6N4R

CryoEM structure of Nav1.7 VSD2 (deactived state) in complex with the gating modifier toxin ProTx2

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
IMGT Antibody Annotation
SAbDab Antibody Annotation
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Membrane Protein Annotation: OPM
Membrane Protein Annotation: PDBTM
Membrane Protein Annotation: MemProtMD
Membrane Protein Annotation: mpstruc

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
D [auth E]	SCOP2B Superfamily	omega toxin-like	8082346	3000255	SCOP2B (2022-06-29)
E [auth F]	SCOP2B Superfamily	omega toxin-like	8082346	3000255	SCOP2B (2022-06-29)
F [auth G]	SCOP2B Superfamily	omega toxin-like	8082346	3000255	SCOP2B (2022-06-29)
G [auth H]	SCOP2B Superfamily	omega toxin-like	8082346	3000255	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 B]	Ion_trans	e6n4rB1	A: alpha complex topology	X: Voltage-gated ion channels (From Topology)	H: Voltage-gated ion channels (From Topology)	T: Voltage-gated ion channels	F: Ion_trans	ECOD (1.6)
B [auth C]	Ion_trans	e6n4rC1	A: alpha complex topology	X: Voltage-gated ion channels (From Topology)	H: Voltage-gated ion channels (From Topology)	T: Voltage-gated ion channels	F: Ion_trans	ECOD (1.6)
C [auth D]	Ion_trans	e6n4rD1	A: alpha complex topology	X: Voltage-gated ion channels (From Topology)	H: Voltage-gated ion channels (From Topology)	T: Voltage-gated ion channels	F: Ion_trans	ECOD (1.6)
L [auth A]	Ion_trans	e6n4rA1	A: alpha complex topology	X: Voltage-gated ion channels (From Topology)	H: Voltage-gated ion channels (From Topology)	T: Voltage-gated ion channels	F: Ion_trans	ECOD (1.6)
D [auth E]	Toxin_12	e6n4rE1	A: few secondary structure elements	X: omega toxin-like	H: omega toxin-related	T: omega toxin-related	F: Toxin_12	ECOD (1.6)
E [auth F]	Toxin_12	e6n4rF1	A: few secondary structure elements	X: omega toxin-like	H: omega toxin-related	T: omega toxin-related	F: Toxin_12	ECOD (1.6)
F [auth G]	Toxin_12	e6n4rG1	A: few secondary structure elements	X: omega toxin-like	H: omega toxin-related	T: omega toxin-related	F: Toxin_12	ECOD (1.6)
G [auth H]	Toxin_12	e6n4rH1	A: few secondary structure elements	X: omega toxin-like	H: omega toxin-related	T: omega toxin-related	F: Toxin_12	ECOD (1.6)
H [auth I]	C1-set_4	e6n4rI2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
H [auth I]	V-set	e6n4rI1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
J [auth K]	C1-set_4	e6n4rK2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
J [auth K]	V-set	e6n4rK1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
I [auth J]	C1-set_1	e6n4rJ2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
I [auth J]	V-set_12	e6n4rJ1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_12	ECOD (1.6)
K [auth L]	C1-set_1	e6n4rL1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
K [auth L]	V-set_12	e6n4rL2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_12	ECOD (1.6)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
H [auth I], J [auth K]	Antibody Fab Fragment	L-KAPPA	Mus musculus (house mouse)	IGKV4-5301, IGKJ102, IGKC01, IGKC02	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-2A_KAPPA	IMGT (202448-0)
I [auth J], K [auth L]	Antibody Fab Fragment	VH-CH1	Mus musculus (house mouse)	IGHV5-9-301, IGHJ401, IGHG2A01, IGHG2A02	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-2A_KAPPA	IMGT (202448-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
H [auth I], J [auth K]	Light Chain	IGKV4	Kappa	nav1.7 vsd2-navab chimera \| nav1.7 vsd2-navab chimera \| beta/omega-theraphotoxin-tp2a	SAbDab (2024-12-06)
I [auth J], K [auth L]	Heavy Chain	IGHV5	-	nav1.7 vsd2-navab chimera \| nav1.7 vsd2-navab chimera \| beta/omega-theraphotoxin-tp2a	SAbDab (2024-12-06)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth B], B [auth C], C [auth D], L [auth A]	PF08016	Polycystin cation channel (PKD_channel)	Polycystin cation channel	-	Family
A [auth B], B [auth C], C [auth D], L [auth A]	PF00520	Ion transport protein (Ion_trans)	Ion transport protein	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth B], B [auth C], C [auth D], L [auth A]	Nav1.7 VSD2-NavAb chimera	monoatomic cation transmembrane transporter activity voltage-gated sodium channel activity monoatomic ion channel activity sodium channel activity sodium ion transmembrane transporter activity monoatomic cation channel activity passive transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity monoatomic cation transmembrane transporter activity voltage-gated sodium channel activity monoatomic ion channel activity sodium channel activity sodium ion transmembrane transporter activity monoatomic cation channel activity passive transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity cation binding ion binding binding metal ion binding small molecule binding identical protein binding protein binding	heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction biological regulation action potential actin filament-based movement cardiac muscle contraction muscle contraction muscle system process striated muscle contraction circulatory system process actin filament-based process heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction biological regulation action potential actin filament-based movement cardiac muscle contraction muscle contraction muscle system process striated muscle contraction circulatory system process actin filament-based process cellular process regulation of biological quality actin-mediated cell contraction heart contraction cardiac muscle cell action potential blood circulation regulation of membrane potential rhythmic process circadian rhythm response to stimulus response to chemical response to toxic substance behavior response to stress multicellular organismal response to stress response to pain behavioral response to pain transport monoatomic ion transmembrane transport sodium ion transmembrane transport inorganic ion transmembrane transport establishment of localization metal ion transport inorganic cation transmembrane transport transmembrane transport monoatomic cation transmembrane transport localization monoatomic ion transport monoatomic cation transport sodium ion transport nervous system process transmission of nerve impulse cell communication neuronal action potential detection of external stimulus detection of stimulus involved in sensory perception of pain response to external stimulus sensory perception of temperature stimulus sensory perception of pain detection of temperature stimulus involved in sensory perception response to temperature stimulus detection of abiotic stimulus detection of stimulus sensory perception detection of temperature stimulus response to abiotic stimulus detection of stimulus involved in sensory perception detection of temperature stimulus involved in sensory perception of pain action potential propagation defense response inflammatory response developmental process multicellular organism development anatomical structure development post-embryonic development response to mechanical stimulus detection of mechanical stimulus involved in sensory perception sensory perception of mechanical stimulus detection of mechanical stimulus	protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane plasma membrane membrane protein complex cation channel complex transporter complex cell periphery cellular anatomical structure transmembrane transporter complex monoatomic ion channel complex axon protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane plasma membrane membrane protein complex cation channel complex transporter complex cell periphery cellular anatomical structure transmembrane transporter complex monoatomic ion channel complex axon cell projection main axon neuron projection node of Ranvier plasma membrane bounded cell projection synapse axon terminus presynapse distal axon cell junction neuron projection terminus
D [auth E], E [auth F], F [auth G], G [auth H]	Beta/omega-theraphotoxin-Tp2a	channel regulator activity ion channel regulator activity molecular function regulator activity sodium channel regulator activity transporter regulator activity binding lipid binding calcium channel regulator activity toxin activity	-	cellular anatomical structure extracellular region
H [auth I], J [auth K]	Fab light chain	-	-	-
I [auth J], K [auth L]	Fab heavy chain	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth B], B [auth C], C [auth D], L [auth A]	IPR005821	Ion transport domain	Domain
A [auth B], B [auth C], C [auth D], L [auth A]	IPR043203	Voltage-gated cation channel calcium and sodium	Family
A [auth B], B [auth C], C [auth D], L [auth A]	IPR027359	Voltage-dependent channel domain superfamily	Homologous Superfamily
A [auth B], B [auth C], C [auth D], L [auth A]	IPR024583	Voltage-gated Na+ ion channel, cytoplasmic domain	Domain
A [auth B], B [auth C], C [auth D], L [auth A]	IPR001696	Voltage gated sodium channel, alpha subunit	Family
A [auth B], B [auth C], C [auth D], L [auth A]	IPR000048	IQ motif, EF-hand binding site	Binding Site
A [auth B], B [auth C], C [auth D], L [auth A]	IPR010526	Sodium ion transport-associated domain	Domain
A [auth B], B [auth C], C [auth D], L [auth A]	IPR005821	Ion transport domain	Domain
A [auth B], B [auth C], C [auth D], L [auth A]	IPR044564	Voltage-gated sodium channel alpha subunit, inactivation gate	Domain
A [auth B], B [auth C], C [auth D], L [auth A]	IPR043203	Voltage-gated cation channel calcium and sodium	Family
A [auth B], B [auth C], C [auth D], L [auth A]	IPR027359	Voltage-dependent channel domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth B], B [auth C], C [auth D], L [auth A]	Pharos: Q15858	paroxysmal extreme pain disorder erythromelalgia epilepsy channelopathy-associated congenital insensitivity to pain, autosomal recessive generalized epilepsy with febrile seizures plus primary erythermalgia neuralgia partial epilepsy Pruritus hereditary sensory and autonomic neuropathy type 2 peripheral neuropathy postherpetic neuralgia generalized epilepsy with febrile seizures plus, type 7 early myoclonic encephalopathy neuropathy, hereditary sensory and autonomic, type 2A paroxysmal extreme pain disorder erythromelalgia epilepsy channelopathy-associated congenital insensitivity to pain, autosomal recessive generalized epilepsy with febrile seizures plus primary erythermalgia neuralgia partial epilepsy Pruritus hereditary sensory and autonomic neuropathy type 2 peripheral neuropathy postherpetic neuralgia generalized epilepsy with febrile seizures plus, type 7 early myoclonic encephalopathy neuropathy, hereditary sensory and autonomic, type 2A tinea pedis lung cancer urethritis malignant ependymoma peripheral nervous system disease pituitary cancer generalized epilepsy with febrile seizures plus, type 2 hemorrhoid Lennox-Gastaut syndrome status epilepticus developmental and epileptic encephalopathy, 6 tinea corporis malignant mesothelioma Morvan syndrome Herpesviridae infectious disease bipolar disorder Riley-Day syndrome intellectual disability Charcot-Marie-Tooth disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Dravet syndrome trigeminal neuralgia malignant colon neoplasm Pediculus humanus capitis infestation epilepsy with generalized tonic-clonic seizures pilocytic astrocytoma familial infantile myoclonic epilepsy premature ejaculation glossopharyngeal neuralgia hereditary sensory and autonomic neuropathy Pthirus pubis infestation scabies osteosarcoma cystic fibrosis

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A [auth B], B [auth C], C [auth D], L [auth A]	OPM	Transmembrane	Alpha-helical polytopic	Ion channel (VIC) superfamily	Voltage-gated calcium and sodium channels

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Chains	External Link	Comment
A [auth B], B [auth C], C [auth D], L [auth A]	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: MemProtMD MemProtMD Database Homepage

Chains	External Link	Comment
A [auth B], B [auth C], C [auth D], L [auth A]	MemProtMD	Annotated as membrane protein by MemProtMD

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A [auth B], B [auth C], C [auth D], L [auth A]	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	Channels: Potassium, Sodium, & Proton Ion-Selective	Na_V1.7 sodium channel voltage-sensor domain with bound ProTx2

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.