5COX

UNINHIBITED MOUSE CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2)

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
Structure Motif: Primary M-CSA Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d5coxa1	All alpha proteins	Heme-dependent peroxidases	Heme-dependent peroxidases	Myeloperoxidase-like	Prostaglandin H2 synthase	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
A	d5coxa2	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Prostaglandin H2 synthase-1, EGF-like module	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d5coxd1	All alpha proteins	Heme-dependent peroxidases	Heme-dependent peroxidases	Myeloperoxidase-like	Prostaglandin H2 synthase	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d5coxd2	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Prostaglandin H2 synthase-1, EGF-like module	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
B	d5coxb1	All alpha proteins	Heme-dependent peroxidases	Heme-dependent peroxidases	Myeloperoxidase-like	Prostaglandin H2 synthase	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
B	d5coxb2	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Prostaglandin H2 synthase-1, EGF-like module	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
C	d5coxc1	All alpha proteins	Heme-dependent peroxidases	Heme-dependent peroxidases	Myeloperoxidase-like	Prostaglandin H2 synthase	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
C	d5coxc2	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	EGF-type module	Prostaglandin H2 synthase-1, EGF-like module	house mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Heme-dependent peroxidases	8038293	3000844	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	EGF/Laminin-like	8038309	3000412	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	EGF/Laminin-like	8038309	3000412	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Heme-dependent peroxidases	8038293	3000844	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Heme-dependent peroxidases	8038293	3000844	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	EGF/Laminin-like	8038309	3000412	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	EGF/Laminin-like	8038309	3000412	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Heme-dependent peroxidases	8038293	3000844	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	An_peroxidase	e5coxA1	A: alpha complex topology	X: Heme-dependent peroxidases (From Topology)	H: Heme-dependent peroxidases (From Topology)	T: Heme-dependent peroxidases	F: An_peroxidase	ECOD (1.6)
A	hEGF_4	e5coxA2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_4	ECOD (1.6)
D	An_peroxidase	e5coxD1	A: alpha complex topology	X: Heme-dependent peroxidases (From Topology)	H: Heme-dependent peroxidases (From Topology)	T: Heme-dependent peroxidases	F: An_peroxidase	ECOD (1.6)
D	hEGF_4	e5coxD2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_4	ECOD (1.6)
B	An_peroxidase	e5coxB1	A: alpha complex topology	X: Heme-dependent peroxidases (From Topology)	H: Heme-dependent peroxidases (From Topology)	T: Heme-dependent peroxidases	F: An_peroxidase	ECOD (1.6)
B	hEGF_4	e5coxB2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_4	ECOD (1.6)
C	An_peroxidase	e5coxC1	A: alpha complex topology	X: Heme-dependent peroxidases (From Topology)	H: Heme-dependent peroxidases (From Topology)	T: Heme-dependent peroxidases	F: An_peroxidase	ECOD (1.6)
C	hEGF_4	e5coxC2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: hEGF_4	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
A	1.10.640.10	Mainly Alpha	Orthogonal Bundle	Myeloperoxidase, subunit C	Haem peroxidase domain superfamily, animal type	CATH (4.3.0)
D	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
D	1.10.640.10	Mainly Alpha	Orthogonal Bundle	Myeloperoxidase, subunit C	Haem peroxidase domain superfamily, animal type	CATH (4.3.0)
B	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
B	1.10.640.10	Mainly Alpha	Orthogonal Bundle	Myeloperoxidase, subunit C	Haem peroxidase domain superfamily, animal type	CATH (4.3.0)
C	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
C	1.10.640.10	Mainly Alpha	Orthogonal Bundle	Myeloperoxidase, subunit C	Haem peroxidase domain superfamily, animal type	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF00008	EGF-like domain (EGF)	EGF-like domain	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is t ...	There is no clear separation between noise and signal. Pfam:PF00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.	Domain
A, B, C, D	PF03098	Animal haem peroxidase (An_peroxidase)	Animal haem peroxidase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	CYCLOOXYGENASE-2	peroxidase activity oxidoreductase activity antioxidant activity oxidoreductase activity, acting on peroxide as acceptor catalytic activity oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen oxidoreductase activity, acting on single donors with incorporation of molecular oxygen dioxygenase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen prostaglandin-endoperoxide synthase activity cation binding ion binding binding metal ion binding peroxidase activity oxidoreductase activity antioxidant activity oxidoreductase activity, acting on peroxide as acceptor catalytic activity oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen oxidoreductase activity, acting on single donors with incorporation of molecular oxygen dioxygenase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen prostaglandin-endoperoxide synthase activity cation binding ion binding binding metal ion binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity organic cyclic compound binding tetrapyrrole binding heme binding enzyme binding	regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process cellular process regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process cellular process metabolic process regulation of nitric oxide metabolic process positive regulation of nitric oxide biosynthetic process regulation of metabolic process positive regulation of cellular process regulation of transforming growth factor beta production multicellular organismal process positive regulation of macromolecule biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process positive regulation of macromolecule metabolic process transforming growth factor beta production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process macromolecule metabolic process positive regulation of transforming growth factor beta production positive regulation of cytokine production response to stimulus response to chemical response to xenobiotic stimulus positive regulation of platelet-derived growth factor production platelet-derived growth factor production regulation of platelet-derived growth factor production system process circulatory system process regulation of blood pressure regulation of biological quality blood circulation behavior learning learning or memory nervous system process cognition developmental process ossification bone mineralization animal organ development anatomical structure development biomineral tissue development tissue development regulation of tube diameter regulation of tube size regulation of system process positive regulation of vasoconstriction regulation of blood circulation vascular process in circulatory system regulation of vasoconstriction blood vessel diameter maintenance vasoconstriction regulation of anatomical structure size response to decreased oxygen levels cellular response to stimulus cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to oxygen levels response to abiotic stimulus cellular response to heat response to heat response to temperature stimulus prostaglandin transport transport signaling cell communication localization secretion by cell monocarboxylic acid transport fatty acid transport icosanoid transport signal release prostaglandin secretion icosanoid secretion organic anion transport carboxylic acid transport secretion cell-cell signaling export from cell lipid localization lipid transport establishment of localization organic acid transport lipid export from cell macromolecule localization regulation of defense response regulation of response to external stimulus defense response regulation of inflammatory response response to external stimulus regulation of response to stimulus regulation of response to stress regulation of neuroinflammatory response inflammatory response neuroinflammatory response negative regulation of cellular process negative regulation of biological process negative regulation of cell cycle cell cycle regulation of cell cycle positive regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process programmed cell death response to angiotensin response to hormone response to endogenous stimulus response to peptide hormone response to oxygen-containing compound response to nitrogen compound positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation biological process involved in interspecies interaction between organisms response to other organism response to external biotic stimulus response to nematode response to biotic stimulus memory regulation of synaptic plasticity trans-synaptic signaling regulation of signaling modulation of chemical synaptic transmission chemical synaptic transmission positive regulation of synaptic plasticity synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication response to hexose response to monosaccharide response to carbohydrate response to fructose protein localization regulation of localization cellular localization establishment of protein localization nitrogen compound transport regulation of protein localization nucleocytoplasmic transport positive regulation of nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization regulation of protein localization to nucleus positive regulation of protein transport import into nucleus regulation of protein import into nucleus cellular macromolecule localization establishment of localization in cell protein import into nucleus positive regulation of intracellular transport regulation of intracellular transport regulation of transport positive regulation of protein localization to nucleus regulation of establishment of protein localization positive regulation of protein import into nucleus intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus regulation of protein transport positive regulation of transport establishment of protein localization to organelle regulation of cellular localization protein transport protein localization to organelle positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport regulation of calcium ion transport negative regulation of monoatomic ion transport regulation of monoatomic ion transport negative regulation of transport calcium ion transport metal ion transport negative regulation of calcium ion transport monoatomic ion transport monoatomic cation transport regulation of metal ion transport prostaglandin metabolic process unsaturated fatty acid metabolic process oxoacid metabolic process regulation of lipid metabolic process organic acid biosynthetic process organic acid metabolic process carboxylic acid biosynthetic process regulation of small molecule metabolic process positive regulation of lipid metabolic process positive regulation of prostaglandin biosynthetic process small molecule metabolic process prostaglandin biosynthetic process regulation of ketone metabolic process regulation of fatty acid metabolic process regulation of fatty acid biosynthetic process monocarboxylic acid metabolic process positive regulation of unsaturated fatty acid biosynthetic process regulation of prostaglandin biosynthetic process icosanoid metabolic process ketone metabolic process regulation of unsaturated fatty acid biosynthetic process lipid biosynthetic process positive regulation of fatty acid biosynthetic process prostanoid metabolic process icosanoid biosynthetic process prostanoid biosynthetic process positive regulation of fatty acid metabolic process fatty acid metabolic process monocarboxylic acid biosynthetic process small molecule biosynthetic process carboxylic acid metabolic process fatty acid biosynthetic process unsaturated fatty acid biosynthetic process positive regulation of lipid biosynthetic process regulation of lipid biosynthetic process positive regulation of small molecule metabolic process lipid metabolic process response to fluid shear stress cellular response to fluid shear stress regulation of cellular response to stress regulation of signal transduction intracellular signal transduction cellular response to environmental stimulus regulation of response to osmotic stress regulation of cellular response to osmotic stress negative regulation of apoptotic signaling pathway signal transduction intrinsic apoptotic signaling pathway negative regulation of programmed cell death regulation of intrinsic apoptotic signaling pathway in response to osmotic stress negative regulation of apoptotic process intrinsic apoptotic signaling pathway in response to osmotic stress cellular response to abiotic stimulus regulation of apoptotic signaling pathway negative regulation of signaling negative regulation of intracellular signal transduction cellular response to chemical stress regulation of intrinsic apoptotic signaling pathway negative regulation of cell communication regulation of intracellular signal transduction negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress response to osmotic stress negative regulation of response to stimulus cellular response to osmotic stress negative regulation of signal transduction apoptotic signaling pathway negative regulation of intrinsic apoptotic signaling pathway cell population proliferation regulation of smooth muscle cell proliferation positive regulation of cell population proliferation smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation fat cell differentiation cellular developmental process brown fat cell differentiation cell differentiation cellular response to nitrogen compound cellular response to ATP response to organophosphorus cellular response to organic cyclic compound response to ATP response to purine-containing compound cellular response to oxygen-containing compound response to organic cyclic compound muscle contraction muscle system process regulation of muscle system process negative regulation of muscle contraction smooth muscle contraction regulation of smooth muscle contraction regulation of muscle contraction negative regulation of smooth muscle contraction negative regulation of multicellular organismal process positive regulation of locomotion regulation of cell motility cell migration involved in sprouting angiogenesis regulation of blood vessel endothelial cell migration endothelial cell migration angiogenesis positive regulation of cell migration multicellular organism development tube morphogenesis positive regulation of cell motility regulation of cell migration blood vessel endothelial cell migration regulation of endothelial cell migration cell migration positive regulation of cell migration involved in sprouting angiogenesis cell motility locomotion blood vessel development system development blood vessel morphogenesis tube development regulation of cell migration involved in sprouting angiogenesis sprouting angiogenesis vasculature development circulatory system development positive regulation of blood vessel endothelial cell migration anatomical structure morphogenesis regulation of locomotion positive regulation of endothelial cell migration anatomical structure formation involved in morphogenesis regulation of fibroblast growth factor production positive regulation of fibroblast growth factor production fibroblast growth factor production epithelium development epidermal cell differentiation epidermis development epithelial cell differentiation skin development keratinocyte differentiation response to metal ion response to manganese ion regulation of vascular endothelial growth factor production vascular endothelial growth factor production positive regulation of vascular endothelial growth factor production positive regulation of cell communication synaptic transmission, glutamatergic regulation of synaptic transmission, glutamatergic positive regulation of synaptic transmission positive regulation of synaptic transmission, glutamatergic positive regulation of signaling cellular response to non-ionic osmotic stress response to non-ionic osmotic stress response to peptide response to cytokine response to corticosteroid response to lipid response to steroid hormone response to glucocorticoid cellular response to acid chemical cellular response to amino acid stimulus cellular response to homocysteine response to amino acid response to homocysteine response to acid chemical multi-multicellular organism process reproductive process female pregnancy embryo implantation multi-organism reproductive process response to mechanical stimulus cellular response to mechanical stimulus cellular response to external stimulus negative regulation of cell population proliferation placenta development maternal process involved in female pregnancy multicellular organismal reproductive process developmental process involved in reproduction maternal placenta development decidualization positive regulation of brown fat cell differentiation positive regulation of fat cell differentiation regulation of developmental process regulation of cell differentiation regulation of brown fat cell differentiation positive regulation of developmental process positive regulation of cell differentiation regulation of fat cell differentiation response to nutrient levels response to vitamin D response to nutrient response to vitamin positive regulation of smooth muscle contraction positive regulation of muscle contraction hair cycle molting cycle maintenance of blood-brain barrier multicellular organismal-level homeostasis homeostatic process anatomical structure homeostasis tissue homeostasis response to fatty acid negative regulation of synaptic transmission, dopaminergic negative regulation of synaptic transmission regulation of synaptic transmission, dopaminergic synaptic transmission, dopaminergic arachidonate metabolic process long-chain fatty acid metabolic process cyclooxygenase pathway olefinic compound metabolic process response to oxidative stress cellular response to metal ion cellular response to lead ion response to lead ion response to lipopolysaccharide response to bacterium response to molecule of bacterial origin acute-phase response regulation of heat generation positive regulation of heat generation positive regulation of acute inflammatory response heat generation positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response positive regulation of fever generation acute inflammatory response fever generation positive regulation of defense response temperature homeostasis regulation of acute inflammatory response regulation of fever generation response to estradiol response to tumor necrosis factor	cellular anatomical structure intracellular anatomical structure cytoplasm cell projection neuron projection plasma membrane bounded cell projection membrane-bounded organelle organelle inner membrane nuclear membrane membrane nucleus intracellular membrane-bounded organelle endomembrane system intracellular organelle cellular anatomical structure intracellular anatomical structure cytoplasm cell projection neuron projection plasma membrane bounded cell projection membrane-bounded organelle organelle inner membrane nuclear membrane membrane nucleus intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope organelle nuclear inner membrane nuclear envelope organelle membrane membrane microdomain cell periphery membrane raft plasma membrane raft plasma membrane plasma membrane region caveola protein-containing complex organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane nuclear outer membrane organelle outer membrane bounding membrane of organelle outer membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR019791	Haem peroxidase, animal-type	Family
A, B, C, D	IPR050783	Oxylipin biosynthesis and metabolism	Family
A, B, C, D	IPR037120	Haem peroxidase domain superfamily, animal type	Homologous Superfamily
A, B, C, D	IPR010255	Haem peroxidase superfamily	Homologous Superfamily
A, B, C, D	IPR000742	EGF-like domain	Domain

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	prostaglandin-endoperoxide synthase M-CSA #37	Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis. Production of prostaglandin hormones in vertebrates depends on this enzyme, which couples the reduction of dangerous hydroperoxides to the generation of a useful oxidised product. The cofactor which makes this possible is a single iron protoporphyrin IX; its interactions with protein ligands are essential for modulating protein function.	Defined by 7 residues: GLN:A-172 [auth A-203]HIS:A-176 [auth A-207]LEU:A-353 [auth A-384]TYR:A-354 [auth A-385]HIS:A-357 [auth A-388]GLY:A-495 [auth A-526]SER:A-499 [auth A-530] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 1.14.99.1 (PDB Primary Data) Search M-CSA Motif + EC 1.14.99.1

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.