dbPTM

APOE_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	APOE_HUMAN
UniProt AC	P02649
Protein Name	Apolipoprotein E
Gene Name	APOE
Organism	Homo sapiens (Human).
Sequence Length	317
Subcellular Localization	Secreted .
Protein Description	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..
Protein Sequence	MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
26	Phosphorylation	KVEQAVETEPEPELR HHHHHHHCCCCHHHH	50.68	-
26	O-linked_Glycosylation	KVEQAVETEPEPELR HHHHHHHCCCCHHHH	50.68	23234360
36	O-linked_Glycosylation	EPELRQQTEWQSGQR CHHHHHHHHCCCCCC	30.74	55827161
52	O-linked_Glycosylation	ELALGRFWDYLRWVQ HHHHHHHHHHHHHHH	7.62	23234360
52	Phosphorylation	ELALGRFWDYLRWVQ HHHHHHHHHHHHHHH	7.62	23234360
62	O-linked_Glycosylation	LRWVQTLSEQVQEEL HHHHHHHHHHHHHHH	29.39	23234360
93	N-linked_Glycosylation	MKELKAYKSELEEQL HHHHHHHHHHHHHHH	42.17	10452964
93	Glycation	MKELKAYKSELEEQL HHHHHHHHHHHHHHH	42.17	-
101	Phosphorylation	SELEEQLTPVAEETR HHHHHHHHHHHHHHH	18.53	-
108	Sulfoxidation	TPVAEETRARLSKEL HHHHHHHHHHHHHHH	22.46	22918225
127	Phosphorylation	ARLGADMEDVCGRLV HHHCCCHHHHHHHHH	48.08	-
143	Oxidation	YRGEVQAMLGQSTEE HHHHHHHHHCCCHHH	2.12	-
143	Methionine sulfoxide	YRGEVQAMLGQSTEE HHHHHHHHHCCCHHH	2.12	-
147	Phosphorylation	VQAMLGQSTEELRVR HHHHHCCCHHHHHHH	35.67	19838169
148	Phosphorylation	QAMLGQSTEELRVRL HHHHCCCHHHHHHHH	26.12	23025827
173	Phosphorylation	LLRDADDLQKRLAVY HHCCHHHHHHHHHHH	7.14	19824718
175	Acetylation	RDADDLQKRLAVYQA CCHHHHHHHHHHHHH	57.59	30586965
180	Phosphorylation	LQKRLAVYQAGAREG HHHHHHHHHHHHHHH	6.24	21253578
193	Phosphorylation	EGAERGLSAIRERLG HHHHHHHHHHHHHHH	25.19	26434776
206	Phosphorylation	LGPLVEQGRVRAATV HHHHHHCCCHHHHHH	19.28	-
212	O-linked_Glycosylation	QGRVRAATVGSLAGQ CCCHHHHHHHHHCCC	25.15	11701639
212	Phosphorylation	QGRVRAATVGSLAGQ CCCHHHHHHHHHCCC	25.15	26434776
215	O-linked_Glycosylation	VRAATVGSLAGQPLQ HHHHHHHHHCCCCHH	15.65	OGP
215	Phosphorylation	VRAATVGSLAGQPLQ HHHHHHHHHCCCCHH	15.65	28857561
238	O-linked_Glycosylation	RLRARMEEMGSRTRD HHHHHHHHHHHHHHH	39.23	11701639
238	O-linked_Glycosylation	RLRARMEEMGSRTRD HHHHHHHHHHHHHHH	39.23	11701639
241	O-linked_Glycosylation	ARMEEMGSRTRDRLD HHHHHHHHHHHHHHH	29.21	-
241	Phosphorylation	ARMEEMGSRTRDRLD HHHHHHHHHHHHHHH	29.21	20068231
267	Phosphorylation	KLEEQAQQIRLQAEA HHHHHHHHHHHHHHH	26.28	20068231
281	Phosphorylation	AFQARLKSWFEPLVE HHHHHHHHHHHHHHH	41.40	24505115
286	Ubiquitination	LKSWFEPLVEDMQRQ HHHHHHHHHHHHHHH	5.33	-
307	Phosphorylation	KVQAAVGTSAAPVPS HHHHHHCCCCCCCCC	14.48	24505115
307	O-linked_Glycosylation	KVQAAVGTSAAPVPS HHHHHHCCCCCCCCC	14.48	19838169
308	O-linked_Glycosylation	VQAAVGTSAAPVPSD HHHHHCCCCCCCCCC	19.26	55832387
308	Phosphorylation	VQAAVGTSAAPVPSD HHHHHCCCCCCCCCC	19.26	24505115
314	Phosphorylation	TSAAPVPSDNH---- CCCCCCCCCCC----	51.81	15882073
314	O-linked_Glycosylation	TSAAPVPSDNH---- CCCCCCCCCCC----	51.81	50269
333	O-linked_Glycosylation	----------------------- -----------------------		19838169
334	O-linked_Glycosylation	------------------------ ------------------------		20511397
340	O-linked_Glycosylation	------------------------------ ------------------------------		23234360
340	Phosphorylation	------------------------------ ------------------------------		23234360

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
147	S	Phosphorylation	Kinase	FAM20C	Q8IXL6	Uniprot
314	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
314	S	Phosphorylation	Kinase	CK2-FAMILY	-	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
307	T	Glycosylation	19838169
Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308.
308	S	Glycosylation	19838169
Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308.
314	S	Glycosylation	23234360
Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
147	Phosphorylation	156 (9)	C ⇒ R	rs429358	Alzheimer's disease biomarkers Brain imaging Cerebrospinal AB1-42 levels in Alzheimer's disease dementia Lewy body disease Advanced age-related macular degeneration HDL cholesterol Cerebral amyloid deposition (PET imaging) Cerebral amyloid deposition positivity (PET imaging) Cognitive decline (age-related) Blood protein levels Dementia with Lewy bodies Platelet count Red cell distribution width Neuritic plaques or cerebral amyloid angiopathy (pleiotropy) Neurofibrillary tangles or cerebral amyloid angiopathy (pleiotropy) Neuritic plaques or neurofibrillary tangles (pleiotropy) Parental lifespan	21123754 20100581 23419831 25027320 25188341 26691988 25961943 26252872 28078323 28240269 29263008 27863252 29458411 29030599 27029810
175	Acetylation	176 (1)	R ⇒ C	rs7412	Low density lipoprotein cholesterol Total cholesterol levels HDL cholesterol Cholesterol, total LDL cholesterol Lipid metabolism phenotypes Response to statins (LDL cholesterol change)	28548082 28270201 23067351 22286219 22331829 24023260 25961943 27179730 28371326 28334899 27005778 27863252 20838585 28512139 28135244 28714976 29212778 28714975 28753643
180	Phosphorylation	176 (4)	R ⇒ C	rs7412	Low density lipoprotein cholesterol Total cholesterol levels HDL cholesterol Cholesterol, total LDL cholesterol Lipid metabolism phenotypes Response to statins (LDL cholesterol change)	28548082 28270201 23067351 22286219 22331829 24023260 25961943 27179730 28371326 28334899 27005778 27863252 20838585 28512139 28135244 28714976 29212778 28714975 28753643
212	O-linked Glycosylation	202 (10)	R ⇒ C	rs7412	Low density lipoprotein cholesterol Total cholesterol levels HDL cholesterol Cholesterol, total LDL cholesterol Lipid metabolism phenotypes Response to statins (LDL cholesterol change) Lipid traits Ideal cardiovascular health (clinical and behavioural) LDL cholesterol levels Metabolite levels (lipoprotein measures) Reticulocyte fraction of red cells Cardiovascular risk factors Lipoprotein (a) levels Lipoprotein(a) levels adjusted for apolipoprotein(a) isoforms Pulse pressure Immature fraction of reticulocytes Reticulocyte count Alzheimer's disease (late onset) Coronary artery disease Red cell distribution width High light scatter reticulocyte count	28548082 28270201 23067351 22286219 22331829 24023260 25961943 27179730 28371326 28334899 27005778 27863252 20838585 28512139 28135244 28714976 29212778 28714975 28753643
212	Phosphorylation	202 (10)	R ⇒ C	rs7412	Low density lipoprotein cholesterol Total cholesterol levels HDL cholesterol Cholesterol, total LDL cholesterol Lipid metabolism phenotypes Response to statins (LDL cholesterol change) Lipid traits Ideal cardiovascular health (clinical and behavioural) LDL cholesterol levels Metabolite levels (lipoprotein measures) Reticulocyte fraction of red cells Cardiovascular risk factors Lipoprotein (a) levels Lipoprotein(a) levels adjusted for apolipoprotein(a) isoforms Pulse pressure Immature fraction of reticulocytes Reticulocyte count Alzheimer's disease (late onset) Coronary artery disease Red cell distribution width High light scatter reticulocyte count	28548082 28270201 23067351 22286219 22331829 24023260 25961943 27179730 28371326 28334899 27005778 27863252 20838585 28512139 28135244 28714976 29212778 28714975 28753643

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LRP8_HUMAN	LRP8	physical	12950167
PLTP_HUMAN	PLTP	physical	12810820
LRP2_HUMAN	LRP2	physical	7768901
NFM_HUMAN	NEFM	physical	8620924
TAU_HUMAN	MAPT	physical	7566652
LRP1_HUMAN	LRP1	physical	2779654
SET_MOUSE	Set	physical	21289314
GCDH_HUMAN	GCDH	physical	21163940
PDCD4_HUMAN	PDCD4	physical	21163940
APOE_HUMAN	APOE	physical	21163940
TIM29_HUMAN	C19orf52	physical	21163940
CP2CI_HUMAN	CYP2C18	physical	21163940
ELAV1_HUMAN	ELAVL1	physical	21163940
SYFA_HUMAN	FARSA	physical	21163940
FXL12_HUMAN	FBXL12	physical	21163940
IFIT5_HUMAN	IFIT5	physical	21163940
LONM_HUMAN	LONP1	physical	21163940
NOS3_HUMAN	NOS3	physical	21163940
PRAM_HUMAN	PRAM1	physical	21163940
PRDX2_HUMAN	PRDX2	physical	21163940
RHEB_HUMAN	RHEB	physical	21163940
F10A1_HUMAN	ST13	physical	21163940
ACTG_HUMAN	ACTG1	physical	21163940
ANKH_HUMAN	ANKH	physical	21163940
EPN2_HUMAN	EPN2	physical	21163940
FOXG1_HUMAN	FOXG1	physical	21163940
FXYD7_HUMAN	FXYD7	physical	21163940
HTRA1_HUMAN	HTRA1	physical	21163940
IQEC1_HUMAN	IQSEC1	physical	21163940
M1IP1_HUMAN	MID1IP1	physical	21163940
PIMT_HUMAN	PCMT1	physical	21163940
PKHA6_HUMAN	PLEKHA6	physical	21163940
RL4_HUMAN	RPL4	physical	21163940
TYRO3_HUMAN	TYRO3	physical	21163940
ZN558_HUMAN	ZNF558	physical	21163940
ECSIT_HUMAN	ECSIT	physical	21163940
CDC37_HUMAN	CDC37	physical	21163940
ARFG1_HUMAN	ARFGAP1	physical	21988832

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
107741	Hyperlipoproteinemia 3 (HLPP3)
104310	Alzheimer disease 2 (AD2)
269600	Sea-blue histiocyte disease (SBHD)
611771	Lipoprotein glomerulopathy (LPG)
143890	Familial hypercholesterolemia (FH)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00062	Human Serum Albumin
DB00064	Serum albumin iodonated

Regulatory Network of APOE_HUMAN

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Glycation of apolipoprotein E impairs its binding to heparin:identification of the major glycation site."; Shuvaev V.V., Fujii J., Kawasaki Y., Itoh H., Hamaoka R., Barbier A.,Ziegler O., Siest G., Taniguchi N.; Biochim. Biophys. Acta 1454:296-308(1999). Cited for: GLYCATION AT LYS-93, AND MASS SPECTROMETRY.	10452964 [Abstract]
O-linked Glycosylation
Reference	PubMed
"Enrichment of glycopeptides for glycan structure and attachment siteidentification."; Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,Brinkmalm G., Larson G.; Nat. Methods 6:809-811(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-212; THR-307 AND SER-308,STRUCTURE OF CARBOHYDRATES, AND MASS SPECTROMETRY.	19838169 [Abstract]
Phosphorylation
Reference	PubMed
"An initial characterization of the serum phosphoproteome."; Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A.,Liotta L.A., Petricoin E.F. III; J. Proteome Res. 8:5523-5531(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147, TISSUE SPECIFICITY,AND MASS SPECTROMETRY.	19824718 [Abstract]

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