3GIS | pdb_00003gis

Crystal Structure of Na-free Thrombin in Complex with Thrombomodulin

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)
G [auth X]	d3gisx1	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
H [auth Y]	d3gisy1	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
I [auth Z]	d3gisz1	Small proteins	Knottins (small inhibitors, toxins, lectins)	EGF/Laminin	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)
B	SCOP2B Superfamily	Trypsin-like serine proteases	8042154	3000114	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Trypsin-like serine proteases	8042154	3000114	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Trypsin-like serine proteases	8042154	3000114	SCOP2B (2022-06-29)
G [auth X]	SCOP2B Superfamily	EGF/Laminin-like	8038334	3000412	SCOP2B (2022-06-29)
G [auth X]	SCOP2B Superfamily	EGF/Laminin-like	8038333	3000412	SCOP2B (2022-06-29)
G [auth X]	SCOP2B Superfamily	EGF/Laminin-like	8038335	3000412	SCOP2B (2022-06-29)
H [auth Y]	SCOP2B Superfamily	EGF/Laminin-like	8038333	3000412	SCOP2B (2022-06-29)
H [auth Y]	SCOP2B Superfamily	EGF/Laminin-like	8038335	3000412	SCOP2B (2022-06-29)
H [auth Y]	SCOP2B Superfamily	EGF/Laminin-like	8038334	3000412	SCOP2B (2022-06-29)
I [auth Z]	SCOP2B Superfamily	EGF/Laminin-like	8038335	3000412	SCOP2B (2022-06-29)
I [auth Z]	SCOP2B Superfamily	EGF/Laminin-like	8038334	3000412	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)
G [auth X]	Tme5_EGF_like	e3gisX2	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: Tme5_EGF_like	ECOD (1.6)
G [auth X]	EGF_CA	e3gisX3	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: EGF_CA	ECOD (1.6)
H [auth Y]	Tme5_EGF_like	e3gisY5	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: Tme5_EGF_like	ECOD (1.6)
H [auth Y]	EGF_CA	e3gisY4	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: EGF_CA	ECOD (1.6)
I [auth Z]	Tme5_EGF_like	e3gisZ5	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: Tme5_EGF_like	ECOD (1.6)
I [auth Z]	EGF_CA	e3gisZ4	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: EGF_CA	ECOD (1.6)
I [auth Z]	UNK_F_TYPE	e3gisZ1	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: UNK_F_TYPE	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	4.10.140.10	Few Secondary Structures	Irregular	Epsilon-Thrombin	Chain L	CATH (4.3.0)
C	4.10.140.10	Few Secondary Structures	Irregular	Epsilon-Thrombin	Chain L	CATH (4.3.0)
E	4.10.140.10	Few Secondary Structures	Irregular	Epsilon-Thrombin	Chain L	CATH (4.3.0)
B	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
D	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
F	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
G [auth X]	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
H [auth Y]	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)
I [auth Z]	2.10.25.10	Mainly Beta	Ribbon	Laminin	Laminin	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B, D, F	PF00089	Trypsin (Trypsin)	Trypsin		Domain
G [auth X], H [auth Y], I [auth Z]	PF12662	Complement Clr-like EGF-like (cEGF)	Complement Clr-like EGF-like	cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteristic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL recepto ...	cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteristic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C, E	Prothrombin	molecular transducer activity binding molecular function activator activity signaling receptor binding signaling receptor activity growth factor activity signaling receptor activator activity protein binding molecular function regulator activity signaling receptor regulator activity receptor ligand activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity molecular transducer activity binding molecular function activator activity signaling receptor binding signaling receptor activity growth factor activity signaling receptor activator activity protein binding molecular function regulator activity signaling receptor regulator activity receptor ligand activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity cation binding ion binding calcium ion binding metal ion binding small molecule binding lipid binding lipopolysaccharide binding carbohydrate derivative binding thrombospondin receptor activity heparin binding glycosaminoglycan binding sulfur compound binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding biological process involved in interspecies interaction between organisms response to other organism defense response multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding biological process involved in interspecies interaction between organisms response to other organism defense response defense response to symbiont response to external stimulus disruption of cell in another organism response to biotic stimulus biological process involved in symbiotic interaction killing by host of symbiont cells cytolysis by host of symbiont cells defense response to other organism cellular process response to external biotic stimulus disruption of anatomical structure in another organism biological process involved in interaction with symbiont killing of cells of another organism cell killing neutrophil-mediated killing of symbiont cell defense response to Gram-negative bacterium myeloid leukocyte mediated immunity defense response to bacterium neutrophil mediated immunity response to bacterium leukocyte mediated immunity neutrophil-mediated killing of bacterium neutrophil mediated cytotoxicity leukocyte mediated cytotoxicity immune effector process neutrophil-mediated killing of gram-negative bacterium immune system process cellular response to stimulus regulation of biological process regulation of cellular process signaling cell communication thrombin-activated receptor signaling pathway G protein-coupled receptor signaling pathway signal transduction regulation of response to external stimulus negative regulation of biological process regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process regulation of hemostasis negative regulation of response to stimulus negative regulation of wound healing regulation of blood coagulation negative regulation of blood coagulation negative regulation of response to wounding negative regulation of hemostasis fibrinolysis negative regulation of coagulation regulation of response to stimulus negative regulation of response to external stimulus regulation of wound healing negative regulation of multicellular organismal process inorganic ion homeostasis intracellular calcium ion homeostasis homeostatic process calcium ion homeostasis regulation of cytosolic calcium ion concentration cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis cell activation platelet activation acute-phase response inflammatory response acute inflammatory response positive regulation of coagulation positive regulation of biological process positive regulation of blood coagulation positive regulation of response to stimulus positive regulation of hemostasis positive regulation of response to wounding positive regulation of wound healing positive regulation of multicellular organismal process regulation of biosynthetic process collagen biosynthetic process regulation of collagen biosynthetic process regulation of collagen metabolic process positive regulation of metabolic process positive regulation of collagen metabolic process biosynthetic process positive regulation of biosynthetic process positive regulation of collagen biosynthetic process metabolic process collagen metabolic process regulation of metabolic process positive regulation of cellular process regulation of cell activation negative regulation of platelet activation negative regulation of cellular process negative regulation of cell activation regulation of platelet activation regulation of growth regulation of cellular component organization growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular component organization or biogenesis cellular developmental process regulation of developmental process astrocyte differentiation cell development regulation of neurogenesis regulation of cell differentiation regulation of gliogenesis regulation of astrocyte differentiation regulation of cell development regulation of nervous system development multicellular organism development neurogenesis negative regulation of neurogenesis gliogenesis cell differentiation anatomical structure development negative regulation of nervous system development negative regulation of cell differentiation system development developmental process regulation of multicellular organismal development negative regulation of developmental process regulation of glial cell differentiation nervous system development negative regulation of astrocyte differentiation negative regulation of gliogenesis negative regulation of cell development negative regulation of glial cell differentiation central nervous system development glial cell differentiation protein localization regulation of localization cellular localization regulation of protein localization positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization to organelle positive regulation of protein localization negative regulation of proteolysis regulation of protein metabolic process negative regulation of metabolic process primary metabolic process regulation of macromolecule metabolic process regulation of primary metabolic process regulation of proteolysis proteolysis protein metabolic process macromolecule metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction regulation of signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette regulation of signaling positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling reactive oxygen species metabolic process positive regulation of reactive oxygen species metabolic process regulation of reactive oxygen species metabolic process regulation of cell shape cell morphogenesis regulation of cell morphogenesis anatomical structure morphogenesis regulation of anatomical structure morphogenesis cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation phospholipase C-activating G protein-coupled receptor signaling pathway regulation of G protein-coupled receptor signaling pathway positive regulation of G protein-coupled receptor signaling pathway positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway regulation of phospholipase C-activating G protein-coupled receptor signaling pathway positive regulation of response to external stimulus regulation of fibrinolysis negative regulation of fibrinolysis cell surface receptor signaling pathway humoral immune response immune response antimicrobial humoral response antimicrobial humoral immune response mediated by antimicrobial peptide cell surface receptor signaling pathway via STAT positive regulation of receptor signaling pathway via STAT positive regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT regulation of calcium ion transport positive regulation of cation transmembrane transport positive regulation of calcium ion transport calcium ion transport positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport monoatomic cation transport regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol regulation of transmembrane transport transport monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport positive regulation of calcium ion transmembrane transport positive regulation of transmembrane transport monoatomic ion transport positive regulation of release of sequestered calcium ion into cytosol regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol regulation of transport sequestering of calcium ion positive regulation of transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation establishment of protein localization nitrogen compound transport positive regulation of establishment of protein localization positive regulation of insulin secretion regulation of peptide hormone secretion regulation of hormone levels positive regulation of peptide hormone secretion establishment of protein localization to extracellular region protein secretion regulation of protein secretion regulation of secretion regulation of hormone secretion regulation of peptide secretion positive regulation of secretion by cell hormone secretion protein localization to extracellular region positive regulation of protein transport peptide secretion regulation of secretion by cell secretion by cell positive regulation of hormone secretion positive regulation of secretion amide transport signal release positive regulation of peptide secretion secretion regulation of peptide transport regulation of establishment of protein localization export from cell cell-cell signaling regulation of protein transport positive regulation of protein secretion peptide transport protein transport regulation of insulin secretion peptide hormone secretion hormone transport insulin secretion ligand-gated ion channel signaling pathway regulation of cytokine production involved in inflammatory response cytokine production regulation of cytokine production negative regulation of cytokine production involved in inflammatory response production of molecular mediator involved in inflammatory response negative regulation of cytokine production cytokine production involved in inflammatory response gene expression macromolecule biosynthetic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen endoplasmic reticulum cytoplasm plasma membrane membrane Golgi apparatus Golgi lumen blood microparticle
B, D, F	Prothrombin	molecular transducer activity binding molecular function activator activity signaling receptor binding signaling receptor activity growth factor activity signaling receptor activator activity protein binding molecular function regulator activity signaling receptor regulator activity receptor ligand activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity molecular transducer activity binding molecular function activator activity signaling receptor binding signaling receptor activity growth factor activity signaling receptor activator activity protein binding molecular function regulator activity signaling receptor regulator activity receptor ligand activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity cation binding ion binding calcium ion binding metal ion binding small molecule binding lipid binding lipopolysaccharide binding carbohydrate derivative binding thrombospondin receptor activity heparin binding glycosaminoglycan binding sulfur compound binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding biological process involved in interspecies interaction between organisms response to other organism defense response multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding biological process involved in interspecies interaction between organisms response to other organism defense response defense response to symbiont response to external stimulus disruption of cell in another organism response to biotic stimulus biological process involved in symbiotic interaction killing by host of symbiont cells cytolysis by host of symbiont cells defense response to other organism cellular process response to external biotic stimulus disruption of anatomical structure in another organism biological process involved in interaction with symbiont killing of cells of another organism cell killing neutrophil-mediated killing of symbiont cell defense response to Gram-negative bacterium myeloid leukocyte mediated immunity defense response to bacterium neutrophil mediated immunity response to bacterium leukocyte mediated immunity neutrophil-mediated killing of bacterium neutrophil mediated cytotoxicity leukocyte mediated cytotoxicity immune effector process neutrophil-mediated killing of gram-negative bacterium immune system process cellular response to stimulus regulation of biological process regulation of cellular process signaling cell communication thrombin-activated receptor signaling pathway G protein-coupled receptor signaling pathway signal transduction regulation of response to external stimulus negative regulation of biological process regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process regulation of hemostasis negative regulation of response to stimulus negative regulation of wound healing regulation of blood coagulation negative regulation of blood coagulation negative regulation of response to wounding negative regulation of hemostasis fibrinolysis negative regulation of coagulation regulation of response to stimulus negative regulation of response to external stimulus regulation of wound healing negative regulation of multicellular organismal process inorganic ion homeostasis intracellular calcium ion homeostasis homeostatic process calcium ion homeostasis regulation of cytosolic calcium ion concentration cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis cell activation platelet activation acute-phase response inflammatory response acute inflammatory response positive regulation of coagulation positive regulation of biological process positive regulation of blood coagulation positive regulation of response to stimulus positive regulation of hemostasis positive regulation of response to wounding positive regulation of wound healing positive regulation of multicellular organismal process regulation of biosynthetic process collagen biosynthetic process regulation of collagen biosynthetic process regulation of collagen metabolic process positive regulation of metabolic process positive regulation of collagen metabolic process biosynthetic process positive regulation of biosynthetic process positive regulation of collagen biosynthetic process metabolic process collagen metabolic process regulation of metabolic process positive regulation of cellular process regulation of cell activation negative regulation of platelet activation negative regulation of cellular process negative regulation of cell activation regulation of platelet activation regulation of growth regulation of cellular component organization growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular component organization or biogenesis cellular developmental process regulation of developmental process astrocyte differentiation cell development regulation of neurogenesis regulation of cell differentiation regulation of gliogenesis regulation of astrocyte differentiation regulation of cell development regulation of nervous system development multicellular organism development neurogenesis negative regulation of neurogenesis gliogenesis cell differentiation anatomical structure development negative regulation of nervous system development negative regulation of cell differentiation system development developmental process regulation of multicellular organismal development negative regulation of developmental process regulation of glial cell differentiation nervous system development negative regulation of astrocyte differentiation negative regulation of gliogenesis negative regulation of cell development negative regulation of glial cell differentiation central nervous system development glial cell differentiation protein localization regulation of localization cellular localization regulation of protein localization positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization to organelle positive regulation of protein localization negative regulation of proteolysis regulation of protein metabolic process negative regulation of metabolic process primary metabolic process regulation of macromolecule metabolic process regulation of primary metabolic process regulation of proteolysis proteolysis protein metabolic process macromolecule metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction regulation of signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette regulation of signaling positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling reactive oxygen species metabolic process positive regulation of reactive oxygen species metabolic process regulation of reactive oxygen species metabolic process regulation of cell shape cell morphogenesis regulation of cell morphogenesis anatomical structure morphogenesis regulation of anatomical structure morphogenesis cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation phospholipase C-activating G protein-coupled receptor signaling pathway regulation of G protein-coupled receptor signaling pathway positive regulation of G protein-coupled receptor signaling pathway positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway regulation of phospholipase C-activating G protein-coupled receptor signaling pathway positive regulation of response to external stimulus regulation of fibrinolysis negative regulation of fibrinolysis cell surface receptor signaling pathway humoral immune response immune response antimicrobial humoral response antimicrobial humoral immune response mediated by antimicrobial peptide cell surface receptor signaling pathway via STAT positive regulation of receptor signaling pathway via STAT positive regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via JAK-STAT regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT regulation of calcium ion transport positive regulation of cation transmembrane transport positive regulation of calcium ion transport calcium ion transport positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport monoatomic cation transport regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol regulation of transmembrane transport transport monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport positive regulation of calcium ion transmembrane transport positive regulation of transmembrane transport monoatomic ion transport positive regulation of release of sequestered calcium ion into cytosol regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol regulation of transport sequestering of calcium ion positive regulation of transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation establishment of protein localization nitrogen compound transport positive regulation of establishment of protein localization positive regulation of insulin secretion regulation of peptide hormone secretion regulation of hormone levels positive regulation of peptide hormone secretion establishment of protein localization to extracellular region protein secretion regulation of protein secretion regulation of secretion regulation of hormone secretion regulation of peptide secretion positive regulation of secretion by cell hormone secretion protein localization to extracellular region positive regulation of protein transport peptide secretion regulation of secretion by cell secretion by cell positive regulation of hormone secretion positive regulation of secretion amide transport signal release positive regulation of peptide secretion secretion regulation of peptide transport regulation of establishment of protein localization export from cell cell-cell signaling regulation of protein transport positive regulation of protein secretion peptide transport protein transport regulation of insulin secretion peptide hormone secretion hormone transport insulin secretion ligand-gated ion channel signaling pathway regulation of cytokine production involved in inflammatory response cytokine production regulation of cytokine production negative regulation of cytokine production involved in inflammatory response production of molecular mediator involved in inflammatory response negative regulation of cytokine production cytokine production involved in inflammatory response gene expression macromolecule biosynthetic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen endoplasmic reticulum cytoplasm plasma membrane membrane Golgi apparatus Golgi lumen blood microparticle
G [auth X], H [auth Y], I [auth Z]	Thrombomodulin	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding molecular transducer activity signaling receptor activity transmembrane signaling receptor activity	multicellular organismal process regulation of body fluid levels regulation of cellular process response to stimulus regulation of response to external stimulus negative regulation of biological process regulation of cell activation negative regulation of platelet activation regulation of response to wounding regulation of coagulation response to stress regulation of response to stress negative regulation of cellular process coagulation multicellular organismal process regulation of body fluid levels regulation of cellular process response to stimulus regulation of response to external stimulus negative regulation of biological process regulation of cell activation negative regulation of platelet activation regulation of response to wounding regulation of coagulation response to stress regulation of response to stress negative regulation of cellular process coagulation regulation of multicellular organismal process regulation of biological quality response to wounding regulation of hemostasis wound healing regulation of biological process negative regulation of response to stimulus negative regulation of wound healing regulation of blood coagulation negative regulation of blood coagulation biological regulation hemostasis cell activation response to external stimulus negative regulation of response to wounding blood coagulation negative regulation of cell activation negative regulation of hemostasis regulation of platelet activation negative regulation of coagulation regulation of response to stimulus negative regulation of response to external stimulus regulation of wound healing cellular process negative regulation of multicellular organismal process platelet activation multi-multicellular organism process reproductive process female pregnancy multi-organism reproductive process blood coagulation, common pathway protein maturation blood coagulation, fibrin clot formation protein metabolic process protein activation cascade primary metabolic process gene expression macromolecule biosynthetic process biosynthetic process metabolic process macromolecule metabolic process response to X-ray response to ionizing radiation response to radiation response to abiotic stimulus positive regulation of coagulation positive regulation of biological process positive regulation of blood coagulation positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of hemostasis positive regulation of response to wounding positive regulation of wound healing fibrinolysis regulation of fibrinolysis positive regulation of multicellular organismal process negative regulation of fibrinolysis response to chemical response to organophosphorus response to oxygen-containing compound response to nitrogen compound response to purine-containing compound response to cAMP proteolysis zymogen activation protein processing biological process involved in interspecies interaction between organisms response to lipid response to other organism response to lipopolysaccharide response to biotic stimulus response to bacterium response to external biotic stimulus response to molecule of bacterial origin	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane apicolateral plasma membrane plasma membrane region protein-containing complex catalytic complex peptidase complex endopeptidase complex serine-type endopeptidase complex cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane apicolateral plasma membrane plasma membrane region protein-containing complex catalytic complex peptidase complex endopeptidase complex serine-type endopeptidase complex serine-type peptidase complex vacuolar membrane membrane-bounded organelle intracellular anatomical structure vacuole intracellular membrane-bounded organelle intracellular organelle bounding membrane of organelle organelle cytoplasm organelle membrane extracellular region extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C, E	IPR018992	Thrombin light chain	Domain
A, C, E	IPR037111	Thrombin light chain domain superfamily	Homologous Superfamily
A, C, E	IPR003966	Prothrombin/thrombin	Family
A, C, E	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
A, C, E	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, C, E	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
A, C, E	IPR001254	Serine proteases, trypsin domain	Domain
A, C, E	IPR035972	Gamma-carboxyglutamic acid-rich (GLA) domain superfamily	Homologous Superfamily
A, C, E	IPR000001	Kringle	Domain
A, C, E	IPR000294	Gamma-carboxyglutamic acid-rich (GLA) domain	Domain
A, C, E	IPR051659	Serine Protease S1 Domain-Containing Protein	Family
A, C, E	IPR018056	Kringle, conserved site	Conserved Site
A, C, E	IPR013806	Kringle-like fold	Homologous Superfamily
A, C, E	IPR038178	Kringle superfamily	Homologous Superfamily
A, C, E	IPR001314	Peptidase S1A, chymotrypsin family	Family
A, C, E	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
B, D, F	IPR018992	Thrombin light chain	Domain
B, D, F	IPR037111	Thrombin light chain domain superfamily	Homologous Superfamily
B, D, F	IPR003966	Prothrombin/thrombin	Family
B, D, F	IPR018114	Serine proteases, trypsin family, histidine active site	Active Site
B, D, F	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
B, D, F	IPR033116	Serine proteases, trypsin family, serine active site	Active Site
B, D, F	IPR001254	Serine proteases, trypsin domain	Domain
B, D, F	IPR035972	Gamma-carboxyglutamic acid-rich (GLA) domain superfamily	Homologous Superfamily
B, D, F	IPR000001	Kringle	Domain
B, D, F	IPR000294	Gamma-carboxyglutamic acid-rich (GLA) domain	Domain
B, D, F	IPR051659	Serine Protease S1 Domain-Containing Protein	Family
B, D, F	IPR018056	Kringle, conserved site	Conserved Site
B, D, F	IPR013806	Kringle-like fold	Homologous Superfamily
B, D, F	IPR038178	Kringle superfamily	Homologous Superfamily
B, D, F	IPR001314	Peptidase S1A, chymotrypsin family	Family
B, D, F	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
G [auth X], H [auth Y], I [auth Z]	IPR052126	Spindle_Organization_and_Thrombomodulin	Family
G [auth X], H [auth Y], I [auth Z]	IPR016187	C-type lectin fold	Homologous Superfamily
G [auth X], H [auth Y], I [auth Z]	IPR018097	EGF-like calcium-binding, conserved site	Conserved Site
G [auth X], H [auth Y], I [auth Z]	IPR026823	Complement Clr-like EGF domain	Domain
G [auth X], H [auth Y], I [auth Z]	IPR001304	C-type lectin-like	Domain
G [auth X], H [auth Y], I [auth Z]	IPR016186	C-type lectin-like/link domain superfamily	Homologous Superfamily
G [auth X], H [auth Y], I [auth Z]	IPR000742	EGF-like domain	Domain
G [auth X], H [auth Y], I [auth Z]	IPR049883	NOTCH1 EGF-like calcium-binding domain	Domain
G [auth X], H [auth Y], I [auth Z]	IPR015149	Thrombomodulin-like, EGF-like	Domain
G [auth X], H [auth Y], I [auth Z]	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
G [auth X], H [auth Y], I [auth Z]	IPR001881	EGF-like calcium-binding domain	Domain
G [auth X], H [auth Y], I [auth Z]	IPR000152	EGF-type aspartate/asparagine hydroxylation site	PTM

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C, E	Pharos: P00734	congenital prothrombin deficiency thrombophilia pregnancy loss, recurrent, susceptibility to, 2 liver failure cirrhosis of liver Venous Thrombosis intracranial sinus thrombosis brain ischemia myocardial infarction disseminated intravascular coagulation Alzheimer disease rheumatoid arthritis thrombotic disease hepatocellular carcinoma schizophrenia congenital prothrombin deficiency thrombophilia pregnancy loss, recurrent, susceptibility to, 2 liver failure cirrhosis of liver Venous Thrombosis intracranial sinus thrombosis brain ischemia myocardial infarction disseminated intravascular coagulation Alzheimer disease rheumatoid arthritis thrombotic disease hepatocellular carcinoma schizophrenia non-alcoholic fatty liver disease obesity disorder paratuberculosis skin vascular disease cerebrovascular disorder thrombophilia due to thrombin defect nephrosis venous thromboembolism cerebral infarction COVID-19 varicose disease osteoarthritis anemia pulmonary embolism autoimmune disease esophageal varices vascular disease vitamin K deficiency hemorrhagic disease heart disease alcohol abuse hepatic encephalopathy inborn carbohydrate metabolic disorder respiratory failure blood coagulation disease cancer liver disease thrombocytopenia coronary artery disease fatty liver disease hemochromatosis type 1 pneumonia hepatitis B virus infection hypertensive disorder autism spectrum disorder kidney disease
B, D, F	Pharos: P00734	congenital prothrombin deficiency thrombophilia pregnancy loss, recurrent, susceptibility to, 2 liver failure cirrhosis of liver Venous Thrombosis intracranial sinus thrombosis brain ischemia myocardial infarction disseminated intravascular coagulation Alzheimer disease rheumatoid arthritis thrombotic disease hepatocellular carcinoma schizophrenia congenital prothrombin deficiency thrombophilia pregnancy loss, recurrent, susceptibility to, 2 liver failure cirrhosis of liver Venous Thrombosis intracranial sinus thrombosis brain ischemia myocardial infarction disseminated intravascular coagulation Alzheimer disease rheumatoid arthritis thrombotic disease hepatocellular carcinoma schizophrenia non-alcoholic fatty liver disease obesity disorder paratuberculosis skin vascular disease cerebrovascular disorder thrombophilia due to thrombin defect nephrosis venous thromboembolism cerebral infarction COVID-19 varicose disease osteoarthritis anemia pulmonary embolism autoimmune disease esophageal varices vascular disease vitamin K deficiency hemorrhagic disease heart disease alcohol abuse hepatic encephalopathy inborn carbohydrate metabolic disorder respiratory failure blood coagulation disease cancer liver disease thrombocytopenia coronary artery disease fatty liver disease hemochromatosis type 1 pneumonia hepatitis B virus infection hypertensive disorder autism spectrum disorder kidney disease
G [auth X], H [auth Y], I [auth Z]	Pharos: P07204	thrombophilia atypical hemolytic-uremic syndrome thrombomodulin-related bleeding disorder thrombotic thrombocytopenic purpura acute promyelocytic leukemia adult acute respiratory distress syndrome pulmonary embolism myocardial infarction hemolytic-uremic syndrome neuropathy, painful disseminated intravascular coagulation Liver Cirrhosis, Experimental atypical hemolytic-uremic syndrome with thrombomodulin anomaly thrombotic disease gastric cancer thrombophilia atypical hemolytic-uremic syndrome thrombomodulin-related bleeding disorder thrombotic thrombocytopenic purpura acute promyelocytic leukemia adult acute respiratory distress syndrome pulmonary embolism myocardial infarction hemolytic-uremic syndrome neuropathy, painful disseminated intravascular coagulation Liver Cirrhosis, Experimental atypical hemolytic-uremic syndrome with thrombomodulin anomaly thrombotic disease gastric cancer vascular disease interstitial cystitis lung cancer pancreatic intraductal papillary-mucinous carcinoma breast carcinoma psoriasis hemolytic anemia hereditary diffuse gastric adenocarcinoma lung carcinoma adenoma medulloblastoma non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia congenital thrombotic thrombocytopenic purpura ulcerative colitis lung adenocarcinoma adrenal cortex carcinoma ovarian cancer breast cancer pituitary cancer cystic fibrosis gastric neoplasm