HPSE_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HPSE_HUMAN
• UniProt AC: Q9Y251
• Protein Name: Heparanase
• Gene Name: HPSE
• Organism: Homo sapiens (Human).
• Sequence Length: 543
• Subcellular Localization: Lysosome membrane; Peripheral membrane protein. Secreted. Nucleus. Proheparanase is secreted via vesicles of the Golgi. Interacts with cell membrane heparan sulfate proteoglycans (HSPGs). Endocytosed and accumulates in endosomes. Transferred to lysos
• Protein Description: Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis..
• Protein Sequence: MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFFTQEPLHLVSPSFLSVTIDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFLIFDPKKESTFEERSYWQSQVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKFKNSTYSRSSVDVLYTFANCSGLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNEPNSFLKKADIFINGSQLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTAKMLKSFLKAGGEVIDSVTWHHYYLNGRTATKEDFLNPDVLDIFISSVQKVFQVVESTRPGKKVWLGETSSAYGGGAPLLSDTFAAGFMWLDKLGLSARMGIEVVMRQVFFGAGNYHLVDENFDPLPDYWLSLLFKKLVGTKVLMASVQGSKRRKLRVYLHCTNTDNPRYKEGDLTLYAINLHNVTKYLRLPYPFSNKQVDKYLLRPLGPHGLLSKSVQLNGLTLKMVDDQTLPPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVAACI

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
98	Acetylation	YLRFGGTKTDFLIFD HHHCCCCCCCEEEEC	49.74	20167786
99	Phosphorylation	LRFGGTKTDFLIFDP HHCCCCCCCEEEECC	31.64	20068231
116	Phosphorylation	ESTFEERSYWQSQVN CCCHHHHHHHHHHHC	33.72	29449344
117	Phosphorylation	STFEERSYWQSQVNQ CCHHHHHHHHHHHCH	17.43	29449344
120	Phosphorylation	EERSYWQSQVNQDIC HHHHHHHHHHCHHHH	23.19	29449344
129	Phosphorylation	VNQDICKYGSIPPDV HCHHHHHHCCCCCCH	16.22	29449344
131	Phosphorylation	QDICKYGSIPPDVEE HHHHHHCCCCCCHHH	28.91	29449344
156	Phosphorylation	QLLLREHYQKKFKNS HHHHHHHHHHHCCCC	19.78	21831044
162	N-linked_Glycosylation	HYQKKFKNSTYSRSS HHHHHCCCCCCCCCC	42.59	14573609
162	N-linked_Glycosylation	HYQKKFKNSTYSRSS HHHHHCCCCCCCCCC	42.59	14573609
165	Phosphorylation	KKFKNSTYSRSSVDV HHCCCCCCCCCCCCH	11.25	-
178	N-linked_Glycosylation	DVLYTFANCSGLDLI CHHHHCCCCCCHHHH	19.12	14573609
178	N-linked_Glycosylation	DVLYTFANCSGLDLI CHHHHCCCCCCHHHH	19.12	14573609
200	N-linked_Glycosylation	RTADLQWNSSNAQLL HHCCCCCCCCCHHHH	23.69	14573609
204	Ubiquitination	LQWNSSNAQLLLDYC CCCCCCCHHHHHHHH	11.89	29967540
217	N-linked_Glycosylation	YCSSKGYNISWELGN HHHCCCCCEEEECCC	30.41	16263699
228	Phosphorylation	ELGNEPNSFLKKADI ECCCCCCCHHHHCCE	42.55	24719451
238	N-linked_Glycosylation	KKADIFINGSQLGED HHCCEEECCCCCCHH	33.06	14573609
238	N-linked_Glycosylation	KKADIFINGSQLGED HHCCEEECCCCCCHH	33.06	14573609
262	Ubiquitination	KSTFKNAKLYGPDVG HHCCCCCCCCCCCCC	52.19	29967540
264	Phosphorylation	TFKNAKLYGPDVGQP CCCCCCCCCCCCCCC	26.38	24114839
281	Phosphorylation	KTAKMLKSFLKAGGE HHHHHHHHHHHHCCE	31.67	24719451
332	Phosphorylation	KVFQVVESTRPGKKV HHHHHHHCCCCCCEE	20.36	-
333	Phosphorylation	VFQVVESTRPGKKVW HHHHHHCCCCCCEEE	27.64	-
348	Phosphorylation	LGETSSAYGGGAPLL EEECCCCCCCCCCCC	20.46	-
422	Phosphorylation	GTKVLMASVQGSKRR CCEEEEEECCCCCCC	10.87	28060719
426	Phosphorylation	LMASVQGSKRRKLRV EEEECCCCCCCCEEE	13.09	28060719
427	Acetylation	MASVQGSKRRKLRVY EEECCCCCCCCEEEE	64.15	7671115
459	N-linked_Glycosylation	LYAINLHNVTKYLRL EEEEECCCHHEEECC	46.44	14573609
459	N-linked_Glycosylation	LYAINLHNVTKYLRL EEEEECCCHHEEECC	46.44	14573609
478	Phosphorylation	SNKQVDKYLLRPLGP CCHHHHHHHCCCCCC	13.40	22817900
490	Phosphorylation	LGPHGLLSKSVQLNG CCCCCHHCCEEEECC	28.11	24719451
507	Phosphorylation	LKMVDDQTLPPLMEK EEEECCCCCCCCCCC	48.50	20068231
520	Phosphorylation	EKPLRPGSSLGLPAF CCCCCCCCCCCCCCE	25.68	28270605
521	Phosphorylation	KPLRPGSSLGLPAFS CCCCCCCCCCCCCEE	32.16	28270605
528	Phosphorylation	SLGLPAFSYSFFVIR CCCCCCEEEEEEEEE	23.21	28270605
529	Phosphorylation	LGLPAFSYSFFVIRN CCCCCEEEEEEEEEC	11.75	28270605
530	Phosphorylation	GLPAFSYSFFVIRNA CCCCEEEEEEEEECC	15.83	28270605

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

Oops, there are no upstream regulatory protein records of HPSE_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of HPSE_HUMAN !!

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HPSE_HUMAN	HPSE	physical	12927802
DNJA4_HUMAN	DNAJA4	physical	28514442
OS9_HUMAN	OS9	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB06779: Dalteparin
• DB01109: Heparin

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry.";
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
J. Proteome Res. 8:651-661(2009).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-217 AND ASN-238, AND MASSSPECTROMETRY.
PubMed: 19159218

"Elucidation of N-glycosylation sites on human platelet proteins: aglycoproteomic approach.";
Lewandrowski U., Moebius J., Walter U., Sickmann A.;
Mol. Cell. Proteomics 5:226-233(2006).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-217, AND MASSSPECTROMETRY.
PubMed: 16263699

"Secretion of heparanase protein is regulated by glycosylation inhuman tumor cell lines.";
Simizu S., Ishida K., Wierzba M.K., Osada H.;
J. Biol. Chem. 279:2697-2703(2004).
Cited for: GLYCOSYLATION AT ASN-162; ASN-178; ASN-200; ASN-217; ASN-238 ANDASN-459, AND MUTAGENESIS OF ASN-162; ASN-178; ASN-200; ASN-217;ASN-238 AND ASN-459.
PubMed: 14573609