P02650 (APOE_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein E
Short name=Apo-E

Gene names

Name:

Apoe

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
Subcellular location	Secreted.
Tissue specificity	Secreted in plasma.
Post-translational modification	Phosphorylation sites are present in the extracellular medium By similarity.
Miscellaneous	The mature protein has no cysteine residues; however, in different allelic variants where cysteine residues replace arginine at positions 155 or 168, binding of Apo-E to cell membrane receptors is decreased. The amino end of this protein is therefore thought to interact with the receptor.
Sequence similarities	Belongs to the apolipoprotein A1/A4/E family.

Ontologies

Keywords
Biological process	Lipid transport Transport
Cellular component	Chylomicron HDL Secreted VLDL
Domain	Repeat Signal
Ligand	Heparin-binding
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara aging Inferred from direct assay PubMed 19809892. Source: RGD artery morphogenesis Inferred from electronic annotation. Source: Compara cGMP-mediated signaling Inferred from electronic annotation. Source: Compara cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to cholesterol Inferred from expression pattern PubMed 21169230. Source: RGD cellular response to growth factor stimulus Inferred from expression pattern PubMed 19713443PubMed 20535563. Source: RGD cellular response to interleukin-1 Inferred from expression pattern PubMed 22171672. Source: RGD cholesterol catabolic process Inferred from electronic annotation. Source: Compara cholesterol efflux Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara chylomicron remnant clearance Inferred from electronic annotation. Source: Compara high-density lipoprotein particle assembly Inferred from electronic annotation. Source: Compara high-density lipoprotein particle clearance Inferred from electronic annotation. Source: Compara high-density lipoprotein particle remodeling Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB lipoprotein biosynthetic process Inferred from electronic annotation. Source: Compara lipoprotein catabolic process Inferred from electronic annotation. Source: Compara lipoprotein metabolic process Inferred from direct assay PubMed 2492020. Source: RGD low-density lipoprotein particle remodeling Inferred from electronic annotation. Source: Compara maintenance of location in cell Inferred from electronic annotation. Source: Compara negative regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara negative regulation of blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara negative regulation of cholesterol biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of endothelial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from direct assay PubMed 17314289. Source: RGD negative regulation of platelet activation Inferred from electronic annotation. Source: Compara nitric oxide mediated signal transduction Inferred from electronic annotation. Source: Compara oligodendrocyte differentiation Inferred from expression pattern PubMed 21972082. Source: RGD peripheral nervous system axon regeneration Inferred from expression pattern PubMed 2120218. Source: RGD phospholipid efflux Inferred from electronic annotation. Source: Compara positive regulation of axon extension Inferred from direct assay PubMed 21040802. Source: RGD positive regulation of cGMP biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of cholesterol efflux Inferred from electronic annotation. Source: Compara positive regulation of cholesterol esterification Inferred from electronic annotation. Source: Compara positive regulation of low-density lipoprotein particle receptor catabolic process Inferred from electronic annotation. Source: Compara positive regulation of membrane protein ectodomain proteolysis Inferred from electronic annotation. Source: Compara positive regulation of nitric-oxide synthase activity Inferred from electronic annotation. Source: Compara receptor-mediated endocytosis Inferred from electronic annotation. Source: Compara regulation of Cdc42 protein signal transduction Inferred from electronic annotation. Source: Compara regulation of gene expression Inferred from electronic annotation. Source: Compara response to dietary excess Inferred from electronic annotation. Source: Compara response to ethanol Inferred from expression pattern PubMed 11839466. Source: RGD response to insulin stimulus Inferred from expression pattern PubMed 22691999. Source: RGD response to oxidative stress Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from expression pattern PubMed 21907828. Source: RGD reverse cholesterol transport Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from electronic annotation. Source: Compara vasodilation Inferred from electronic annotation. Source: Compara very-low-density lipoprotein particle clearance Inferred from electronic annotation. Source: Compara very-low-density lipoprotein particle remodeling Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 11839466PubMed 7806565. Source: RGD chylomicron Inferred from electronic annotation. Source: UniProtKB-KW dendrite Inferred from direct assay PubMed 8875469. Source: RGD extracellular space Inferred from direct assay PubMed 16947119. Source: RGD extrinsic to external side of plasma membrane Inferred from direct assay PubMed 7616121. Source: RGD high-density lipoprotein particle Inferred from electronic annotation. Source: UniProtKB-KW intermediate-density lipoprotein particle Inferred from electronic annotation. Source: Compara late endosome Inferred from direct assay PubMed 7806565. Source: RGD low-density lipoprotein particle Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from direct assay PubMed 8875469. Source: RGD very-low-density lipoprotein particle Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	antioxidant activity Inferred from electronic annotation. Source: Compara beta-amyloid binding Inferred from sequence or structural similarity. Source: UniProtKB cholesterol transporter activity Inferred from electronic annotation. Source: Compara heparin binding Inferred from electronic annotation. Source: UniProtKB-KW hydroxyapatite binding Inferred from direct assay PubMed 21839718. Source: RGD lipid transporter activity Inferred from direct assay PubMed 12482838PubMed 2492020. Source: RGD lipoprotein particle binding Inferred from electronic annotation. Source: Compara metal chelating activity Inferred from electronic annotation. Source: Compara phosphatidylcholine-sterol O-acyltransferase activator activity Inferred from electronic annotation. Source: Compara phospholipid binding Inferred from direct assay PubMed 2492020. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18
	Chain	19 – 312	294	Apolipoprotein E		PRO_0000001996
Regions
	Repeat	72 – 93	22	1
	Repeat	94 – 115	22	2
	Repeat	116 – 137	22	3
	Repeat	138 – 159	22	4
	Repeat	160 – 181	22	5
	Repeat	182 – 203	22	6
	Repeat	204 – 225	22	7
	Repeat	226 – 247	22	8
	Region	72 – 247	176	8 X 22 AA approximate tandem repeats
	Region	150 – 160	11	LDL receptor binding Potential
	Region	154 – 157	4	Heparin-binding By similarity
	Region	221 – 228	8	Heparin-binding By similarity
Experimental info
	Sequence conflict	104	1	A → T in CAA28650. Ref.1
	Sequence conflict	110	1	A → T no nucleotide entry Ref.3
	Sequence conflict	110	1	A → T in AAC60703. Ref.4
	Sequence conflict	141	1	E → D no nucleotide entry Ref.3
	Sequence conflict	141	1	E → D in AAC60703. Ref.4
	Sequence conflict	206 – 213	8	GAGAAQPL → RWRRPAP in CAA28650. Ref.1
	Sequence conflict	206 – 213	8	GAGAAQPL → RWRRPAP no nucleotide entry Ref.3
	Sequence conflict	309 – 310	2	LE → WR no nucleotide entry Ref.3
	Sequence conflict	309 – 310	2	LE → WR in AAC60703. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P02650 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 8180EEE933378D92	FASTA	312	35,753
	10 20 30 40 50 60 MKALWALLLV PLLTGCLAEG ELEVTDQLPG QSDQPWEQAL NRFWDYLRWV QTLSDQVQEE 70 80 90 100 110 120 LQSSQVTQEL TVLMEDTMTE VKAYKKELEE QLGPVAEETR ARLAKEVQAA QARLGADMED 130 140 150 160 170 180 LRNRLGQYRN EVNTMLGQST EELRSRLSTH LRKMRKRLMR DADDLQKRLA VYKAGAQEGA 190 200 210 220 230 240 ERGVSAIRER LGPLVEQGRQ RTANLGAGAA QPLRDRAQAL SDRIRGRLEE VGNQARDRLE 250 260 270 280 290 300 EVREQMEEVR SKMEEQTQQI RLQAEIFQAR IKGWFEPLVE DMQRQWANLM EKIQASVATN 310 SIASTTVPLE NQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide sequence of the gene encoding the rat apolipoprotein E." Fukazawa C., Matsumoto A., Taylor L.M. Nucleic Acids Res. 14:9527-9528(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure and expression of the rat apolipoprotein E gene." Fung W.-P., Howlett G.J., Schreiber G. J. Biol. Chem. 261:13777-13783(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Rat apolipoprotein E mRNA. Cloning and sequencing of double-stranded cDNA." McLean J.W., Fukazawa C., Taylor J.M. J. Biol. Chem. 258:8993-9000(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Secretion by Saccharomyces cerevisiae of rat apolipoprotein E as a fusion to Mucor rennin." Nomura N., Yamada H., Matsubara N., Horinouchi S., Beppu T. Appl. Microbiol. Biotechnol. 42:865-870(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[6]	Lubec G., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 87-100; 114-122; 130-144; 191-199; 202-216; 226-236 AND 262-270, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04979 Genomic DNA. Translation: CAA28650.1. J02582 Genomic DNA. Translation: AAA40755.1. S76779 mRNA. Translation: AAC60703.1. BC086581 mRNA. Translation: AAH86581.1.
IPI	IPI00190701.
PIR	LPRTE. A26189.
RefSeq	NP_001257610.1. NM_001270681.1. NP_001257611.1. NM_001270682.1. NP_001257612.1. NM_001270683.1. NP_001257613.1. NM_001270684.1. NP_620183.2. NM_138828.3.
UniGene	Rn.32351.
3D structure databases
ProteinModelPortal	P02650.
SMR	P02650. Positions 23-195.
ModBase	Search...
Protein-protein interaction databases
IntAct	P02650. 3 interactions.
STRING	10116.ENSRNOP00000050968.
PTM databases
PhosphoSite	P02650.
Proteomic databases
PaxDb	P02650.
PRIDE	P02650.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000041891; ENSRNOP00000050968; ENSRNOG00000018454.
GeneID	25728.
KEGG	rno:25728.
UCSC	RGD:2138. rat.
Organism-specific databases
CTD	348.
RGD	2138. Apoe.
Phylogenomic databases
eggNOG	NOG44867.
GeneTree	ENSGT00530000063081.
HOGENOM	HOG000034006.
HOVERGEN	HBG010582.
InParanoid	P02650.
KO	K04524.
OrthoDB	EOG4GB76S.
Gene expression databases
Genevestigator	P02650.
GermOnline	ENSRNOG00000018454. Rattus norvegicus.
Family and domain databases
InterPro	IPR013326. ApoA. IPR000074. ApoA1_A4_E. [Graphical view]
Pfam	PF01442. Apolipoprotein. 1 hit. [Graphical view]
SUPFAM	SSF47162. SSF47162. 1 hit.
ProtoNet	Search...
Other
NextBio	607845.

Entry information

Entry name

APOE_RAT

Accession

Primary (citable) accession number: P02650

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program