4KU7

Structures of PKGI Reveal a cGMP-Selective Activation Mechanism

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	d4ku7a_	All beta proteins	Double-stranded beta-helix	cAMP-binding domain-like	automated matches	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	SCOP2 Family	cNMP-binding domain	8088269	4000272	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	cAMP-binding domain-like	8088270	3000084	SCOP2 (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	e4ku7A1	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	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	cGMP-dependent protein kinase 1	guanyl nucleotide binding binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding guanyl nucleotide binding binding cyclic nucleotide binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding cGMP binding small molecule binding channel regulator activity ion channel regulator activity calcium channel regulator activity molecular function regulator activity transporter regulator activity adenyl ribonucleotide binding purine ribonucleoside triphosphate binding adenyl nucleotide binding ATP binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups identical protein binding protein binding protein serine kinase activity kinase binding enzyme binding mitogen-activated protein kinase p38 binding protein kinase binding mitogen-activated protein kinase binding protein serine/threonine kinase activity cyclic nucleotide-dependent protein kinase activity cGMP-dependent protein kinase activity	multicellular organismal process system process regulation of system process negative regulation of biological process negative regulation of muscle contraction circulatory system process smooth muscle contraction regulation of smooth muscle contraction regulation of multicellular organismal process blood vessel diameter maintenance regulation of biological quality negative regulation of smooth muscle contraction blood circulation regulation of tube diameter multicellular organismal process system process regulation of system process negative regulation of biological process negative regulation of muscle contraction circulatory system process smooth muscle contraction regulation of smooth muscle contraction regulation of multicellular organismal process blood vessel diameter maintenance regulation of biological quality negative regulation of smooth muscle contraction blood circulation regulation of tube diameter regulation of biological process relaxation of smooth muscle regulation of tube size biological regulation muscle contraction muscle system process regulation of muscle system process relaxation of muscle relaxation of vascular associated smooth muscle regulation of muscle contraction vascular process in circulatory system negative regulation of multicellular organismal process vasodilation regulation of anatomical structure size regulation of body fluid levels regulation of cellular process response to stimulus regulation of cell activation negative regulation of cell adhesion negative regulation of platelet activation regulation of coagulation response to wounding negative regulation of homotypic cell-cell adhesion negative regulation of wound healing negative regulation of blood coagulation response to external stimulus blood coagulation negative regulation of hemostasis regulation of platelet activation regulation of response to stimulus negative regulation of response to external stimulus negative regulation of cell-cell adhesion regulation of wound healing platelet activation regulation of response to external stimulus homotypic cell-cell adhesion regulation of response to wounding cell adhesion cell-cell adhesion response to stress regulation of response to stress negative regulation of cellular process coagulation regulation of cell-cell adhesion regulation of hemostasis wound healing negative regulation of response to stimulus regulation of homotypic cell-cell adhesion regulation of cell adhesion regulation of blood coagulation hemostasis cell activation negative regulation of platelet aggregation negative regulation of response to wounding platelet aggregation negative regulation of cell activation regulation of platelet aggregation negative regulation of coagulation cellular process developmental process head development animal organ development brain development nervous system development multicellular organism development cerebellum development central nervous system development metencephalon development anatomical structure development hindbrain development system development cellular component organization organelle organization actin cytoskeleton organization actin filament-based process cellular component organization or biogenesis cytoskeleton organization spermatid development spermatid differentiation sexual reproduction cellular developmental process spermatogenesis reproductive process multicellular organismal reproductive process cell development cellular process involved in reproduction in multicellular organism developmental process involved in reproduction gamete generation male gamete generation cell differentiation germ cell development protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process cardiac muscle cell development developmental growth organ growth muscle cell differentiation cell growth striated muscle tissue development muscle structure development striated muscle cell development muscle cell development cardiac muscle hypertrophy cardiac cell development muscle tissue development cardiac muscle tissue growth muscle hypertrophy heart development heart growth developmental cell growth cardiac muscle tissue development physiological muscle hypertrophy growth cardiac muscle cell differentiation striated muscle hypertrophy tissue development cardiocyte differentiation circulatory system development cell growth involved in cardiac muscle cell development physiological cardiac muscle hypertrophy striated muscle cell differentiation regulation of molecular function regulation of catalytic activity regulation of hydrolase activity regulation of GTPase activity regulation of steroid biosynthetic process ketone metabolic process organic hydroxy compound metabolic process steroid metabolic process regulation of lipid metabolic process lipid biosynthetic process regulation of primary metabolic process regulation of small molecule metabolic process regulation of testosterone biosynthetic process small molecule metabolic process steroid biosynthetic process regulation of biosynthetic process small molecule biosynthetic process olefinic compound biosynthetic process regulation of ketone biosynthetic process regulation of steroid metabolic process regulation of ketone metabolic process testosterone biosynthetic process biosynthetic process organic hydroxy compound biosynthetic process olefinic compound metabolic process regulation of lipid biosynthetic process regulation of metabolic process ketone biosynthetic process lipid metabolic process regulation of vascular associated smooth muscle cell proliferation negative regulation of cell population proliferation cell population proliferation regulation of smooth muscle cell proliferation negative regulation of vascular associated smooth muscle cell proliferation smooth muscle cell proliferation negative regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation vascular associated smooth muscle cell proliferation positive regulation of cytosolic calcium ion concentration negative regulation of small molecule metabolic process regulation of inositol phosphate biosynthetic process negative regulation of phosphate metabolic process alcohol metabolic process inositol phosphate metabolic process regulation of phosphate metabolic process polyol biosynthetic process regulation of carbohydrate metabolic process negative regulation of carbohydrate metabolic process carbohydrate metabolic process polyol metabolic process regulation of alcohol biosynthetic process negative regulation of inositol phosphate biosynthetic process negative regulation of metabolic process carbohydrate biosynthetic process organophosphate metabolic process negative regulation of biosynthetic process organophosphate biosynthetic process inositol phosphate biosynthetic process alcohol biosynthetic process negative regulation of phosphorus metabolic process negative regulation of alcohol biosynthetic process regulation of phosphorus metabolic process regulation of carbohydrate biosynthetic process cellular response to stimulus signaling cGMP-mediated signaling intracellular signal transduction cell communication intracellular signaling cassette signal transduction regulation of vascular associated smooth muscle cell migration negative regulation of locomotion vascular associated smooth muscle cell migration regulation of cell motility negative regulation of vascular associated smooth muscle cell migration regulation of smooth muscle cell migration smooth muscle cell migration muscle cell migration negative regulation of smooth muscle cell migration regulation of locomotion regulation of cell migration negative regulation of cell motility cell migration cell motility locomotion negative regulation of cell migration protein kinase A signaling regulation of localization negative regulation of amino acid transport nitrogen compound transport negative regulation of amine transport transport regulation of glutamate secretion negative regulation of transport localization secretion by cell regulation of secretion by cell negative regulation of secretion negative regulation of glutamate secretion regulation of amino acid transport glutamate secretion negative regulation of secretion by cell organic anion transport carboxylic acid transport secretion regulation of transport export from cell establishment of localization regulation of secretion organic acid transport amino acid transport amine transport acidic amino acid transport negative regulation of organic acid transport regulation of organic acid transport dicarboxylic acid transport regulation of amine transport axonogenesis cell projection organization plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis neurogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis collateral sprouting plasma membrane bounded cell projection organization axon development cell morphogenesis involved in neuron differentiation developmental growth involved in morphogenesis generation of neurons anatomical structure morphogenesis neuron development forebrain development rhythmic process positive regulation of circadian rhythm circadian rhythm positive regulation of biological process regulation of circadian rhythm dendrite development neuron migration	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery sarcolemma plasma membrane membrane membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery sarcolemma plasma membrane membrane membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system acrosomal vesicle intracellular vesicle cytoplasmic vesicle secretory granule secretory vesicle vesicle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR014710	RmlC-like jelly roll fold	Homologous Superfamily
A	IPR018488	Cyclic nucleotide-binding, conserved site	Conserved Site
A	IPR000719	Protein kinase domain	Domain
A	IPR000595	Cyclic nucleotide-binding domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR000961	AGC-kinase, C-terminal	Domain
A	IPR031831	cGMP-dependent protein kinase, N-terminal coiled-coil domain	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR002374	cGMP-dependent kinase	Family
A	IPR018490	Cyclic nucleotide-binding domain superfamily	Homologous Superfamily
A	IPR035014	cGMP-dependent protein kinase, catalytic domain	Domain
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q13976	thoracic aortic aneurysm pulmonary hypertension aortic aneurysm, familial thoracic 8 Sezary syndrome amphetamine abuse non-small cell lung carcinoma malignant colon neoplasm Marfan syndrome osteosarcoma pancreatic intraductal papillary-mucinous neoplasm adrenal cortex carcinoma precancerous condition Amphetamine-Related Disorders attention deficit hyperactivity disorder, inattentive type congenital anemia thoracic aortic aneurysm pulmonary hypertension aortic aneurysm, familial thoracic 8 Sezary syndrome amphetamine abuse non-small cell lung carcinoma malignant colon neoplasm Marfan syndrome osteosarcoma pancreatic intraductal papillary-mucinous neoplasm adrenal cortex carcinoma precancerous condition Amphetamine-Related Disorders attention deficit hyperactivity disorder, inattentive type congenital anemia lung cancer malignant ependymoma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia aortic aneurysm autism spectrum disorder familial thoracic aortic aneurysm and aortic dissection interstitial lung disease lung carcinoma malignant mesothelioma pancreatic intraductal papillary-mucinous carcinoma pituitary cancer cystic fibrosis idiopathic pulmonary fibrosis lung adenocarcinoma

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.