APOE_BOSMU
ID APOE_BOSMU Reviewed; 316 AA.
AC P0DN41;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 09-DEC-2015, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Apolipoprotein E;
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE;
OS Bos mutus grunniens (Wild yak) (Bos grunniens).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=30521;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=22751099; DOI=10.1038/ng.2343;
RA Qiu Q., Zhang G., Ma T., Qian W., Wang J., Ye Z., Cao C., Hu Q., Kim J.,
RA Larkin D.M., Auvil L., Capitanu B., Ma J., Lewin H.A., Qian X., Lang Y.,
RA Zhou R., Wang L., Wang K., Xia J., Liao S., Pan S., Lu X., Hou H., Wang Y.,
RA Zang X., Yin Y., Ma H., Zhang J., Wang Z., Zhang Y., Zhang D., Yonezawa T.,
RA Hasegawa M., Zhong Y., Liu W., Zhang Y., Huang Z., Zhang S., Long R.,
RA Yang H., Wang J., Lenstra J.A., Cooper D.N., Wu Y., Wang J., Shi P.,
RA Wang J., Liu J.;
RT "The yak genome and adaptation to life at high altitude.";
RL Nat. Genet. 44:946-949(2012).
RN [2]
RP IDENTIFICATION.
RA Puppione D.L.;
RL Unpublished observations (OCT-2015).
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; AGSK01110808; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DN41; -.
DR SMR; P0DN41; -.
DR Ensembl; ENSBGRT00000045611; ENSBGRP00000039312; ENSBGRG00000024723.
DR GeneTree; ENSGT00950000182929; -.
DR Proteomes; UP000694520; Chromosome 20.
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: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; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0071813; F:lipoprotein particle binding; 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: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; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; 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:0010467; P:gene expression; 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:0010877; P:lipid transport involved in lipid storage; IEA:Ensembl.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; ISS:UniProtKB.
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; ISS:UniProtKB.
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; ISS:UniProtKB.
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:0071830; P:triglyceride-rich lipoprotein particle clearance; ISS:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
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..316
FT /note="Apolipoprotein E"
FT /id="PRO_0000435009"
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 209..289
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT REGION 265..316
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 BINDING 161..164
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT BINDING 228..235
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT MOD_RES 142
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 146
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000250|UniProtKB:P02649"
FT CARBOHYD 211
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P02649"
SQ SEQUENCE 316 AA; 36025 MW; 03F710A9C29ABD1E CRC64;
MKVLWVAVVV ALLAGCQADM EGELGPEEPL TTQQPRGKDS QPWEQALGRF WDYLRWVQTL
SDQVQEELLN TQVIQELTAL MEETMKEVKA YKEELEGQLG PMAQETQARV SKELQAAQAR
LGSDMEDLRN RLAQYRSEVQ AMLGQSTEEL RARMASHLRK LRKRLLRDAD DLKKRLAVYQ
AGASEGAERS LSAVRERFGP LVEQGQSRAA TLSTLAGQPL LERAEAWRQK LHGRLEEVGV
RAQDRLDKIR QQLEEVHAKV EEQGNQMRLQ AEAFQARLRS WFEPLVEDMQ RQWAGLVEKV
QLALRPSPTS PPSENH
