6SH1

Crystal structure of substrate-free human neprilysin E584D.

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 [auth AAA]	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8035463	3001975	SCOP2B (2022-06-29)
B [auth CCC]	SCOP2B Superfamily	Metalloproteases (zincins), catalytic domain	8035463	3001975	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 [auth AAA]	Peptidase_M13	e6sh1AAA1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M13	ECOD (1.6)
B [auth CCC]	Peptidase_M13	e6sh1CCC1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: Peptidase_M13	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth AAA], B [auth CCC]	PF05649	Peptidase family M13 (Peptidase_M13_N)	Peptidase family M13	-	Family
A [auth AAA], B [auth CCC]	PF01431	Peptidase family M13 (Peptidase_M13)	Peptidase family M13	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth AAA], B [auth CCC]	Neprilysin	ion binding binding anion binding phosphatidylglycerol binding phospholipid binding lipid binding cardiolipin binding small molecule binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity modified amino acid binding ion binding binding anion binding phosphatidylglycerol binding phospholipid binding lipid binding cardiolipin binding small molecule binding peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity endopeptidase activity modified amino acid binding phosphatidylserine binding metalloendopeptidase activity metallopeptidase activity identical protein binding protein binding protein homodimerization activity protein dimerization activity oligopeptidase activity exopeptidase activity peptide binding cation binding transition metal ion binding zinc ion binding metal ion binding	multicellular organismal process catabolic process amyloid-beta metabolic process amyloid-beta clearance by cellular catabolic process metabolic process cellular process amide metabolic process amyloid-beta clearance developmental process placenta development animal organ development anatomical structure development replicative senescence primary metabolic process multicellular organismal process catabolic process amyloid-beta metabolic process amyloid-beta clearance by cellular catabolic process metabolic process cellular process amide metabolic process amyloid-beta clearance developmental process placenta development animal organ development anatomical structure development replicative senescence primary metabolic process protein catabolic process protein metabolic process macromolecule metabolic process macromolecule catabolic process cellular catabolic process neuropeptide catabolic process substance P catabolic process peptide metabolic process peptide catabolic process creatinine metabolic process small molecule metabolic process lactam metabolic process cellular response to stimulus response to light stimulus response to stimulus cellular response to radiation response to UV response to UV-B cellular response to environmental stimulus cellular response to UV-B cellular response to light stimulus response to radiation response to abiotic stimulus cellular response to abiotic stimulus cellular response to UV positive regulation of nervous system development regulation of cellular process regulation of developmental process cellular developmental process positive regulation of biological process cell development regulation of cell differentiation regulation of neurogenesis regulation of cell development regulation of nervous system development positive regulation of developmental process multicellular organism development neurogenesis positive regulation of cell differentiation cell differentiation positive regulation of neurogenesis regulation of multicellular organismal process positive regulation of cellular process system development regulation of multicellular organismal development regulation of biological process biological regulation positive regulation of cell development nervous system development positive regulation of multicellular organismal process bradykinin catabolic process kidney development renal system development response to hormone response to endogenous stimulus response to chemical response to estrogen positive regulation of cell communication 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 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 tube development respiratory tube development lung development respiratory system development gene expression macromolecule biosynthetic process protein maturation biosynthetic process proteolysis protein processing signaling receptor ligand precursor processing neuropeptide processing behavior system process learning or memory nervous system process cognition regulation of hormone levels hormone metabolic process hormone catabolic process sensory perception sensory perception of pain cellular response to UV-A response to UV-A response to peptide response to cytokine cellular response to cytokine stimulus	cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cluster of actin-based cell projections brush border somatodendritic compartment cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cluster of actin-based cell projections brush border somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection intracellular anatomical structure cytoplasm Golgi apparatus subcompartment Golgi apparatus organelle subcompartment intracellular membrane-bounded organelle endomembrane system intracellular organelle trans-Golgi network cell body neuronal cell body axon transport vesicle synapse intracellular vesicle presynapse cytoplasmic vesicle synaptic vesicle cell junction secretory vesicle exocytic vesicle anchoring junction focal adhesion cell-substrate junction cell surface cell periphery plasma membrane membrane microdomain membrane raft early endosome endosome neuron projection terminus cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane secretory granule organelle membrane secretory granule membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth AAA], B [auth CCC]	IPR018497	Peptidase M13, C-terminal domain	Domain
A [auth AAA], B [auth CCC]	IPR008753	Peptidase M13, N-terminal domain	Domain
A [auth AAA], B [auth CCC]	IPR000718	Peptidase M13	Family
A [auth AAA], B [auth CCC]	IPR024079	Metallopeptidase, catalytic domain superfamily	Homologous Superfamily
A [auth AAA], B [auth CCC]	IPR042089	Peptidase M13, domain 2	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth AAA], B [auth CCC]	Pharos: P08473	Charcot-Marie-Tooth disease autosomal dominant cerebellar ataxia Charcot-Marie-Tooth disease axonal type 2T breast carcinoma prostate cancer kidney failure diabetic autonomic neuropathy diabetic neuropathy Liver Cirrhosis, Experimental breast cancer cryopyrin-associated periodic syndrome peripheral neuropathy diabetic polyneuropathy spinocerebellar ataxia 43 periodontitis Charcot-Marie-Tooth disease autosomal dominant cerebellar ataxia Charcot-Marie-Tooth disease axonal type 2T breast carcinoma prostate cancer kidney failure diabetic autonomic neuropathy diabetic neuropathy Liver Cirrhosis, Experimental breast cancer cryopyrin-associated periodic syndrome peripheral neuropathy diabetic polyneuropathy spinocerebellar ataxia 43 periodontitis ductal breast carcinoma in situ spinocerebellar ataxia type 1 hereditary ataxia spinocerebellar ataxia type 5 idiopathic membranous glomerulonephritis spondyloarthropathy acute diarrhea ulcerative colitis lung cancer cancer lymphatic system disease membranous glomerulonephritis cystic fibrosis myopathy osteosarcoma peripheral nervous system disease facioscapulohumeral muscular dystrophy spinocerebellar ataxia type 2 spinocerebellar ataxia type 6 invasive ductal breast carcinoma acute myeloid leukemia lung carcinoma cerebellar ataxia malignant colon neoplasm motor peripheral neuropathy neurodegenerative disease pancreatic intraductal papillary-mucinous carcinoma familial cold autoinflammatory syndrome spinocerebellar ataxia type 4 hypertensive disorder spinocerebellar ataxia type 7 kidney disease transitional cell carcinoma lung adenocarcinoma malignant mesothelioma cutaneous lupus erythematosus Muckle-Wells syndrome non-small cell lung carcinoma

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.