_5007914983"
FT REPEAT 74..95
FT /note="1"
FT REPEAT 96..117
FT /note="2"
FT REPEAT 118..139
FT /note="3"
FT REPEAT 140..161
FT /note="4"
FT REPEAT 162..183
FT /note="5"
FT REPEAT 184..205
FT /note="6"
FT REPEAT 206..223
FT /note="7"
FT REPEAT 224..245
FT /note="8"
FT REGION 74..245
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 152..162
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 204..273
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 261..273
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 156..159
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 219..226
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 299 AA; 34422 MW; 06D09E777E264E11 CRC64;
MKALWAVLVV TLLAGCRADV QPELEMQEPA LWQSGQPWEL ALGRFWDYLR WVQTLSDQVQ
EELLNSQVTQ ELTVLMEDTM KEVKAYKNEL EEELGPVAED TKARLSKELQ GAQARLRADM
EEVRNRLAHY SEEMQVMLGQ SPDELRARLG SHLRKLRKRL LRDAEDLQKR LAVYKAGARE
GAERGVSAIR ERLGSLVEQS RVRAALTGQP LRERAQAWGE RLRGRLEEVG GRARDRLDEV
REQMEEVRAK VEEQAEAFQA RLKGWFEPMM EDMRRQWADL IEKVQLAVGA STPVPSEDH
