BACE1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: BACE1_HUMAN
• UniProt AC: P56817
• Protein Name: Beta-secretase 1
• Gene Name: BACE1
• Organism: Homo sapiens (Human).
• Sequence Length: 501
• Subcellular Localization: Membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network . Endoplasmic reticulum. Endosome . Cell surface. Cytoplasmic vesicle membrane. Membrane raft . Predominantly localized to the later Golgi/trans-Golgi network (TGN) a
• Protein Description: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase..
• Protein Sequence: MAQALPWLLLWMGAGVLPAHGTQHGIRLPLRSGLGGAPLGLRLPRETDEEPEEPGRRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESTLMTIAYVMAAICALFMLPLCLMVCQWRCLRCLRQQHDDFADDISLLK

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
47	Phosphorylation	GLRLPRETDEEPEEP CCCCCCCCCCCCCCC	50.41	28348404
59	Phosphorylation	EEPGRRGSFVEMVDN CCCCCCCCCEEEECC	25.06	28348404
71	Phosphorylation	VDNLRGKSGQGYYVE ECCCCCCCCCCEEEE	38.89	-
83	Phosphorylation	YVEMTVGSPPQTLNI EEEEEECCCCCEEEE	29.13	-
126	Acetylation	STYRDLRKGVYVPYT HHHHHHHCCEEEECC	61.09	17425515
136	Acetylation	YVPYTQGKWEGELGT EEECCCCCCCCCCCC	32.05	7664377
153	N-linked_Glycosylation	VSIPHGPNVTVRANI EECCCCCCCEEEEEE	46.84	UniProtKB CARBOHYD
153	N-linked_Glycosylation	VSIPHGPNVTVRANI EECCCCCCCEEEEEE	46.84	10887202
172	N-linked_Glycosylation	ESDKFFINGSNWEGI CCCCEEECCCCHHHH	42.56	UniProtKB CARBOHYD
172	N-linked_Glycosylation	ESDKFFINGSNWEGI CCCCEEECCCCHHHH	42.56	10887202
223	N-linked_Glycosylation	CGAGFPLNQSEVLAS CCCCCCCCHHHHHHH	43.50	UniProtKB CARBOHYD
223	N-linked_Glycosylation	CGAGFPLNQSEVLAS CCCCCCCCHHHHHHH	43.50	10887202
252	Phosphorylation	YTGSLWYTPIRREWY CCCCCEEEECCCEEE	10.72	-
259	Phosphorylation	TPIRREWYYEVIIVR EECCCEEEEEEEEEE	5.75	25690035
260	Phosphorylation	PIRREWYYEVIIVRV ECCCEEEEEEEEEEE	12.56	-
275	Sumoylation	EINGQDLKMDCKEYN EECCEEEEEEHHHHC	40.77	-
275	Acetylation	EINGQDLKMDCKEYN EECCEEEEEEHHHHC	40.77	17425515
279	Acetylation	QDLKMDCKEYNYDKS EEEEEEHHHHCCCCC	59.99	17425515
281	Phosphorylation	LKMDCKEYNYDKSIV EEEEHHHHCCCCCCC	12.43	29083192
283	Phosphorylation	MDCKEYNYDKSIVDS EEHHHHCCCCCCCCC	24.68	29083192
285	Acetylation	CKEYNYDKSIVDSGT HHHHCCCCCCCCCCC	31.55	17425515
285	Ubiquitination	CKEYNYDKSIVDSGT HHHHCCCCCCCCCCC	31.55	17425515
286	Phosphorylation	KEYNYDKSIVDSGTT HHHCCCCCCCCCCCC	25.58	29083192
290	Phosphorylation	YDKSIVDSGTTNLRL CCCCCCCCCCCCCCC	27.43	29083192
292	Phosphorylation	KSIVDSGTTNLRLPK CCCCCCCCCCCCCCH	19.23	29083192
293	Phosphorylation	SIVDSGTTNLRLPKK CCCCCCCCCCCCCHH	35.46	29083192
299	Acetylation	TTNLRLPKKVFEAAV CCCCCCCHHHHHHHH	67.19	17425515
300	Ubiquitination	TNLRLPKKVFEAAVK CCCCCCHHHHHHHHH	50.66	17425515
300	Acetylation	TNLRLPKKVFEAAVK CCCCCCHHHHHHHHH	50.66	17425515
307	Acetylation	KVFEAAVKSIKAASS HHHHHHHHHHHHCCC	41.56	17425515
308	Phosphorylation	VFEAAVKSIKAASST HHHHHHHHHHHCCCC	23.79	-
354	N-linked_Glycosylation	YLMGEVTNQSFRITI HCCEECCCCEEEEEE	40.45	10887202
354	N-linked_Glycosylation	YLMGEVTNQSFRITI HCCEECCCCEEEEEE	40.45	UniProtKB CARBOHYD
474	S-palmitoylation	ALFMLPLCLMVCQWR HHHHHHHHHHHHHHH	1.86	-
478	S-palmitoylation	LPLCLMVCQWRCLRC HHHHHHHHHHHHHHH	1.30	-
482	S-palmitoylation	LMVCQWRCLRCLRQQ HHHHHHHHHHHHHHH	2.15	-
485	S-palmitoylation	CQWRCLRCLRQQHDD HHHHHHHHHHHHCCC	2.07	-
498	Phosphorylation	DDFADDISLLK---- CCCHHHHHHCC----	34.34	15886016
501	Ubiquitination	ADDISLLK------- HHHHHHCC-------	64.68	-

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
83	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
252	T	Phosphorylation	Kinase	CDK5	Q00535	PSP
498	S	Phosphorylation	Kinase	CSNK1A1	P48729	GPS
498	S	Phosphorylation	Kinase	CSNK1D	P48730	GPS
498	S	Phosphorylation	Kinase	ROCK2	O75116	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	FBXO2	Q9UK22	PMID:20854419
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:25773675

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
126	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
275	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
279	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
285	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
299	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
300	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
307	K	Acetylation	Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307.	17425515
498	S	Phosphorylation	Phosphorylation at Ser-498 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network.	15615712
501	K	ubiquitylation	Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation.	20484053

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of BACE1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GGA1_HUMAN	GGA1	physical	15466887
GGA1_HUMAN	GGA1	physical	14567678
GGA2_HUMAN	GGA2	physical	14567678
GGA3_HUMAN	GGA3	physical	14567678
GGA1_HUMAN	GGA1	physical	15886016
BRI3_HUMAN	BRI3	physical	15606899
KC1D_HUMAN	CSNK1D	physical	25241761
GGA1_HUMAN	GGA1	physical	26053850
GGA2_HUMAN	GGA2	physical	26053850
GGA3_HUMAN	GGA3	physical	26053850
SORT_HUMAN	SORT1	physical	21245145
KCNQ1_HUMAN	KCNQ1	physical	26454161

Drug and Disease Associations

• Kegg Disease
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.