5LA7 | pdb_00005la7

Crystal structure of human proheparanase, in complex with glucuronic acid configured aziridine probe JJB355

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	(Trans)glycosidases	8051984	3000313	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Glycosyl hydrolase domain-like	8051986	3001528	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	UNK_F_TYPE	e5la7A2	A: beta sandwiches	X: Glycosyl hydrolase domain-like	H: Glycosyl hydrolase domain (From Topology)	T: Glycosyl hydrolase domain	F: UNK_F_TYPE	ECOD (1.6)
A	Glyco_hydro_3	e5la7A1	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: Glyco_hydro_3	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF03662	Glycosyl hydrolase family 79, N-terminal domain (Glyco_hydro_79n)	Glycosyl hydrolase family 79, N-terminal domain	Family of endo-beta-N-glucuronidase, or heparanase. Heparan sulfate proteoglycans (HSPGs) play a key role in the self- assembly, insolubility and barrier properties of basement membranes and extracellular matrices. Hence, cleavage of heparan sulfate ...	Family of endo-beta-N-glucuronidase, or heparanase. Heparan sulfate proteoglycans (HSPGs) play a key role in the self- assembly, insolubility and barrier properties of basement membranes and extracellular matrices. Hence, cleavage of heparan sulfate (HS) affects the integrity and functional state of tissues and thereby fundamental normal and pathological phenomena involving cell migration and response to changes in the extracellular micro-environment. Heparanase degrades HS at specific intra-chain sites. The enzyme is synthesised as a latent approximately 65 kDa protein that is processed at the N-terminus into a highly active approximately 50 kDa form. Experimental evidence suggests that heparanase may facilitate both tumour cell invasion and neovascularization, both critical steps in cancer progression. The enzyme is also involved in cell migration associated with inflammation and autoimmunity [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Heparanase	hydrolase activity, acting on glycosyl bonds hydrolase activity, hydrolyzing O-glycosyl compounds beta-glucuronidase activity hydrolase activity catalytic activity protein binding binding syndecan binding proteoglycan binding carbohydrate derivative binding heparanase activity	cell adhesion cell-matrix adhesion cell-substrate adhesion cellular process carbohydrate derivative metabolic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process proteoglycan metabolic process glycoprotein metabolic process multicellular organismal process regulation of cellular process positive regulation of biological process cell adhesion cell-matrix adhesion cell-substrate adhesion cellular process carbohydrate derivative metabolic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process proteoglycan metabolic process glycoprotein metabolic process multicellular organismal process regulation of cellular process positive regulation of biological process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of vascular endothelial growth factor production regulation of biosynthetic process regulation of biological process biological regulation regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression vascular endothelial growth factor production biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of vascular endothelial growth factor production regulation of macromolecule biosynthetic process positive regulation of cytokine production regulation of metabolic process response to stimulus response to chemical response to antibiotic cellular response to stimulus positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction signaling regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of response to stimulus regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling cell population proliferation positive regulation of cell population proliferation positive regulation of osteoblast proliferation osteoblast proliferation regulation of cell population proliferation regulation of osteoblast proliferation protein localization establishment of protein localization cellular localization nitrogen compound transport transport establishment of localization transmembrane transport localization protein transmembrane transport protein transport cellular macromolecule localization macromolecule localization regulation of developmental process epidermis development molting cycle process regulation of hair cycle positive regulation of developmental process multicellular organism development skin epidermis development hair follicle development anatomical structure development developmental process epithelium development regulation of multicellular organismal development hair cycle animal organ development tissue development positive regulation of hair follicle development skin development molting cycle regulation of hair follicle development hair cycle process endothelial cell differentiation cellular developmental process endothelium development cell development epithelial cell differentiation endothelial cell development epithelial cell development cell differentiation establishment of endothelial barrier wound healing blood vessel morphogenesis tube development angiogenesis involved in wound healing angiogenesis vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis vascular wound healing response to stress anatomical structure formation involved in morphogenesis response to wounding blood vessel development system development carbohydrate derivative catabolic process catabolic process glycoprotein catabolic process heparan sulfate proteoglycan metabolic process protein catabolic process macromolecule catabolic process sulfur compound catabolic process heparan sulfate proteoglycan catabolic process sulfur compound metabolic process proteoglycan catabolic process regulation of body fluid levels positive regulation of coagulation regulation of response to external stimulus positive regulation of blood coagulation regulation of response to wounding regulation of coagulation regulation of response to stress coagulation positive regulation of hemostasis regulation of biological quality regulation of hemostasis positive regulation of response to wounding regulation of blood coagulation hemostasis response to external stimulus blood coagulation positive regulation of wound healing regulation of wound healing heparin proteoglycan metabolic process	membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen lytic vacuole vacuolar lumen vacuole intracellular membrane-bounded organelle lysosomal lumen intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle cytoplasm membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen lytic vacuole vacuolar lumen vacuole intracellular membrane-bounded organelle lysosomal lumen intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle cytoplasm lysosome membrane microdomain membrane raft membrane cell periphery extracellular matrix external encapsulating structure nucleus nucleoplasm nuclear lumen vacuolar membrane lytic vacuole membrane bounding membrane of organelle lysosomal membrane organelle membrane extracellular region vesicle lumen intracellular vesicle cytoplasmic vesicle lumen secretory granule lumen endomembrane system cytoplasmic vesicle specific granule lumen secretory granule secretory vesicle vesicle specific granule extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017853	Glycoside hydrolase superfamily	Homologous Superfamily
A	IPR005199	Glycoside hydrolase, family 79	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q9Y251	IgA glomerulonephritis melanoma Neoplasm Metastasis nephrosis breast carcinoma MALT lymphoma medulloblastoma ovarian cancer adrenal cortex carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Crohn disease subependymal giant cell astrocytoma depressive disorder large cell medulloblastoma major depressive disorder IgA glomerulonephritis melanoma Neoplasm Metastasis nephrosis breast carcinoma MALT lymphoma medulloblastoma ovarian cancer adrenal cortex carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Crohn disease subependymal giant cell astrocytoma depressive disorder large cell medulloblastoma major depressive disorder pancreatic intraductal papillary-mucinous carcinoma breast cancer psoriasis cutaneous lupus erythematosus ulcerative colitis interstitial cystitis malignant glioma malignant pancreatic neoplasm non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm Sjogren syndrome cutaneous melanoma glioblastoma invasive ductal breast carcinoma malignant mesothelioma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.