5JNX

The 6.6 A cryo-EM structure of the full-length human NPC1 in complex with the cleaved glycoprotein of Ebola virus

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
Membrane Protein Annotation: PDBTM
Membrane Protein Annotation: mpstruc

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Frizzled domain-like	8090917	3001950	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)
B [auth C]	Filo_glycop	e5jnxC1	A: a+b complex topology	X: Envelope glycoprotein GP1 (From Topology)	H: Envelope glycoprotein GP1 (From Topology)	T: Envelope glycoprotein GP1	F: Filo_glycop	ECOD (1.6)
D [auth E]	Filo_glycop	e5jnxE1	A: a+b complex topology	X: Envelope glycoprotein GP1 (From Topology)	H: Envelope glycoprotein GP1 (From Topology)	T: Envelope glycoprotein GP1	F: Filo_glycop	ECOD (1.6)
F [auth G]	Filo_glycop	e5jnxG1	A: a+b complex topology	X: Envelope glycoprotein GP1 (From Topology)	H: Envelope glycoprotein GP1 (From Topology)	T: Envelope glycoprotein GP1	F: Filo_glycop	ECOD (1.6)
C [auth D]	Ebola-like_HR1-HR2	e5jnxD1	A: a+b duplicates or obligate multimers	X: Envelope glycoprotein GP2-related (From Topology)	H: Envelope glycoprotein GP2-related (From Topology)	T: Envelope glycoprotein GP2-related	F: Ebola-like_HR1-HR2	ECOD (1.6)
E [auth F]	Ebola-like_HR1-HR2	e5jnxF1	A: a+b duplicates or obligate multimers	X: Envelope glycoprotein GP2-related (From Topology)	H: Envelope glycoprotein GP2-related (From Topology)	T: Envelope glycoprotein GP2-related	F: Ebola-like_HR1-HR2	ECOD (1.6)
G [auth H]	Ebola-like_HR1-HR2	e5jnxH1	A: a+b duplicates or obligate multimers	X: Envelope glycoprotein GP2-related (From Topology)	H: Envelope glycoprotein GP2-related (From Topology)	T: Envelope glycoprotein GP2-related	F: Ebola-like_HR1-HR2	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF02460	Patched family (Patched)	Patched family	-	Family
A	PF16414	Niemann-Pick C1 N terminus (NPC1_N)	Niemann-Pick C1 N terminus	This is the N-terminal domain of Niemann-Pick C1 family proteins. This family of proteins mediates transport of cholesterol from the intestinal lumen to enterocytes. This domain contains a cholesterol-binding pocket [1-2].	Domain
B [auth C], D [auth E], F [auth G]	PF01611	Filovirus glycoprotein (Filo_glycop)	Filovirus glycoprotein	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Niemann-Pick C1 protein	molecular transducer activity transmembrane signaling receptor activity signaling receptor activity protein binding binding virus receptor activity exogenous protein binding sterol binding organic cyclic compound binding alcohol binding steroid binding lipid binding cholesterol binding small molecule binding	response to stimulus response to chemical response to xenobiotic stimulus cellular localization intracellular lipid transport transport organic substance transport lipid localization lipid transport intracellular transport establishment of localization localization macromolecule localization establishment of localization in cell response to stimulus response to chemical response to xenobiotic stimulus cellular localization intracellular lipid transport transport organic substance transport lipid localization lipid transport intracellular transport establishment of localization localization macromolecule localization establishment of localization in cell cellular process cellular catabolic process catabolic process cellular metabolic process autophagy metabolic process process utilizing autophagic mechanism cholesterol transport sterol transport organic hydroxy compound transport cell death programmed cell death cellular response to stimulus response to organic substance response to lipid response to endogenous stimulus cellular response to organic cyclic compound cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to steroid hormone cellular response to lipid cellular response to organic substance cellular response to steroid hormone stimulus response to organic cyclic compound cellular response to hormone stimulus intracellular cholesterol transport intracellular sterol transport intestinal lipid absorption multicellular organismal process digestion system process intestinal absorption digestive system process intestinal cholesterol absorption lipid digestion response to organonitrogen compound response to lipoprotein particle response to nitrogen compound cellular response to low-density lipoprotein particle stimulus cellular response to lipoprotein particle stimulus cholesterol efflux carbohydrate metabolic process glucan metabolic process polysaccharide metabolic process organic substance metabolic process oligosaccharide metabolic process primary metabolic process macromolecule metabolic process cyclodextrin metabolic process adult walking behavior adult locomotory behavior behavior adult behavior locomotory behavior walking behavior biological process involved in interspecies interaction between organisms symbiont entry into host cell viral process symbiont entry into host viral life cycle biological process involved in interaction with host biological process involved in symbiotic interaction regulation of biological process regulation of cellular process regulation of epithelial cell apoptotic process negative regulation of programmed cell death regulation of apoptotic process biological regulation negative regulation of biological process regulation of programmed cell death epithelial cell apoptotic process negative regulation of apoptotic process negative regulation of epithelial cell apoptotic process negative regulation of cellular process apoptotic process developmental process multicellular organism development hepaticobiliary system development gland development animal organ development anatomical structure development liver development system development neurogenesis cellular developmental process cell differentiation nervous system development oxoacid metabolic process steroid metabolic process organic hydroxy compound metabolic process carboxylic acid metabolic process organic acid metabolic process organic cyclic compound metabolic process bile acid metabolic process small molecule metabolic process monocarboxylic acid metabolic process lipid metabolic process membrane organization cellular component organization membrane raft organization cellular component organization or biogenesis import into cell endocytosis vesicle-mediated transport negative regulation of cellular catabolic process macroautophagy regulation of autophagy negative regulation of cellular metabolic process negative regulation of catabolic process negative regulation of metabolic process regulation of cellular metabolic process regulation of catabolic process negative regulation of macroautophagy regulation of macroautophagy negative regulation of autophagy regulation of cellular catabolic process regulation of metabolic process sterol homeostasis chemical homeostasis homeostatic process cholesterol homeostasis lipid homeostasis sterol metabolic process cholesterol metabolic process alcohol metabolic process secondary alcohol metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process cellular biosynthetic process organonitrogen compound biosynthetic process glycoprotein biosynthetic process carbohydrate derivative metabolic process glycoprotein metabolic process protein glycosylation macromolecule biosynthetic process biosynthetic process glycosylation macromolecule modification macromolecule glycosylation organic substance biosynthetic process protein metabolic process protein modification process cholesterol storage lipid storage maintenance of location gene expression vacuolar transport lysosomal transport signaling negative regulation of signaling negative regulation of intracellular signal transduction regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication negative regulation of TORC1 signaling regulation of intracellular signal transduction negative regulation of TOR signaling signal transduction regulation of TORC1 signaling TOR signaling regulation of signaling regulation of TOR signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus regulation of cell communication TORC1 signaling protein localization establishment of protein localization establishment of protein localization to membrane localization within membrane protein localization to membrane cellular macromolecule localization response to metal ion response to cadmium ion response to inorganic substance	membrane cellular anatomical entity membrane-bounded organelle intracellular organelle organelle envelope intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system extracellular exosome extracellular vesicle extracellular organelle membrane cellular anatomical entity membrane-bounded organelle intracellular organelle organelle envelope intracellular anatomical structure organelle nuclear envelope nucleus intracellular membrane-bounded organelle endomembrane system extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle endosome membrane endosome intracellular vesicle late endosome membrane cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane late endosome cytoplasm organelle membrane vacuolar membrane lytic vacuole vacuole lytic vacuole membrane lysosomal membrane lysosome Golgi apparatus perinuclear region of cytoplasm cell periphery plasma membrane membrane microdomain membrane raft endoplasmic reticulum
B [auth C], D [auth E], F [auth G]	Envelope glycoprotein	binding lipid binding	viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated perturbation of host defense response suppression by virus of host tetherin activity response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response biological process involved in interaction with host viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated perturbation of host defense response suppression by virus of host tetherin activity response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response biological process involved in interaction with host response to biotic stimulus biological process involved in symbiotic interaction modulation by symbiont of host process response to host response to external biotic stimulus modulation of process of another organism modulation by virus of host cellular process symbiont-mediated perturbation of host cellular process symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host interferon-mediated signaling pathway cellular process symbiont-mediated perturbation of host signal transduction pathway import into cell receptor-mediated endocytosis of virus by host cell transport viral life cycle establishment of localization vesicle-mediated transport localization symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus virion attachment to host cell receptor-mediated virion attachment to host cell adhesion of symbiont to host cell entry receptor-mediated virion attachment to host cell adhesion of symbiont to host	membrane cellular anatomical entity virion component virion membrane extracellular region viral membrane viral envelope host cell plasma membrane host cellular component host cell part host cell membrane
C [auth D], E [auth F], G [auth H]	Envelope glycoprotein	binding lipid binding	viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated perturbation of host defense response suppression by virus of host tetherin activity response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response biological process involved in interaction with host viral process fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell symbiont-mediated perturbation of host defense response suppression by virus of host tetherin activity response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response biological process involved in interaction with host response to biotic stimulus biological process involved in symbiotic interaction modulation by symbiont of host process response to host response to external biotic stimulus modulation of process of another organism modulation by virus of host cellular process symbiont-mediated perturbation of host cellular process symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host interferon-mediated signaling pathway cellular process symbiont-mediated perturbation of host signal transduction pathway import into cell receptor-mediated endocytosis of virus by host cell transport viral life cycle establishment of localization vesicle-mediated transport localization symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus virion attachment to host cell receptor-mediated virion attachment to host cell adhesion of symbiont to host cell entry receptor-mediated virion attachment to host cell adhesion of symbiont to host	membrane cellular anatomical entity virion component virion membrane extracellular region viral membrane viral envelope host cell plasma membrane host cellular component host cell part host cell membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR032190	Niemann-Pick C1, N-terminal	Domain
A	IPR004765	NPC1-like	Family
A	IPR000731	Sterol-sensing domain	Domain
A	IPR003392	Protein patched/dispatched	Family
B [auth C], D [auth E], F [auth G]	IPR014625	Filoviruses glycoprotein	Family
B [auth C], D [auth E], F [auth G]	IPR002561	Filoviruses glycoprotein, extracellular domain	Domain
C [auth D], E [auth F], G [auth H]	IPR014625	Filoviruses glycoprotein	Family
C [auth D], E [auth F], G [auth H]	IPR002561	Filoviruses glycoprotein, extracellular domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: O15118	Niemann-Pick disease ophthalmoplegia Niemann-Pick disease, type C1 obesity disorder gastrointestinal stromal tumor Ataxia atherosclerosis cirrhosis of liver liver disease brucellosis osteosarcoma sphingolipidosis histiocytosis inborn errors of metabolism large cell medulloblastoma Niemann-Pick disease ophthalmoplegia Niemann-Pick disease, type C1 obesity disorder gastrointestinal stromal tumor Ataxia atherosclerosis cirrhosis of liver liver disease brucellosis osteosarcoma sphingolipidosis histiocytosis inborn errors of metabolism large cell medulloblastoma lysosomal storage disease metabolic syndrome X ovarian cancer Gaucher disease hydrops fetalis intellectual disability adrenal cortex carcinoma leukodystrophy lung cancer malignant pancreatic neoplasm C syndrome non-Langerhans cell histiocytosis psoriasis heart disease tuberculosis arteriosclerosis disorder lung carcinoma medulloblastoma cholestasis Niemann-Pick disease type C Down syndrome

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Chains	External Link	Comment
A, B [auth C], C [auth D], D [auth E], E [auth F] A, B [auth C], C [auth D], D [auth E], E [auth F], F [auth G], G [auth H]	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A, B [auth C], C [auth D], D [auth E], E [auth F] A, B [auth C], C [auth D], D [auth E], E [auth F], F [auth G], G [auth H]	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	Sterol-Sensing Domain (SSD) Proteins	Niemann-Pick C1 protein, full-length

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.