6J8I

Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, ProTx-II and tetrodotoxin (Y1755 up)

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
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: mpstruc

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A [auth C]	PF07686	e6j8iC1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
B [auth A]	PF00520	e6j8iA2	A: alpha complex topology	X: Voltage-gated ion channels (From Topology)	H: Voltage-gated ion channels (From Topology)	T: Voltage-gated ion channels	F: PF00520	ECOD (1.6)
C [auth B]	PF07686	e6j8iB1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: PF07686	ECOD (1.6)
C [auth B]	F_UNCLASSIFIED	e6j8iB2	A: extended segments	X: Fibroblast growth factor receptor 3 transmembrane domain (From Topology)	H: Fibroblast growth factor receptor 3 transmembrane domain (From Topology)	T: Fibroblast growth factor receptor 3 transmembrane domain	F: F_UNCLASSIFIED	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth C]	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth C]	PF07686	Immunoglobulin V-set domain (V-set)	Immunoglobulin V-set domain	This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.	Domain
B [auth A]	PF00520	Ion transport protein (Ion_trans)	Ion transport protein	-	Family
C [auth B]	PF07686	Immunoglobulin V-set domain (V-set)	Immunoglobulin V-set domain	This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth C]	Sodium channel subunit beta-2	monoatomic cation transmembrane transporter activity gated channel activity voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization monoatomic ion channel activity potassium ion transmembrane transporter activity voltage-gated channel activity voltage-gated monoatomic ion channel activity potassium channel activity voltage-gated monoatomic cation channel activity voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization monoatomic cation channel activity passive transmembrane transporter activity voltage-gated potassium channel activity inorganic molecular entity transmembrane transporter activity channel activity monoatomic cation transmembrane transporter activity gated channel activity voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization monoatomic ion channel activity potassium ion transmembrane transporter activity voltage-gated channel activity voltage-gated monoatomic ion channel activity potassium channel activity voltage-gated monoatomic cation channel activity voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization monoatomic cation channel activity passive transmembrane transporter activity voltage-gated potassium channel 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 channel regulator activity ion channel regulator activity molecular function regulator activity sodium channel regulator activity transporter regulator activity voltage-gated sodium channel activity involved in cardiac muscle cell action potential voltage-gated sodium channel activity sodium channel activity sodium ion transmembrane transporter activity	membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction actin filament-based movement membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction actin filament-based movement cardiac muscle contraction muscle contraction muscle system process striated muscle contraction circulatory system process actin filament-based process cellular process actin-mediated cell contraction heart contraction blood circulation regulation of localization regulation of cellular process transport monoatomic ion transmembrane transport regulation of transmembrane transporter activity sodium ion transmembrane transport regulation of monoatomic ion transmembrane transport regulation of sodium ion transport regulation of sodium ion transmembrane transport metal ion transport regulation of transporter activity monoatomic cation transmembrane transport regulation of sodium ion transmembrane transporter activity localization monoatomic ion transport monoatomic cation transport regulation of metal ion transport regulation of monoatomic ion transmembrane transporter activity regulation of biological process regulation of transport regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport regulation of molecular function regulation of transmembrane transport regulation of monoatomic cation transmembrane transport sodium ion transport regulation of membrane depolarization regulation of atrial cardiac muscle cell membrane depolarization organic substance metabolic process biosynthetic process cellular biosynthetic process cellular metabolic process organic substance biosynthetic process metabolic process macromolecule metabolic process gene expression macromolecule biosynthetic process developmental process multicellular organism development anatomical structure development nervous system development system development trans-synaptic signaling synaptic signaling signaling anterograde trans-synaptic signaling cell-cell signaling chemical synaptic transmission cell communication response to stimulus response to stress response to heat response to abiotic stimulus response to temperature stimulus response to chemical response to pyrethroid response to insecticide response to toxic substance regulation of heart contraction regulation of system process regulation of blood circulation cardiac conduction regulation of multicellular organismal process regulation of heart rate by cardiac conduction regulation of heart rate	cell periphery sarcolemma plasma membrane membrane T-tubule cellular anatomical entity protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex cell periphery sarcolemma plasma membrane membrane T-tubule cellular anatomical entity protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex monoatomic ion channel complex synapse cell junction
B [auth A]	Sodium channel protein type 9 subunit alpha	calcium channel activity monoatomic cation transmembrane transporter activity voltage-gated calcium channel activity gated channel activity monoatomic ion channel activity voltage-gated channel activity voltage-gated monoatomic ion channel activity voltage-gated monoatomic cation channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity calcium channel activity monoatomic cation transmembrane transporter activity voltage-gated calcium channel activity gated channel activity monoatomic ion channel activity voltage-gated channel activity voltage-gated monoatomic ion channel activity voltage-gated monoatomic cation channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity high voltage-gated calcium channel activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity voltage-gated sodium channel activity sodium channel activity sodium ion transmembrane transporter activity	rhythmic process circadian rhythm response to stimulus response to chemical response to toxic substance behavior multicellular organismal process response to stress multicellular organismal response to stress response to pain behavioral response to pain transport monoatomic ion transmembrane transport sodium ion transmembrane transport rhythmic process circadian rhythm response to stimulus response to chemical response to toxic substance behavior multicellular organismal process 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 cellular process monoatomic cation transport sodium ion transport import into cell calcium ion transmembrane import into cytosol import across plasma membrane inorganic cation import across plasma membrane calcium ion transport calcium ion import across plasma membrane inorganic ion import across plasma membrane calcium ion import calcium ion import into cytosol calcium ion transmembrane transport detection of external stimulus system process detection of stimulus involved in sensory perception of pain nervous system process 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 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	cell periphery plasma membrane membrane cellular anatomical entity protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex monoatomic ion channel complex axon cell periphery plasma membrane membrane cellular anatomical entity protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex monoatomic ion channel complex axon cell projection neuron projection plasma membrane bounded cell projection voltage-gated calcium channel complex calcium channel complex
C [auth B]	Sodium channel subunit beta-1	molecular function inhibitor activity sodium channel inhibitor activity channel regulator activity transporter inhibitor activity ion channel regulator activity ion channel inhibitor activity molecular function regulator activity sodium channel regulator activity transporter regulator activity channel inhibitor activity monoatomic cation transmembrane transporter activity voltage-gated sodium channel activity involved in cardiac muscle cell action potential voltage-gated sodium channel activity monoatomic ion channel activity molecular function inhibitor activity sodium channel inhibitor activity channel regulator activity transporter inhibitor activity ion channel regulator activity ion channel inhibitor activity molecular function regulator activity sodium channel regulator activity transporter regulator activity channel inhibitor activity monoatomic cation transmembrane transporter activity voltage-gated sodium channel activity involved in cardiac muscle cell action potential voltage-gated sodium channel activity monoatomic ion channel activity sodium channel activity voltage-gated sodium channel activity involved in Purkinje myocyte action potential 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 protein binding binding transmembrane transporter binding	membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction actin filament-based movement membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process cardiac muscle cell contraction multicellular organismal process system process cardiac muscle cell action potential involved in contraction actin filament-based movement cardiac muscle contraction muscle contraction muscle system process striated muscle contraction circulatory system process actin filament-based process cellular process actin-mediated cell contraction heart contraction blood circulation regulation of localization regulation of cellular process transport monoatomic ion transmembrane transport regulation of transmembrane transporter activity sodium ion transmembrane transport regulation of monoatomic ion transmembrane transport regulation of sodium ion transport regulation of sodium ion transmembrane transport metal ion transport regulation of transporter activity monoatomic cation transmembrane transport regulation of sodium ion transmembrane transporter activity localization monoatomic ion transport monoatomic cation transport regulation of metal ion transport regulation of monoatomic ion transmembrane transporter activity regulation of biological process regulation of transport regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport regulation of molecular function regulation of transmembrane transport regulation of monoatomic cation transmembrane transport sodium ion transport regulation of membrane depolarization regulation of atrial cardiac muscle cell membrane depolarization cardiac muscle cell membrane repolarization membrane repolarization regulation of membrane repolarization ventricular cardiac muscle cell membrane repolarization regulation of cardiac muscle cell membrane repolarization regulation of ventricular cardiac muscle cell membrane repolarization axonogenesis cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development central nervous system neuron development neuron projection development cell morphogenesis cellular component organization neurogenesis multicellular organism development central nervous system neuron differentiation cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation anatomical structure development cellular component organization or biogenesis corticospinal neuron axon guidance system development developmental process central nervous system projection neuron axonogenesis central nervous system neuron axonogenesis plasma membrane bounded cell projection organization axon guidance nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons anatomical structure morphogenesis central nervous system development neuron projection guidance neuron development corticospinal tract morphogenesis regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization positive regulation of biological process positive regulation of neuron projection development positive regulation of cell projection organization positive regulation of cellular process regulation of cell projection organization regulation of plasma membrane bounded cell projection organization locomotion positive regulation of cation transmembrane transport positive regulation of sodium ion transport positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport regulation of voltage-gated sodium channel activity positive regulation of cation channel activity regulation of cation channel activity positive regulation of voltage-gated sodium channel activity positive regulation of sodium ion transmembrane transporter activity positive regulation of molecular function positive regulation of transmembrane transport positive regulation of sodium ion transmembrane transport positive regulation of transport positive regulation of transporter activity positive regulation of ion transmembrane transporter activity regulation of heart contraction regulation of system process regulation of blood circulation cardiac conduction regulation of multicellular organismal process cell adhesion Purkinje myocyte to ventricular cardiac muscle cell communication membrane depolarization during Purkinje myocyte cell action potential signaling cell-cell signaling involved in cardiac conduction cell communication Purkinje myocyte action potential cell communication involved in cardiac conduction cell-cell signaling Purkinje myocyte to ventricular cardiac muscle cell signaling nervous system process action potential propagation transmission of nerve impulse neuronal action potential propagation regulation of heart rate by cardiac conduction regulation of heart rate	cell periphery sarcolemma plasma membrane membrane T-tubule cellular anatomical entity somatodendritic compartment cell body perikaryon neuronal cell body axon cell projection main axon neuron projection cell periphery sarcolemma plasma membrane membrane T-tubule cellular anatomical entity somatodendritic compartment cell body perikaryon neuronal cell body axon cell projection main axon neuron projection node of Ranvier plasma membrane bounded cell projection extracellular region protein-containing complex sodium channel complex voltage-gated sodium channel complex plasma membrane protein complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex monoatomic ion channel complex cell-cell junction intercalated disc anchoring junction cell junction cell-cell contact zone

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth C]	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A [auth C]	IPR003599	Immunoglobulin subtype	Domain
A [auth C]	IPR000920	Myelin P0 protein-related	Family
A [auth C]	IPR013106	Immunoglobulin V-set domain	Domain
A [auth C]	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A [auth C]	IPR007110	Immunoglobulin-like domain	Domain
B [auth A]	IPR024583	Voltage-gated Na+ ion channel, cytoplasmic domain	Domain
B [auth A]	IPR001696	Voltage gated sodium channel, alpha subunit	Family
B [auth A]	IPR000048	IQ motif, EF-hand binding site	Binding Site
B [auth A]	IPR010526	Sodium ion transport-associated domain	Domain
B [auth A]	IPR005821	Ion transport domain	Domain
B [auth A]	IPR044564	Voltage-gated sodium channel alpha subunit, inactivation gate	Domain
B [auth A]	IPR043203	Voltage-gated cation channel calcium and sodium	Family
B [auth A]	IPR027359	Voltage-dependent channel domain superfamily	Homologous Superfamily
C [auth B]	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
C [auth B]	IPR013106	Immunoglobulin V-set domain	Domain
C [auth B]	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
C [auth B]	IPR027098	Sodium channel subunit beta-1/beta-3	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth C]	Pharos: O60939	Brugada syndrome familial atrial fibrillation atrial fibrillation, familial, 14 lung adenocarcinoma pituitary cancer astrocytic tumor glioblastoma lung carcinoma medulloblastoma Pick disease primitive neuroectodermal tumor atrial fibrillation atypical teratoid rhabdoid tumor Epileptic encephalopathy large cell medulloblastoma Brugada syndrome familial atrial fibrillation atrial fibrillation, familial, 14 lung adenocarcinoma pituitary cancer astrocytic tumor glioblastoma lung carcinoma medulloblastoma Pick disease primitive neuroectodermal tumor atrial fibrillation atypical teratoid rhabdoid tumor Epileptic encephalopathy large cell medulloblastoma malignant ependymoma non-small cell lung carcinoma pilocytic astrocytoma subependymal giant cell astrocytoma atrial fibrillation, familial, 1 breast cancer malignant glioma oligodendroglioma
B [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 peripheral nervous system disease urethritis malignant ependymoma pituitary cancer generalized epilepsy with febrile seizures plus, type 2 hemorrhoid Lennox-Gastaut syndrome developmental and epileptic encephalopathy, 6 status epilepticus tinea corporis malignant mesothelioma Morvan syndrome Riley-Day syndrome Herpesviridae infectious disease bipolar disorder Charcot-Marie-Tooth disease intellectual disability Dravet syndrome pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia epilepsy with generalized tonic-clonic seizures trigeminal neuralgia malignant colon neoplasm Pediculus humanus capitis infestation pilocytic astrocytoma familial infantile myoclonic epilepsy premature ejaculation glossopharyngeal neuralgia Pthirus pubis infestation hereditary sensory and autonomic neuropathy scabies cystic fibrosis osteosarcoma
C [auth B]	Pharos: Q07699	Brugada syndrome Sudden infant death syndrome Brugada syndrome 5 familial atrial fibrillation generalized epilepsy with febrile seizures plus, type 1 atrial fibrillation, familial, 13 developmental and epileptic encephalopathy, 52 epilepsy generalized epilepsy with febrile seizures plus intellectual disability atrial fibrillation autosomal dominant cardiac arrhythmia (Kuhn) developmental and epileptic encephalopathy, 6 progressive familial heart block atrial fibrillation, familial, 1 Brugada syndrome Sudden infant death syndrome Brugada syndrome 5 familial atrial fibrillation generalized epilepsy with febrile seizures plus, type 1 atrial fibrillation, familial, 13 developmental and epileptic encephalopathy, 52 epilepsy generalized epilepsy with febrile seizures plus intellectual disability atrial fibrillation autosomal dominant cardiac arrhythmia (Kuhn) developmental and epileptic encephalopathy, 6 progressive familial heart block atrial fibrillation, familial, 1 dilated cardiomyopathy Hodgkins lymphoma progressive familial heart block, type 1A Dravet syndrome

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A [auth C], B [auth A], C [auth B]	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 C], B [auth A], C [auth B]	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A [auth C], B [auth A], C [auth B]	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	Channels: Potassium, Sodium, & Proton Ion-Selective	Na_V1.7 with β1β2 subunits in complex with huwentoxin-IV and saxitoxin (Y1755 up)

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.