4NI2

Crystal structure of the heterodimeric catalytic domain of wild-type human soluble guanylate cyclase

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	d4ni2b_	Alpha and beta proteins (a+b)	Ferredoxin-like	Nucleotide cyclase	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	Adenylyl and guanylyl cyclase catalytic domain	8064535	4001316	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Nucleotide cyclase/DNA polymerase palm domain-like	8064536	3001272	SCOP2 (2022-06-29)
B	SCOP2 Family	Adenylyl and guanylyl cyclase catalytic domain	8064543	4001316	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	Nucleotide cyclase/DNA polymerase palm domain-like	8064544	3001272	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	PF00211	e4ni2A1	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: PF00211	ECOD (1.6)
B	PF00211	e4ni2B1	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: PF00211	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.70.1230	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Nucleotide cyclase, GGDEF domain	CATH (4.3.0)
B	3.30.70.1230	Alpha Beta	2-Layer Sandwich	Alpha-Beta Plaits	Nucleotide cyclase, GGDEF domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00211	Adenylate and Guanylate cyclase catalytic domain (Guanylate_cyc)	Adenylate and Guanylate cyclase catalytic domain	-	Domain
B	PF00211	Adenylate and Guanylate cyclase catalytic domain (Guanylate_cyc)	Adenylate and Guanylate cyclase catalytic domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Guanylate cyclase soluble subunit alpha-3	molecular transducer activity signaling receptor activity binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding molecular transducer activity signaling receptor activity binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding tetrapyrrole binding heme binding phosphorus-oxygen lyase activity cyclase activity lyase activity guanylate cyclase activity catalytic activity	multicellular organismal process system process circulatory system process regulation of blood pressure biological regulation regulation of biological quality blood circulation cellular response to stimulus nitric oxide mediated signal transduction regulation of biological process regulation of cellular process response to stimulus signaling intracellular signal transduction multicellular organismal process system process circulatory system process regulation of blood pressure biological regulation regulation of biological quality blood circulation cellular response to stimulus nitric oxide mediated signal transduction regulation of biological process regulation of cellular process response to stimulus signaling intracellular signal transduction cell communication intracellular signaling cassette cellular process signal transduction positive regulation of cell communication positive regulation of signal transduction positive regulation of biological process regulation of signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of cellular process regulation of signaling regulation of nitric oxide mediated signal transduction positive regulation of intracellular signal transduction positive regulation of nitric oxide mediated signal transduction regulation of response to stimulus regulation of cell communication positive regulation of signaling regulation of system process negative regulation of biological process negative regulation of muscle contraction smooth muscle contraction regulation of smooth muscle contraction regulation of multicellular organismal process blood vessel diameter maintenance negative regulation of smooth muscle contraction regulation of tube diameter relaxation of smooth muscle regulation of tube size 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 cGMP-mediated signaling nitric oxide-cGMP-mediated signaling response to oxygen levels response to abiotic stimulus trans-synaptic signaling, modulating synaptic transmission modulation of chemical synaptic transmission retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission synaptic signaling retrograde trans-synaptic signaling by nitric oxide synaptic signaling by nitric oxide trans-synaptic signaling retrograde trans-synaptic signaling cell-cell signaling retrograde trans-synaptic signaling by soluble gas trans-synaptic signaling by soluble gas, modulating synaptic transmission chemical synaptic transmission trans-synaptic signaling by nitric oxide regulation of trans-synaptic signaling trans-synaptic signaling by nitric oxide, modulating synaptic transmission anterograde trans-synaptic signaling trans-synaptic signaling by soluble gas ribose phosphate metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process cyclic nucleotide metabolic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process purine nucleotide metabolic process organic substance metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process cyclic nucleotide biosynthetic process phosphate-containing compound metabolic process organic substance biosynthetic process small molecule metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process cyclic purine nucleotide metabolic process cellular metabolic process primary metabolic process nucleotide metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process organic cyclic compound metabolic process biosynthetic process cGMP metabolic process organophosphate metabolic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process metabolic process purine ribonucleotide metabolic process cGMP biosynthetic process purine nucleotide biosynthetic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol guanylate cyclase complex, soluble protein-containing complex catalytic complex GABA-ergic synapse synapse cell junction glutamatergic synapse
B	Guanylate cyclase soluble subunit beta-1	molecular transducer activity signaling receptor activity phosphorus-oxygen lyase activity cyclase activity lyase activity adenylate cyclase activity catalytic activity Hsp90 protein binding protein binding binding heat shock protein binding cytidylate cyclase activity guanyl nucleotide binding GTP binding molecular transducer activity signaling receptor activity phosphorus-oxygen lyase activity cyclase activity lyase activity adenylate cyclase activity catalytic activity Hsp90 protein binding protein binding binding heat shock protein binding cytidylate cyclase activity guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding protein-containing complex binding tetrapyrrole binding heme binding guanylate cyclase activity cation binding metal ion binding	cellular response to stimulus nitric oxide mediated signal transduction regulation of biological process regulation of cellular process response to stimulus signaling biological regulation intracellular signal transduction cell communication intracellular signaling cassette cellular process signal transduction trans-synaptic signaling regulation of signaling cellular response to stimulus nitric oxide mediated signal transduction regulation of biological process regulation of cellular process response to stimulus signaling biological regulation intracellular signal transduction cell communication intracellular signaling cassette cellular process signal transduction trans-synaptic signaling regulation of signaling trans-synaptic signaling, modulating synaptic transmission modulation of chemical synaptic transmission cell-cell signaling trans-synaptic signaling by soluble gas, modulating synaptic transmission chemical synaptic transmission synaptic signaling trans-synaptic signaling by nitric oxide regulation of trans-synaptic signaling trans-synaptic signaling by nitric oxide, modulating synaptic transmission anterograde trans-synaptic signaling regulation of cell communication synaptic signaling by nitric oxide trans-synaptic signaling by soluble gas cGMP-mediated signaling nitric oxide-cGMP-mediated signaling response to oxygen levels response to abiotic stimulus ribose phosphate metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process cyclic nucleotide metabolic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process purine nucleotide metabolic process organic substance metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process cyclic nucleotide biosynthetic process phosphate-containing compound metabolic process organic substance biosynthetic process small molecule metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process cyclic purine nucleotide metabolic process cellular metabolic process primary metabolic process nucleotide metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process organic cyclic compound metabolic process biosynthetic process cGMP metabolic process organophosphate metabolic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process metabolic process purine ribonucleotide metabolic process cGMP biosynthetic process purine nucleotide biosynthetic process cellular response to nitrogen compound cellular response to inorganic substance response to oxygen-containing compound response to nitrogen compound cellular response to oxygen-containing compound response to inorganic substance cellular response to nitric oxide cellular response to chemical stimulus response to chemical response to nitric oxide cellular response to reactive nitrogen species multicellular organismal process system process circulatory system process blood circulation	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol guanylate cyclase complex, soluble protein-containing complex catalytic complex cell cortex synapse cytoplasmic region presynaptic active zone cytoplasmic component cell periphery presynapse cell junction intracellular anatomical structure cytoplasm cellular anatomical entity cytosol guanylate cyclase complex, soluble protein-containing complex catalytic complex cell cortex synapse cytoplasmic region presynaptic active zone cytoplasmic component cell periphery presynapse cell junction cell cortex region presynaptic active zone glutamatergic synapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR038158	H-NOX domain superfamily	Homologous Superfamily
A	IPR024096	NO signalling/Golgi transport ligand-binding domain superfamily	Homologous Superfamily
A	IPR001054	Adenylyl cyclase class-3/4/guanylyl cyclase	Domain
A	IPR042463	Haem NO binding associated domain superfamily	Homologous Superfamily
A	IPR029787	Nucleotide cyclase	Homologous Superfamily
A	IPR018297	Adenylyl cyclase class-4/guanylyl cyclase, conserved site	Conserved Site
A	IPR011645	Haem NO binding associated	Domain
B	IPR038158	H-NOX domain superfamily	Homologous Superfamily
B	IPR024096	NO signalling/Golgi transport ligand-binding domain superfamily	Homologous Superfamily
B	IPR001054	Adenylyl cyclase class-3/4/guanylyl cyclase	Domain
B	IPR042463	Haem NO binding associated domain superfamily	Homologous Superfamily
B	IPR029787	Nucleotide cyclase	Homologous Superfamily
B	IPR018297	Adenylyl cyclase class-4/guanylyl cyclase, conserved site	Conserved Site
B	IPR011644	Heme NO-binding	Domain
B	IPR011645	Haem NO binding associated	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q02108	hypertensive disorder malignant colon neoplasm Moyamoya disease with early-onset achalasia coronary artery disease salivary gland adenoid cystic carcinoma adenoid cystic carcinoma salivary gland cancer heart disease Thrombosis tuberculosis large cell medulloblastoma malignant glioma alveolar capillary dysplasia with misalignment of pulmonary veins medulloblastoma astrocytic tumor hypertensive disorder malignant colon neoplasm Moyamoya disease with early-onset achalasia coronary artery disease salivary gland adenoid cystic carcinoma adenoid cystic carcinoma salivary gland cancer heart disease Thrombosis tuberculosis large cell medulloblastoma malignant glioma alveolar capillary dysplasia with misalignment of pulmonary veins medulloblastoma astrocytic tumor myocardial infarction ovarian cancer breast cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia colonic neoplasm pilocytic astrocytoma pulmonary hypertension gastric carcinoma thrombotic disease ulcerative colitis malignant ependymoma Moyamoya disease non-small cell lung carcinoma atypical teratoid rhabdoid tumor pancreatic ductal adenocarcinoma breast carcinoma progressive supranuclear palsy glioblastoma spina bifida interstitial cystitis lung cancer malignant essential hypertension malignant pancreatic neoplasm osteosarcoma benign colon neoplasm pancreatic intraductal papillary-mucinous carcinoma Pick disease pulmonary edema of mountaineers, susceptibility to exocrine pancreatic carcinoma
B	Pharos: Q02153	hypertensive disorder large cell medulloblastoma malignant colon neoplasm malignant glioma medulloblastoma Acute exacerbation of chronic congestive heart failure ovarian cancer alveolar capillary dysplasia with misalignment of pulmonary veins Parkinson disease astrocytic tumor pilocytic astrocytoma pulmonary hypertension ulcerative colitis glioblastoma malignant ependymoma hypertensive disorder large cell medulloblastoma malignant colon neoplasm malignant glioma medulloblastoma Acute exacerbation of chronic congestive heart failure ovarian cancer alveolar capillary dysplasia with misalignment of pulmonary veins Parkinson disease astrocytic tumor pilocytic astrocytoma pulmonary hypertension ulcerative colitis glioblastoma malignant ependymoma malignant mesothelioma myocardial infarction pancreatic intraductal papillary-mucinous carcinoma primitive neuroectodermal tumor atypical teratoid rhabdoid tumor Sjogren syndrome congestive heart failure exocrine pancreatic carcinoma heart disease interstitial cystitis lung cancer malignant essential hypertension malignant pancreatic neoplasm oligodendroglioma acute myeloid leukemia pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Pick disease pulmonary arterial hypertension tuberculosis gastric carcinoma

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 R01GM133198.