3OTF

Structural basis for the cAMP-dependent gating in human HCN4 channel

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3otfa_	All beta proteins	Double-stranded beta-helix	cAMP-binding domain-like	cAMP-binding domain	automated matches	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	SCOP2B Superfamily	cAMP-binding domain-like	8067908	3000084	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	cNMP_binding_1	e3otfA1	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: cNMP_binding_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.287.630	Mainly Alpha	Orthogonal Bundle	Helix Hairpins	Helix hairpin bin	CATH (4.3.0)
A	2.60.120.10	Mainly Beta	Sandwich	Jelly Rolls	Jelly Rolls	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00027	Cyclic nucleotide-binding domain (cNMP_binding)	Cyclic nucleotide-binding domain	This domain sensor domain can bind cAMP, cGMP, c-di-GMP, oxygen and 2-oxoglutarate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4	monoatomic cation transmembrane transporter activity gated channel activity 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 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 monoatomic cation transmembrane transporter activity gated channel activity 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 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 voltage-gated sodium channel activity sodium channel activity sodium ion transmembrane transporter activity binding adenyl ribonucleotide binding cyclic nucleotide binding nucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding cAMP binding adenyl nucleotide binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding voltage-gated potassium channel activity involved in SA node cell action potential depolarization intracellularly ligand-gated monoatomic ion channel activity intracellularly cyclic nucleotide-activated monoatomic cation channel activity ligand-gated channel activity ligand-gated monoatomic ion channel activity intracellularly cAMP-activated cation channel activity ligand-gated monoatomic cation channel activity cyclic nucleotide-activated monoatomic ion channel activity identical protein binding protein 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 multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process 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 multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation regulation of heart rate transport monoatomic ion transmembrane transport potassium 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 potassium ion transport cellular process monoatomic cation transport SA node cell to atrial cardiac muscle cell signaling signaling cell-cell signaling involved in cardiac conduction SA node cell to atrial cardiac muscle cell communication cell communication cell communication involved in cardiac conduction SA node cell action potential cell-cell signaling cardiac conduction membrane depolarization during SA node cell action potential regulation of cellular process regulation of membrane depolarization cellular response to nitrogen compound cellular response to stimulus response to stimulus response to organophosphorus cellular response to organic cyclic compound response to oxygen-containing compound response to nitrogen compound response to purine-containing compound response to cAMP cellular response to oxygen-containing compound cellular response to chemical stimulus response to chemical cellular response to cAMP response to organic cyclic compound regulation of cardiac muscle contraction cardiac muscle contraction muscle contraction muscle system process regulation of muscle system process striated muscle contraction regulation of striated muscle contraction regulation of muscle contraction sodium ion transmembrane transport sodium ion transport import into cell import across plasma membrane sodium ion import across plasma membrane inorganic cation import across plasma membrane inorganic ion import across plasma membrane regulation of actin filament-based process regulation of cardiac muscle cell action potential actin filament-based process cardiac muscle cell contraction regulation of action potential actin filament-based movement regulation of cardiac muscle cell action potential involved in regulation of contraction regulation of actin filament-based movement regulation of cardiac muscle cell contraction actin-mediated cell contraction developmental process heart development cardiac conduction system development cardiac muscle tissue development animal organ development tissue development atrial cardiac muscle tissue development striated muscle tissue development circulatory system development multicellular organism development anatomical structure development sinoatrial node development muscle tissue development system development potassium ion import across plasma membrane cellular response to cGMP response to cGMP regulation of heart rate by cardiac conduction	cell periphery plasma membrane membrane cellular anatomical entity somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection intracellular anatomical structure perinuclear region of cytoplasm cytoplasm voltage-gated potassium channel complex cell periphery plasma membrane membrane cellular anatomical entity somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection intracellular anatomical structure perinuclear region of cytoplasm cytoplasm voltage-gated potassium channel complex protein-containing complex plasma membrane protein complex HCN channel complex potassium channel complex membrane protein complex cation channel complex transporter complex transmembrane transporter complex monoatomic ion channel complex axon

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR013621	Ion transport N-terminal	Domain
A	IPR014710	RmlC-like jelly roll fold	Homologous Superfamily
A	IPR018488	Cyclic nucleotide-binding, conserved site	Conserved Site
A	IPR005821	Ion transport domain	Domain
A	IPR051413	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel	Family
A	IPR003938	Potassium channel, voltage-dependent, EAG/ELK/ERG-like	Family
A	IPR000595	Cyclic nucleotide-binding domain	Domain
A	IPR018490	Cyclic nucleotide-binding domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q9Y3Q4	atrial fibrillation Brugada syndrome sick sinus syndrome 2, autosomal dominant Brugada syndrome 8 sick sinus syndrome Paroxysmal atrial fibrillation epilepsy left ventricular noncompaction familial atrial fibrillation lung carcinoma osteosarcoma psoriasis Stevens-Johnson syndrome heart disease Marfan syndrome atrial fibrillation Brugada syndrome sick sinus syndrome 2, autosomal dominant Brugada syndrome 8 sick sinus syndrome Paroxysmal atrial fibrillation epilepsy left ventricular noncompaction familial atrial fibrillation lung carcinoma osteosarcoma psoriasis Stevens-Johnson syndrome heart disease Marfan syndrome thoracic aortic aneurysm

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.