4N6O

Crystal structure of reduced legumain in complex with cystatin E/M

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d4n6ob1	Alpha and beta proteins (a+b)	Cystatin-like	Cystatin/monellin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4n6ob2	Artifacts	Tags	Tags	Tags	C-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Legumain-like	8049299	4006439	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Caspase-like	8104071	3001096	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Cystatin/monellin	8070219	3000441	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	Peptidase_C13	e4n6oA1	A: a/b three-layered sandwiches	X: Caspase-like (From Topology)	H: Caspase-like (From Topology)	T: Caspase-like	F: Peptidase_C13	ECOD (1.6)
B	Cystatin	e4n6oB1	A: a+b two layers	X: Cystatin-like	H: Cystatin/monellin (From Topology)	T: Cystatin/monellin	F: Cystatin	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.1460	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold		CATH (4.3.0)
B	3.10.450.10	Alpha Beta	Roll	Nuclear Transport Factor 2	Chain: A,	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01650	Peptidase C13 family (Peptidase_C13)	Peptidase C13 family	-	Family
B	PF00031	Cystatin domain (Cystatin)	Cystatin domain	Very diverse family. Attempts to define separate sub-families failed. Typically, either the N-terminal or C-terminal end is very divergent. But splitting into two domains would make very short families. All members except Swiss:Q03196 and Swiss:Q1 ...	Very diverse family. Attempts to define separate sub-families failed. Typically, either the N-terminal or C-terminal end is very divergent. But splitting into two domains would make very short families. All members except Swiss:Q03196 and Swiss:Q10993 are found. Pfam:PF00666 are related to this family but have not been included.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	legumain	peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity cytoskeletal protein binding protein binding binding tau protein binding endopeptidase activator activity enzyme regulator activity enzyme activator activity peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity cytoskeletal protein binding protein binding binding tau protein binding endopeptidase activator activity enzyme regulator activity enzyme activator activity peptidase regulator activity molecular function activator activity molecular function regulator activity peptidase activator activity endopeptidase regulator activity	organic substance metabolic process organonitrogen compound metabolic process proteolysis self proteolysis metabolic process primary metabolic process protein metabolic process macromolecule metabolic process activation of cysteine-type endopeptidase activity regulation of catalytic activity cellular biosynthetic process positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of biological process organic substance metabolic process organonitrogen compound metabolic process proteolysis self proteolysis metabolic process primary metabolic process protein metabolic process macromolecule metabolic process activation of cysteine-type endopeptidase activity regulation of catalytic activity cellular biosynthetic process positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of biological process protein maturation regulation of primary metabolic process positive regulation of molecular function positive regulation of metabolic process regulation of proteolysis regulation of endopeptidase activity organic substance biosynthetic process positive regulation of macromolecule metabolic process zymogen activation regulation of cysteine-type endopeptidase activity regulation of biological process cellular metabolic process regulation of protein metabolic process regulation of peptidase activity biological regulation positive regulation of catalytic activity regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of molecular function positive regulation of hydrolase activity biosynthetic process positive regulation of cysteine-type endopeptidase activity regulation of hydrolase activity positive regulation of endopeptidase activity positive regulation of proteolysis protein processing cellular process regulation of metabolic process multicellular organismal process renal system process system process vacuolar protein processing positive regulation of cell communication regulation of cellular process modulation of chemical synaptic transmission signaling cell communication long-term synaptic potentiation synaptic signaling positive regulation of long-term synaptic potentiation regulation of biological quality positive regulation of cellular process regulation of synaptic plasticity trans-synaptic signaling regulation of signaling cell-cell signaling positive regulation of synaptic transmission chemical synaptic transmission regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of long-term synaptic potentiation regulation of cell communication positive regulation of signaling organonitrogen compound catabolic process catabolic process proteolysis involved in protein catabolic process protein catabolic process macromolecule catabolic process organic substance catabolic process 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 behavior learning or memory nervous system process cognition memory neuron apoptotic process negative regulation of neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of neuron apoptotic process developmental process regulation of multicellular organism growth regulation of growth regulation of developmental growth negative regulation of multicellular organism growth regulation of developmental process developmental growth negative regulation of developmental process growth multicellular organism growth negative regulation of developmental growth negative regulation of growth regulation of multicellular organismal process negative regulation of multicellular organismal process cellular response to stimulus cellular response to inorganic substance cellular response to metal ion response to stimulus response to inorganic substance cellular response to chemical stimulus response to metal ion response to chemical cellular response to calcium ion response to calcium ion cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of locomotion regulation of cell motility regulation of response to external stimulus endothelial cell migration positive regulation of chemotaxis positive regulation of cell migration positive regulation of epithelial cell migration positive regulation of response to stimulus tissue migration positive regulation of response to external stimulus taxis ameboidal-type cell migration positive regulation of cell motility regulation of cell migration positive regulation of endothelial cell chemotaxis regulation of endothelial cell migration epithelial cell migration cell migration endothelial cell chemotaxis cell motility locomotion regulation of epithelial cell migration cell chemotaxis chemotaxis regulation of endothelial cell chemotaxis response to external stimulus regulation of chemotaxis epithelium migration regulation of response to stimulus regulation of locomotion positive regulation of endothelial cell migration cellular component organization cell junction organization dendritic spine organization postsynapse organization plasma membrane bounded cell projection organization cell projection organization neuron projection organization synapse organization cellular component organization or biogenesis positive regulation of monocyte chemotaxis regulation of monocyte chemotaxis myeloid leukocyte migration positive regulation of mononuclear cell migration regulation of immune system process regulation of mononuclear cell migration positive regulation of immune system process regulation of leukocyte chemotaxis regulation of leukocyte migration positive regulation of leukocyte migration positive regulation of leukocyte chemotaxis monocyte chemotaxis leukocyte migration mononuclear cell migration leukocyte chemotaxis learning associative learning negative regulation of signaling negative regulation of ERBB signaling pathway regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway negative regulation of cell communication signal transduction enzyme-linked receptor protein signaling pathway regulation of ERBB signaling pathway cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of signal transduction ERBB signaling pathway cellular response to endogenous stimulus response to hepatocyte growth factor cellular response to growth factor stimulus cellular response to hepatocyte growth factor stimulus response to endogenous stimulus response to growth factor negative regulation of cellular metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process positive regulation of cell cycle mitotic cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle cell cycle regulation of cell cycle fat-soluble vitamin metabolic process steroid metabolic process organic hydroxy compound metabolic process vitamin D metabolic process vitamin metabolic process organic cyclic compound metabolic process small molecule metabolic process lipid metabolic process response to pH response to abiotic stimulus response to acidic pH cellular response to nitrogen compound response to organic substance response to organonitrogen compound response to oxygen-containing compound response to nitrogen compound cellular response to amyloid-beta cellular response to oxygen-containing compound cellular response to organonitrogen compound cellular response to organic substance response to amyloid-beta receptor catabolic process cellular catabolic process receptor metabolic process	apical part of cell cellular anatomical entity membrane-bounded organelle intracellular anatomical structure lytic vacuole membrane-enclosed lumen vacuolar lumen vacuole intracellular membrane-bounded organelle lysosomal lumen intracellular organelle lumen intracellular organelle organelle lumen organelle apical part of cell cellular anatomical entity membrane-bounded organelle intracellular anatomical structure lytic vacuole membrane-enclosed lumen vacuolar lumen vacuole intracellular membrane-bounded organelle lysosomal lumen intracellular organelle lumen intracellular organelle organelle lumen organelle cytoplasm lysosome extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle intracellular vesicle endomembrane system endolysosome cytoplasmic vesicle endosome lumen endosome endolysosome lumen perinuclear region of cytoplasm late endosome
B	cystatin-M	enzyme regulator activity molecular function inhibitor activity peptidase regulator activity molecular function regulator activity enzyme inhibitor activity cysteine-type endopeptidase inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity	developmental process epidermis development anatomical structure development tissue development anatomical structure morphogenesis	cell periphery plasma membrane membrane cellular anatomical entity cornified envelope extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR046427	Legumain prodomain superfamily	Homologous Superfamily
A	IPR048501	Legumain, prodomain	Domain
A	IPR001096	Peptidase C13, legumain	Family
A	IPR043577	Asparaginyl endopeptidase	Family
B	IPR000010	Cystatin domain	Domain
B	IPR046350	Cystatin superfamily	Homologous Superfamily
B	IPR018073	Proteinase inhibitor I25, cystatin, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q99538	Liver Cirrhosis, Experimental tuberculosis acute myeloid leukemia breast carcinoma cutaneous lupus erythematosus Duchenne muscular dystrophy limb-girdle muscular dystrophy myopathy primary biliary cholangitis Becker muscular dystrophy chronic obstructive pulmonary disease dermatomyositis glioblastoma ovarian cancer psoriasis Liver Cirrhosis, Experimental tuberculosis acute myeloid leukemia breast carcinoma cutaneous lupus erythematosus Duchenne muscular dystrophy limb-girdle muscular dystrophy myopathy primary biliary cholangitis Becker muscular dystrophy chronic obstructive pulmonary disease dermatomyositis glioblastoma ovarian cancer psoriasis bone Paget disease colorectal cancer diabetes mellitus juvenile dermatomyositis malignant mesothelioma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia
B	Pharos: Q15828	non-small cell lung carcinoma melanoma breast carcinoma prostate cancer atopic eczema esophageal adenocarcinoma Malignant neoplasm of breast bipolar I disorder cutaneous melanoma invasive ductal breast carcinoma malignant pancreatic neoplasm ovarian cancer psoriasis breast cancer ductal breast carcinoma in situ non-small cell lung carcinoma melanoma breast carcinoma prostate cancer atopic eczema esophageal adenocarcinoma Malignant neoplasm of breast bipolar I disorder cutaneous melanoma invasive ductal breast carcinoma malignant pancreatic neoplasm ovarian cancer psoriasis breast cancer ductal breast carcinoma in situ lung adenocarcinoma nasopharyngeal carcinoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A	SNN	Parent Component: ASN RESID: AA0302 , AA0593 PSI-MOD : L-aspartimide MOD:00307 , 2-(2-aminosuccinimidyl)pentanedioic acid (Asn) MOD:01940 , 2-(2-aminosuccinimidyl)pentanedioic acid (Asp) MOD:01941

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.