1LYB

CRYSTAL STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN D: IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Membrane Protein Annotation: OPM

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1lyb.1	All beta proteins	Acid proteases	Acid proteases	Pepsin-like	Cathepsin D	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E [auth D]	d1lyb.2	All beta proteins	Acid proteases	Acid proteases	Pepsin-like	Cathepsin D	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1lyb.1	All beta proteins	Acid proteases	Acid proteases	Pepsin-like	Cathepsin D	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth C]	d1lyb.2	All beta proteins	Acid proteases	Acid proteases	Pepsin-like	Cathepsin D	(Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	2.40.70.10	Mainly Beta	Beta Barrel	Cathepsin D, subunit A	domain 1	CATH (4.3.0)
E [auth D]	2.40.70.10	Mainly Beta	Beta Barrel	Cathepsin D, subunit A	domain 1	CATH (4.3.0)
A	2.40.70.10	Mainly Beta	Beta Barrel	Cathepsin D, subunit A	domain 1	CATH (4.3.0)
D [auth C]	2.40.70.10	Mainly Beta	Beta Barrel	Cathepsin D, subunit A	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B, E [auth D]	PF00026	Eukaryotic aspartyl protease (Asp)	Eukaryotic aspartyl protease	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B, E [auth D]	CATHEPSIN D	peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity aspartic-type peptidase activity aspartic-type endopeptidase activity	protein localization regulation of localization establishment of protein localization cellular localization regulation of biological process regulation of cellular process regulation of protein localization regulation of establishment of protein localization biological regulation establishment of localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization regulation of localization establishment of protein localization cellular localization regulation of biological process regulation of cellular process regulation of protein localization regulation of establishment of protein localization biological regulation establishment of localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization cellular process autophagosome assembly catabolic process organelle assembly vacuole organization macroautophagy autophagy autophagosome organization cellular component biogenesis cellular component organization organelle organization cellular component assembly metabolic process cellular component organization or biogenesis process utilizing autophagic mechanism cellular response to nitrogen compound cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling response to peptide hormone positive regulation of biological process regulation of signal transduction insulin receptor signaling pathway regulation of cellular response to insulin stimulus cell surface receptor protein tyrosine kinase signaling pathway cell communication positive regulation of response to stimulus cellular response to endogenous stimulus response to hormone receptor metabolic process signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cellular process cellular response to hormone stimulus positive regulation of cellular response to insulin stimulus regulation of signaling cell surface receptor signaling pathway response to endogenous stimulus regulation of insulin receptor signaling pathway positive regulation of insulin receptor signaling pathway response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound receptor recycling cellular response to chemical stimulus regulation of response to stimulus response to chemical response to insulin regulation of cell communication insulin receptor recycling macromolecule metabolic process cellular response to insulin stimulus positive regulation of signaling positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process programmed cell death antigen processing and presentation of exogenous peptide antigen via MHC class II antigen processing and presentation antigen processing and presentation of peptide or polysaccharide antigen via MHC class II immune system process antigen processing and presentation of peptide antigen via MHC class II antigen processing and presentation of exogenous peptide antigen antigen processing and presentation of peptide antigen antigen processing and presentation of exogenous antigen lipoprotein metabolic process primary metabolic process protein catabolic process protein metabolic process lipoprotein catabolic process macromolecule catabolic process proteolysis insulin catabolic process insulin metabolic process	membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cellular anatomical structure cytoplasmic vesicle organelle cytoplasm vesicle lytic vacuole membrane-enclosed lumen membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cellular anatomical structure cytoplasmic vesicle organelle cytoplasm vesicle lytic vacuole membrane-enclosed lumen vacuolar lumen vacuole lysosomal lumen intracellular organelle lumen organelle lumen lysosome extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix membrane microdomain membrane raft membrane ficolin-1-rich granule endomembrane system ficolin-1-rich granule lumen secretory granule secretory vesicle tertiary granule lumen tertiary granule vacuolar membrane lytic vacuole membrane bounding membrane of organelle lysosomal membrane organelle membrane endosome membrane endosome cytoplasmic vesicle membrane vesicle membrane vesicle lumen cytoplasmic vesicle lumen secretory granule lumen specific granule lumen specific granule endosome lumen
A, D [auth C]	CATHEPSIN D	peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity aspartic-type peptidase activity aspartic-type endopeptidase activity	protein localization regulation of localization establishment of protein localization cellular localization regulation of biological process regulation of cellular process regulation of protein localization regulation of establishment of protein localization biological regulation establishment of localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization regulation of localization establishment of protein localization cellular localization regulation of biological process regulation of cellular process regulation of protein localization regulation of establishment of protein localization biological regulation establishment of localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization cellular process autophagosome assembly catabolic process organelle assembly vacuole organization macroautophagy autophagy autophagosome organization cellular component biogenesis cellular component organization organelle organization cellular component assembly metabolic process cellular component organization or biogenesis process utilizing autophagic mechanism cellular response to nitrogen compound cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling response to peptide hormone positive regulation of biological process regulation of signal transduction insulin receptor signaling pathway regulation of cellular response to insulin stimulus cell surface receptor protein tyrosine kinase signaling pathway cell communication positive regulation of response to stimulus cellular response to endogenous stimulus response to hormone receptor metabolic process signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cellular process cellular response to hormone stimulus positive regulation of cellular response to insulin stimulus regulation of signaling cell surface receptor signaling pathway response to endogenous stimulus regulation of insulin receptor signaling pathway positive regulation of insulin receptor signaling pathway response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound receptor recycling cellular response to chemical stimulus regulation of response to stimulus response to chemical response to insulin regulation of cell communication insulin receptor recycling macromolecule metabolic process cellular response to insulin stimulus positive regulation of signaling positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process programmed cell death antigen processing and presentation of exogenous peptide antigen via MHC class II antigen processing and presentation antigen processing and presentation of peptide or polysaccharide antigen via MHC class II immune system process antigen processing and presentation of peptide antigen via MHC class II antigen processing and presentation of exogenous peptide antigen antigen processing and presentation of peptide antigen antigen processing and presentation of exogenous antigen lipoprotein metabolic process primary metabolic process protein catabolic process protein metabolic process lipoprotein catabolic process macromolecule catabolic process proteolysis insulin catabolic process insulin metabolic process	membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cellular anatomical structure cytoplasmic vesicle organelle cytoplasm vesicle lytic vacuole membrane-enclosed lumen membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cellular anatomical structure cytoplasmic vesicle organelle cytoplasm vesicle lytic vacuole membrane-enclosed lumen vacuolar lumen vacuole lysosomal lumen intracellular organelle lumen organelle lumen lysosome extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix membrane microdomain membrane raft membrane ficolin-1-rich granule endomembrane system ficolin-1-rich granule lumen secretory granule secretory vesicle tertiary granule lumen tertiary granule vacuolar membrane lytic vacuole membrane bounding membrane of organelle lysosomal membrane organelle membrane endosome membrane endosome cytoplasmic vesicle membrane vesicle membrane vesicle lumen cytoplasmic vesicle lumen secretory granule lumen specific granule lumen specific granule endosome lumen
C [auth I], F [auth J]	PEPSTATIN	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B, E [auth D]	IPR001461	Aspartic peptidase A1	Family
B, E [auth D]	IPR033121	Peptidase family A1 domain	Domain
B, E [auth D]	IPR033144	Cathepsin D	Family
B, E [auth D]	IPR021109	Aspartic peptidase domain superfamily	Homologous Superfamily
B, E [auth D]	IPR001969	Aspartic peptidase, active site	Active Site
B, E [auth D]	IPR012848	Aspartic peptidase, N-terminal	Domain
A, D [auth C]	IPR001461	Aspartic peptidase A1	Family
A, D [auth C]	IPR033121	Peptidase family A1 domain	Domain
A, D [auth C]	IPR033144	Cathepsin D	Family
A, D [auth C]	IPR021109	Aspartic peptidase domain superfamily	Homologous Superfamily
A, D [auth C]	IPR001969	Aspartic peptidase, active site	Active Site
A, D [auth C]	IPR012848	Aspartic peptidase, N-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B, E [auth D]	Pharos: P07339	neuronal ceroid lipofuscinosis 10 Alzheimer disease renal cell carcinoma rheumatoid arthritis papillary renal cell carcinoma sarcomatoid renal cell carcinoma Weight Gain neuronal ceroid lipofuscinosis prostate cancer collecting duct carcinoma amyotrophic lateral sclerosis type 1 chromophobe renal cell carcinoma kidney disease lung carcinoma myocardial infarction neuronal ceroid lipofuscinosis 10 Alzheimer disease renal cell carcinoma rheumatoid arthritis papillary renal cell carcinoma sarcomatoid renal cell carcinoma Weight Gain neuronal ceroid lipofuscinosis prostate cancer collecting duct carcinoma amyotrophic lateral sclerosis type 1 chromophobe renal cell carcinoma kidney disease lung carcinoma myocardial infarction neurodegenerative disease osteoarthritis susceptibility 1 renal carcinoma clear cell renal carcinoma diabetes mellitus hepatocellular carcinoma intellectual disability lysosomal storage disease myopathy breast carcinoma subependymal giant cell astrocytoma inborn errors of metabolism invasive ductal breast carcinoma lung cancer MALT lymphoma osteoarthritis ovarian cancer glioblastoma ulcerative colitis inflammatory bowel disease
A, D [auth C]	Pharos: P07339	neuronal ceroid lipofuscinosis 10 Alzheimer disease renal cell carcinoma rheumatoid arthritis papillary renal cell carcinoma sarcomatoid renal cell carcinoma Weight Gain neuronal ceroid lipofuscinosis prostate cancer collecting duct carcinoma amyotrophic lateral sclerosis type 1 chromophobe renal cell carcinoma kidney disease lung carcinoma myocardial infarction neuronal ceroid lipofuscinosis 10 Alzheimer disease renal cell carcinoma rheumatoid arthritis papillary renal cell carcinoma sarcomatoid renal cell carcinoma Weight Gain neuronal ceroid lipofuscinosis prostate cancer collecting duct carcinoma amyotrophic lateral sclerosis type 1 chromophobe renal cell carcinoma kidney disease lung carcinoma myocardial infarction neurodegenerative disease osteoarthritis susceptibility 1 renal carcinoma clear cell renal carcinoma diabetes mellitus hepatocellular carcinoma intellectual disability lysosomal storage disease myopathy breast carcinoma subependymal giant cell astrocytoma inborn errors of metabolism invasive ductal breast carcinoma lung cancer MALT lymphoma osteoarthritis ovarian cancer glioblastoma ulcerative colitis inflammatory bowel disease

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A, B, D [auth C], E [auth D]	OPM	Monotopic/peripheral	All beta monotopic/peripheral	Peptidase clan AA	Eukaryotic aspartyl protease

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.