P15306 · TRBM_MOUSE
- ProteinThrombomodulin
- GeneThbd
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids577 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis. Acts as a cofactor for thrombin activation of protein C/PROC on the surface of vascular endothelial cells leading to initiation of the activated protein C anticoagulant pathway. Also accelerates the activation of the plasma carboxypeptidase B2/CPB2, which catalyzes removal of C-terminal basic amino acids from its substrates including kinins or anaphylatoxins leading to fibrinolysis inhibition (By similarity).
Plays critical protective roles in changing the cleavage specificity of protease-activated receptor 1/PAR1, inhibiting endothelial cell permeability and inflammation (PubMed:38174561).
Suppresses inflammation distinctly from its anticoagulant cofactor activity by sequestering HMGB1 thereby preventing it from engaging cellular receptors such as RAGE and contributing to the inflammatory response (By similarity).
Plays critical protective roles in changing the cleavage specificity of protease-activated receptor 1/PAR1, inhibiting endothelial cell permeability and inflammation (PubMed:38174561).
Suppresses inflammation distinctly from its anticoagulant cofactor activity by sequestering HMGB1 thereby preventing it from engaging cellular receptors such as RAGE and contributing to the inflammatory response (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | apicolateral plasma membrane | |
Cellular Component | external side of plasma membrane | |
Cellular Component | extracellular space | |
Cellular Component | plasma membrane | |
Cellular Component | serine-type endopeptidase complex | |
Cellular Component | vacuolar membrane | |
Molecular Function | calcium ion binding | |
Molecular Function | transmembrane signaling receptor activity | |
Biological Process | blood coagulation | |
Biological Process | female pregnancy | |
Biological Process | negative regulation of coagulation | |
Biological Process | response to cAMP | |
Biological Process | response to lipopolysaccharide | |
Biological Process | response to X-ray |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameThrombomodulin
- Short namesTM
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP15306
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 17-517 | Extracellular | ||||
Sequence: LSALAKLQPTGSQCVEHECFALFQGPATFLDASQACQRLQGHLMTVRSSVAADVISLLLSQSSMDLGPWIGLQLPQGCDDPVHLGPLRGFQWVTGDNHTSYSRWARPNDQTAPLCGPLCVTVSTATEAAPGEPAWEEKPCETETQGFLCEFYFTASCRPLTVNTRDPEAAHISSTYNTPFGVSGADFQTLPVGSSAAVEPLGLELVCRAPPGTSEGHWAWEATGAWNCSVENGGCEYLCNRSTNEPRCLCPRDMDLQADGRSCARPVVQSCNELCEHFCVSNAEVPGSYSCMCETGYQLAADGHRCEDVDDCKQGPNPCPQLCVNTKGGFECFCYDGYELVDGECVELLDPCFGSNCEFQCQPVSPTDYRCICAPGFAPKPDEPHKCEMFCNETSCPADCDPNSPTVCECPEGFILDEGSVCTDIDECSQGECFTSECRNFPGSYECICGPDTALAGQISKDCDPIPVREDTKEEEGSGEPPVSPTPGSPTGPPSARPVHS | ||||||
Transmembrane | 518-541 | Helical | ||||
Sequence: GVLIGISIASLSLVVALLALLCHL | ||||||
Topological domain | 542-577 | Cytoplasmic | ||||
Sequence: RKKQGAARAELEYKCASSAKEVVLQHVRTDRTLQKF |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Thbd-deficient embryos die before embryonic day 9.5. An overall retardation in growth and development starts on embryonic day 8.5 (PubMed:7846065).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 28 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-16 | |||||
Sequence: MLGIFFLGVLAPASLG | ||||||
Chain | PRO_0000007772 | 17-577 | Thrombomodulin | |||
Sequence: LSALAKLQPTGSQCVEHECFALFQGPATFLDASQACQRLQGHLMTVRSSVAADVISLLLSQSSMDLGPWIGLQLPQGCDDPVHLGPLRGFQWVTGDNHTSYSRWARPNDQTAPLCGPLCVTVSTATEAAPGEPAWEEKPCETETQGFLCEFYFTASCRPLTVNTRDPEAAHISSTYNTPFGVSGADFQTLPVGSSAAVEPLGLELVCRAPPGTSEGHWAWEATGAWNCSVENGGCEYLCNRSTNEPRCLCPRDMDLQADGRSCARPVVQSCNELCEHFCVSNAEVPGSYSCMCETGYQLAADGHRCEDVDDCKQGPNPCPQLCVNTKGGFECFCYDGYELVDGECVELLDPCFGSNCEFQCQPVSPTDYRCICAPGFAPKPDEPHKCEMFCNETSCPADCDPNSPTVCECPEGFILDEGSVCTDIDECSQGECFTSECRNFPGSYECICGPDTALAGQISKDCDPIPVREDTKEEEGSGEPPVSPTPGSPTGPPSARPVHSGVLIGISIASLSLVVALLALLCHLRKKQGAARAELEYKCASSAKEVVLQHVRTDRTLQKF | ||||||
Glycosylation | 113 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 135↔156 | |||||
Sequence: CVTVSTATEAAPGEPAWEEKPC | ||||||
Glycosylation | 243 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 244↔255 | |||||
Sequence: CSVENGGCEYLC | ||||||
Disulfide bond | 251↔264 | |||||
Sequence: CEYLCNRSTNEPRC | ||||||
Glycosylation | 256 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 266↔279 | |||||
Sequence: CPRDMDLQADGRSC | ||||||
Disulfide bond | 287↔295 | |||||
Sequence: CNELCEHFC | ||||||
Disulfide bond | 291↔307 | |||||
Sequence: CEHFCVSNAEVPGSYSC | ||||||
Disulfide bond | 309↔322 | |||||
Sequence: CETGYQLAADGHRC | ||||||
Disulfide bond | 328↔339 | |||||
Sequence: CKQGPNPCPQLC | ||||||
Disulfide bond | 335↔348 | |||||
Sequence: CPQLCVNTKGGFEC | ||||||
Disulfide bond | 350↔361 | |||||
Sequence: CYDGYELVDGEC | ||||||
Disulfide bond | 368↔377 | |||||
Sequence: CFGSNCEFQC | ||||||
Disulfide bond | 373↔387 | |||||
Sequence: CEFQCQPVSPTDYRC | ||||||
Disulfide bond | 389↔403 | |||||
Sequence: CAPGFAPKPDEPHKC | ||||||
Disulfide bond | 407↔416 | |||||
Sequence: CNETSCPADC | ||||||
Glycosylation | 408 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 412↔424 | |||||
Sequence: CPADCDPNSPTVC | ||||||
Disulfide bond | 426↔438 | |||||
Sequence: CPEGFILDEGSVC | ||||||
Disulfide bond | 444↔454 | |||||
Sequence: CSQGECFTSEC | ||||||
Disulfide bond | 449↔463 | |||||
Sequence: CFTSECRNFPGSYEC | ||||||
Disulfide bond | 465↔479 | |||||
Sequence: CGPDTALAGQISKDC | ||||||
Glycosylation | 494 | O-linked (Xyl...) (chondroitin sulfate) serine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Endothelial cells are unique in synthesizing thrombomodulin.
Gene expression databases
Interaction
Subunit
Interacts with ITGAL, ITGAM and ITGB2. Interacts with thrombin/F2; this interaction switches the specificity of thrombin from a procoagulant to an anticoagulant and antifibrinolytic protease. Interacts with ANGP1 and ANGP2; these interactions significantly inhibit the generation of activated PC and TAFIa/CPB2 by the thrombin/thrombomodulin complex. Interacts with PF4; this interaction enhances generation of activated protein C. Interacts with HMGB1; this interaction inhibits HMGB1 inflammatory activity.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 31-167 | C-type lectin | ||||
Sequence: VEHECFALFQGPATFLDASQACQRLQGHLMTVRSSVAADVISLLLSQSSMDLGPWIGLQLPQGCDDPVHLGPLRGFQWVTGDNHTSYSRWARPNDQTAPLCGPLCVTVSTATEAAPGEPAWEEKPCETETQGFLCEF | ||||||
Domain | 240-280 | EGF-like 1 | ||||
Sequence: GAWNCSVENGGCEYLCNRSTNEPRCLCPRDMDLQADGRSCA | ||||||
Domain | 283-323 | EGF-like 2 | ||||
Sequence: VVQSCNELCEHFCVSNAEVPGSYSCMCETGYQLAADGHRCE | ||||||
Domain | 324-362 | EGF-like 3; calcium-binding | ||||
Sequence: DVDDCKQGPNPCPQLCVNTKGGFECFCYDGYELVDGECV | ||||||
Domain | 364-404 | EGF-like 4 | ||||
Sequence: LLDPCFGSNCEFQCQPVSPTDYRCICAPGFAPKPDEPHKCE | ||||||
Domain | 403-439 | EGF-like 5 | ||||
Sequence: CEMFCNETSCPADCDPNSPTVCECPEGFILDEGSVCT | ||||||
Domain | 440-480 | EGF-like 6; calcium-binding | ||||
Sequence: DIDECSQGECFTSECRNFPGSYECICGPDTALAGQISKDCD | ||||||
Region | 476-513 | Disordered | ||||
Sequence: SKDCDPIPVREDTKEEEGSGEPPVSPTPGSPTGPPSAR | ||||||
Compositional bias | 480-494 | Basic and acidic residues | ||||
Sequence: DPIPVREDTKEEEGS |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length577
- Mass (Da)61,868
- Last updated1990-04-01 v1
- ChecksumB20E50B0FE745014
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 480-494 | Basic and acidic residues | ||||
Sequence: DPIPVREDTKEEEGS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X14432 EMBL· GenBank· DDBJ | CAA32597.1 EMBL· GenBank· DDBJ | mRNA | ||
BC019154 EMBL· GenBank· DDBJ | AAH19154.1 EMBL· GenBank· DDBJ | mRNA |