1XMU

Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Roflumilast

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)
B	d1xmub_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1xmua_	All alpha proteins	HD-domain/PDEase-like	HD-domain/PDEase-like	PDEase	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	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)
B	SCOP2B Superfamily	HD-domain/PDEase-like	8038771	3000943	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	HD-domain/PDEase-like	8038771	3000943	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	PDEase_I	e1xmuB1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: PDEase_I	ECOD (1.6)
A	PDEase_I	e1xmuA1	A: alpha complex topology	X: PDEase-like	H: HD-domain/PDEase-like (From Topology)	T: HD-domain/PDEase-like	F: PDEase_I	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	1.10.1300.10	Mainly Alpha	Orthogonal Bundle	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	CATH (4.3.0)
A	1.10.1300.10	Mainly Alpha	Orthogonal Bundle	Catalytic domain of cyclic nucleotide phosphodiesterase 4b2b	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B	PF00233	3'5'-cyclic nucleotide phosphodiesterase (PDEase_I)	3'5'-cyclic nucleotide phosphodiesterase	-	Domain
A	PF00233	3'5'-cyclic nucleotide phosphodiesterase (PDEase_I)	3'5'-cyclic nucleotide phosphodiesterase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity 3',5'-cyclic-AMP phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity cytoskeletal protein binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity 3',5'-cyclic-AMP phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity cytoskeletal protein binding protein binding binding gamma-tubulin binding tubulin binding transmembrane transporter 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 3',5'-cyclic-GMP phosphodiesterase activity cation binding metal ion binding	heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction regulation of biological process biological regulation regulation of cardiac muscle contraction actin filament-based movement muscle contraction muscle system process regulation of muscle system process regulation of blood circulation regulation of striated muscle contraction regulation of actin filament-based movement regulation of muscle contraction regulation of cardiac muscle cell contraction cellular process actin-mediated cell contraction heart contraction cellular response to stimulus immune response-regulating cell surface receptor signaling pathway response to stimulus signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of response to stimulus immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response negative regulation of signaling negative regulation of biological process regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway negative regulation of cell communication negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway adrenergic receptor signaling pathway negative regulation of cellular process regulation of G protein-coupled receptor signaling pathway adenylate cyclase-activating adrenergic receptor signaling pathway regulation of signaling negative regulation of response to stimulus adenylate cyclase-activating G protein-coupled receptor signaling pathway negative regulation of signal transduction negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway regulation of cell communication G protein-coupled receptor signaling pathway regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway cell chemotaxis chemotaxis neutrophil chemotaxis response to external stimulus neutrophil migration granulocyte migration leukocyte migration cellular response to chemical stimulus taxis granulocyte chemotaxis response to chemical myeloid leukocyte migration cell migration cell motility leukocyte chemotaxis locomotion biological process involved in interspecies interaction between organisms response to lipid response to other organism cellular response to lipopolysaccharide response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound response to biotic stimulus cellular response to biotic stimulus response to bacterium cellular response to lipid response to external biotic stimulus response to molecule of bacterial origin response to epinephrine cellular response to epinephrine stimulus positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of interleukin-2 production interleukin-2 production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of interleukin-2 production regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process multicellular organismal-level homeostasis leukocyte homeostasis homeostatic process homeostasis of number of cells myeloid cell homeostasis neutrophil homeostasis cellular response to xenobiotic stimulus response to xenobiotic stimulus intracellular signal transduction cAMP-mediated signaling intracellular signaling cassette regulation of calcium ion transport regulation of localization transport monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport calcium ion transport metal ion transport regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport localization regulation of calcium ion transmembrane transport via high voltage-gated calcium channel monoatomic ion transport calcium ion transmembrane transport via high voltage-gated calcium channel monoatomic cation transport regulation of metal ion transport regulation of transport regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport regulation of transmembrane transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport negative regulation of relaxation of muscle relaxation of cardiac muscle regulation of relaxation of cardiac muscle relaxation of muscle negative regulation of relaxation of cardiac muscle regulation of relaxation of muscle negative regulation of multicellular organismal process ribose phosphate metabolic process ribonucleotide catabolic process catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process cyclic nucleotide metabolic process nucleobase-containing compound metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process phosphorus metabolic process nucleotide catabolic process nucleoside phosphate metabolic process cAMP catabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process cAMP metabolic process cyclic purine nucleotide metabolic process primary metabolic process purine-containing compound catabolic process cyclic nucleotide catabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound catabolic process organophosphate metabolic process purine ribonucleotide metabolic process regulation of type II interferon production type II interferon production positive regulation of type II interferon production	intracellular anatomical structure intracellular membraneless organelle Z disc sarcomere intracellular organelle I band cellular anatomical structure organelle membraneless organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer intracellular anatomical structure intracellular membraneless organelle Z disc sarcomere intracellular organelle I band cellular anatomical structure organelle membraneless organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex centrosome microtubule organizing center cytoskeleton microtubule cytoskeleton cytosol protein-containing complex gamma-tubulin complex neuron spine synapse neuron projection dendritic spine plasma membrane bounded cell projection somatodendritic compartment cell projection postsynapse cell junction dendrite dendritic tree excitatory synapse postsynaptic density neuron to neuron synapse postsynaptic specialization asymmetric synapse perinuclear region of cytoplasm plasma membrane protein complex voltage-gated calcium channel complex membrane plasma membrane membrane protein complex cation channel complex transporter complex cell periphery transmembrane transporter complex calcium channel complex monoatomic ion channel complex membrane-bounded organelle transport vesicle intracellular vesicle intracellular membrane-bounded organelle endomembrane system presynapse cytoplasmic vesicle synaptic vesicle secretory vesicle vesicle exocytic vesicle nucleus
A	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity 3',5'-cyclic-AMP phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity cytoskeletal protein binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity 3',5'-cyclic-nucleotide phosphodiesterase activity 3',5'-cyclic-AMP phosphodiesterase activity hydrolase activity cyclic-nucleotide phosphodiesterase activity catalytic activity channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity cytoskeletal protein binding protein binding binding gamma-tubulin binding tubulin binding transmembrane transporter 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 3',5'-cyclic-GMP phosphodiesterase activity cation binding metal ion binding	heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction heart process multicellular organismal process system process regulation of actin filament-based process regulation of cellular process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction circulatory system process actin filament-based process regulation of multicellular organismal process blood circulation cardiac muscle cell contraction regulation of biological process biological regulation regulation of cardiac muscle contraction actin filament-based movement muscle contraction muscle system process regulation of muscle system process regulation of blood circulation regulation of striated muscle contraction regulation of actin filament-based movement regulation of muscle contraction regulation of cardiac muscle cell contraction cellular process actin-mediated cell contraction heart contraction cellular response to stimulus immune response-regulating cell surface receptor signaling pathway response to stimulus signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of response to stimulus immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response negative regulation of signaling negative regulation of biological process regulation of signal transduction negative regulation of G protein-coupled receptor signaling pathway negative regulation of cell communication negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway adrenergic receptor signaling pathway negative regulation of cellular process regulation of G protein-coupled receptor signaling pathway adenylate cyclase-activating adrenergic receptor signaling pathway regulation of signaling negative regulation of response to stimulus adenylate cyclase-activating G protein-coupled receptor signaling pathway negative regulation of signal transduction negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway regulation of cell communication G protein-coupled receptor signaling pathway regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway cell chemotaxis chemotaxis neutrophil chemotaxis response to external stimulus neutrophil migration granulocyte migration leukocyte migration cellular response to chemical stimulus taxis granulocyte chemotaxis response to chemical myeloid leukocyte migration cell migration cell motility leukocyte chemotaxis locomotion biological process involved in interspecies interaction between organisms response to lipid response to other organism cellular response to lipopolysaccharide response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound response to biotic stimulus cellular response to biotic stimulus response to bacterium cellular response to lipid response to external biotic stimulus response to molecule of bacterial origin response to epinephrine cellular response to epinephrine stimulus positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process regulation of cytokine production cytokine production positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of interleukin-2 production interleukin-2 production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of interleukin-2 production regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process positive regulation of cytokine production regulation of metabolic process multicellular organismal-level homeostasis leukocyte homeostasis homeostatic process homeostasis of number of cells myeloid cell homeostasis neutrophil homeostasis cellular response to xenobiotic stimulus response to xenobiotic stimulus intracellular signal transduction cAMP-mediated signaling intracellular signaling cassette regulation of calcium ion transport regulation of localization transport monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport calcium ion transport metal ion transport regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport localization regulation of calcium ion transmembrane transport via high voltage-gated calcium channel monoatomic ion transport calcium ion transmembrane transport via high voltage-gated calcium channel monoatomic cation transport regulation of metal ion transport regulation of transport regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport regulation of transmembrane transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport negative regulation of relaxation of muscle relaxation of cardiac muscle regulation of relaxation of cardiac muscle relaxation of muscle negative regulation of relaxation of cardiac muscle regulation of relaxation of muscle negative regulation of multicellular organismal process ribose phosphate metabolic process ribonucleotide catabolic process catabolic process carbohydrate derivative metabolic process organophosphate catabolic process nucleoside phosphate catabolic process cyclic nucleotide metabolic process nucleobase-containing compound metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process phosphorus metabolic process nucleotide catabolic process nucleoside phosphate metabolic process cAMP catabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process cAMP metabolic process cyclic purine nucleotide metabolic process primary metabolic process purine-containing compound catabolic process cyclic nucleotide catabolic process nucleotide metabolic process purine-containing compound metabolic process nucleobase-containing compound catabolic process organophosphate metabolic process purine ribonucleotide metabolic process regulation of type II interferon production type II interferon production positive regulation of type II interferon production	intracellular anatomical structure intracellular membraneless organelle Z disc sarcomere intracellular organelle I band cellular anatomical structure organelle membraneless organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer intracellular anatomical structure intracellular membraneless organelle Z disc sarcomere intracellular organelle I band cellular anatomical structure organelle membraneless organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex centrosome microtubule organizing center cytoskeleton microtubule cytoskeleton cytosol protein-containing complex gamma-tubulin complex neuron spine synapse neuron projection dendritic spine plasma membrane bounded cell projection somatodendritic compartment cell projection postsynapse cell junction dendrite dendritic tree excitatory synapse postsynaptic density neuron to neuron synapse postsynaptic specialization asymmetric synapse perinuclear region of cytoplasm plasma membrane protein complex voltage-gated calcium channel complex membrane plasma membrane membrane protein complex cation channel complex transporter complex cell periphery transmembrane transporter complex calcium channel complex monoatomic ion channel complex membrane-bounded organelle transport vesicle intracellular vesicle intracellular membrane-bounded organelle endomembrane system presynapse cytoplasmic vesicle synaptic vesicle secretory vesicle vesicle exocytic vesicle nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B	IPR036971	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily	Homologous Superfamily
B	IPR023174	3'5'-cyclic nucleotide phosphodiesterase, conserved site	Conserved Site
B	IPR003607	HD/PDEase domain	Domain
B	IPR002073	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	Domain
B	IPR040844	Phosphodiesterase 4 upstream conserved regions (UCR)	Domain
B	IPR023088	3'5'-cyclic nucleotide phosphodiesterase	Family
A	IPR036971	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily	Homologous Superfamily
A	IPR023174	3'5'-cyclic nucleotide phosphodiesterase, conserved site	Conserved Site
A	IPR003607	HD/PDEase domain	Domain
A	IPR002073	3'5'-cyclic nucleotide phosphodiesterase, catalytic domain	Domain
A	IPR040844	Phosphodiesterase 4 upstream conserved regions (UCR)	Domain
A	IPR023088	3'5'-cyclic nucleotide phosphodiesterase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: Q07343	acute myeloid leukemia asthma bipolar disorder alcohol abuse amphetamine abuse schizophrenia Arsenic Poisoning atopic eczema lymphoplasmacytic lymphoma autism breast cancer myopathy chronic obstructive pulmonary disease oligodendroglioma Crohn disease acute myeloid leukemia asthma bipolar disorder alcohol abuse amphetamine abuse schizophrenia Arsenic Poisoning atopic eczema lymphoplasmacytic lymphoma autism breast cancer myopathy chronic obstructive pulmonary disease oligodendroglioma Crohn disease peripheral vascular disease adenoma depressive disorder psoriasis Down syndrome gastric carcinoma subependymal giant cell astrocytoma glioblastoma ulcerative colitis interstitial cystitis lung adenocarcinoma malignant ependymoma attention deficit hyperactivity disorder, inattentive type mood disorder bronchitis osteosarcoma cystic fibrosis pilocytic astrocytoma pulmonary emphysema sinusitis anxiety disorder gastroesophageal reflux disease head and neck cancer invasive ductal breast carcinoma lung cancer malignant mesothelioma atypical teratoid rhabdoid tumor medulloblastoma myocardial ischemia coronary artery disease ovarian cancer pituitary cancer dermatomyositis gastric cancer skin disease aphthous stomatitis Gaucher disease tuberculosis large cell medulloblastoma
A	Pharos: Q07343	acute myeloid leukemia asthma bipolar disorder alcohol abuse amphetamine abuse schizophrenia Arsenic Poisoning atopic eczema lymphoplasmacytic lymphoma autism breast cancer myopathy chronic obstructive pulmonary disease oligodendroglioma Crohn disease acute myeloid leukemia asthma bipolar disorder alcohol abuse amphetamine abuse schizophrenia Arsenic Poisoning atopic eczema lymphoplasmacytic lymphoma autism breast cancer myopathy chronic obstructive pulmonary disease oligodendroglioma Crohn disease peripheral vascular disease adenoma depressive disorder psoriasis Down syndrome gastric carcinoma subependymal giant cell astrocytoma glioblastoma ulcerative colitis interstitial cystitis lung adenocarcinoma malignant ependymoma attention deficit hyperactivity disorder, inattentive type mood disorder bronchitis osteosarcoma cystic fibrosis pilocytic astrocytoma pulmonary emphysema sinusitis anxiety disorder gastroesophageal reflux disease head and neck cancer invasive ductal breast carcinoma lung cancer malignant mesothelioma atypical teratoid rhabdoid tumor medulloblastoma myocardial ischemia coronary artery disease ovarian cancer pituitary cancer dermatomyositis gastric cancer skin disease aphthous stomatitis Gaucher disease tuberculosis large cell medulloblastoma

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.