Description: Homo sapiens thrombomodulin (THBD), mRNA. RefSeq Summary (NM_000361): The protein encoded by this intronless gene is an endothelial-specific type I membrane receptor that binds thrombin. This binding results in the activation of protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. Mutations in this gene are a cause of thromboembolic disease, also known as inherited thrombophilia. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr20:23,026,270-23,030,301 Size: 4,032 Total Exon Count: 1 Strand: - Coding Region Position: hg19 chr20:23,028,414-23,030,141 Size: 1,728 Coding Exon Count: 1
ID:TRBM_HUMAN DESCRIPTION: RecName: Full=Thrombomodulin; Short=TM; AltName: Full=Fetomodulin; AltName: CD_antigen=CD141; Flags: Precursor; FUNCTION: Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated. INTERACTION: P00734:F2; NbExp=4; IntAct=EBI-941422, EBI-297094; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Endothelial cells are unique in synthesizing thrombomodulin. PTM: N-glycosylated. PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. DISEASE: Defects in THBD are the cause of thrombophilia due to thrombomodulin defect (THPH12) [MIM:614486]. A hemostatic disorder characterized by a tendency to thrombosis. DISEASE: Defects in THBD are a cause of susceptibility to hemolytic uremic syndrome atypical type 6 (AHUS6) [MIM:612926]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. SIMILARITY: Contains 1 C-type lectin domain. SIMILARITY: Contains 6 EGF-like domains. WEB RESOURCE: Name=Wikipedia; Note=Thrombomodulin entry; URL="http://en.wikipedia.org/wiki/Thrombomodulin"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/thbd/"; WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; Note=Thrombomodulin; URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_211";
acute myocardial infarction Ranjith N 2003, Haemostatic gene polymorphisms in young indian asian subjects with acute myocardial infarction., Medical science monitor. 2003 Oct;9(10):CR417-21.
[PubMed 14523329]
The Leiden Factor V and prothrombin 20210 GgA polymorphisms have no value in disease association studies in the Indian Asian population. In smokers, the thrombomodulin Ala455Val variant allele emerges as a significant risk factor for coronary heart disease.
atherosclerosis, coronary Konstantoulas, C. J. et al. 2004, A combination of two common thrombomodulin gene variants (-1208-1209TTdelTT and A455V) influence risk of coronary heart disease: a prospective studyin men., Atherosclerosis. 2004 Nov;177(1):97-104.
[PubMed 15488871]
Overall, these findings may suggest that the common TM allele confers protection against the adverse CHD effect of either plasma triglyceride-containing lipoproteins, or the underlying atherosclerotic mechanism of the metabolic syndrome, and that this process is defective in carriers of V/delTT.
cerebral infarct Cole, J. W. et al. 2004, Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population:the Stroke Prevention in Young Women Study., BMC neurology [electronic resource]. 2004 Dec;4(1):21.
[PubMed 15574195]
Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P07204
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF205936 - JP 2014500723-A/13439: Polycomb-Associated Non-Coding RNAs. AK091934 - Homo sapiens cDNA FLJ34615 fis, clone KIDNE2014290, highly similar to THROMBOMODULIN PRECURSOR. AX747264 - Sequence 789 from Patent EP1308459. M16552 - Human endothelial cell thrombomodulin mRNA, complete cds. BC035602 - Homo sapiens thrombomodulin, mRNA (cDNA clone MGC:45302 IMAGE:5176531), complete cds. AK123557 - Homo sapiens cDNA FLJ41563 fis, clone CTONG1000341, highly similar to THROMBOMODULIN PRECURSOR. JD347408 - Sequence 328432 from Patent EP1572962. LF349943 - JP 2014500723-A/157446: Polycomb-Associated Non-Coding RNAs. X05495 - Human mRNA for thrombomodulin precursor. JD097295 - Sequence 78319 from Patent EP1572962. JD417841 - Sequence 398865 from Patent EP1572962. JD371621 - Sequence 352645 from Patent EP1572962. JD424416 - Sequence 405440 from Patent EP1572962. JD564668 - Sequence 545692 from Patent EP1572962. JD535915 - Sequence 516939 from Patent EP1572962. LF349944 - JP 2014500723-A/157447: Polycomb-Associated Non-Coding RNAs. JD130791 - Sequence 111815 from Patent EP1572962. JD171607 - Sequence 152631 from Patent EP1572962. JD279476 - Sequence 260500 from Patent EP1572962. JD119666 - Sequence 100690 from Patent EP1572962. JD122790 - Sequence 103814 from Patent EP1572962. JD287673 - Sequence 268697 from Patent EP1572962. LF349945 - JP 2014500723-A/157448: Polycomb-Associated Non-Coding RNAs. JD427136 - Sequence 408160 from Patent EP1572962. JD038727 - Sequence 19751 from Patent EP1572962. LF349946 - JP 2014500723-A/157449: Polycomb-Associated Non-Coding RNAs. LF349947 - JP 2014500723-A/157450: Polycomb-Associated Non-Coding RNAs. JD315192 - Sequence 296216 from Patent EP1572962. LF349948 - JP 2014500723-A/157451: Polycomb-Associated Non-Coding RNAs. BC053357 - Homo sapiens thrombomodulin, mRNA (cDNA clone MGC:61509 IMAGE:6007870), complete cds. JD126418 - Sequence 107442 from Patent EP1572962. JD290142 - Sequence 271166 from Patent EP1572962. JD261305 - Sequence 242329 from Patent EP1572962. JD301263 - Sequence 282287 from Patent EP1572962. LF349950 - JP 2014500723-A/157453: Polycomb-Associated Non-Coding RNAs. JD528860 - Sequence 509884 from Patent EP1572962. JD477224 - Sequence 458248 from Patent EP1572962. JD289794 - Sequence 270818 from Patent EP1572962. LF349953 - JP 2014500723-A/157456: Polycomb-Associated Non-Coding RNAs. LF211857 - JP 2014500723-A/19360: Polycomb-Associated Non-Coding RNAs. E09543 - cDNA encoding fragment of human glycopeptide which promote protein C activation by thrombin. AB587391 - Synthetic construct DNA, clone: pF1KB5605, Homo sapiens THBD gene for thrombomodulin, without stop codon, in Flexi system. LF212935 - JP 2014500723-A/20438: Polycomb-Associated Non-Coding RNAs. E38846 - Process for producing soluble thrombomodulin with high purity. E38847 - Process for producing soluble thrombomodulin with high purity. E09580 - cDNA encoding thrombomodulin(r-GAG-UTM). LF349956 - JP 2014500723-A/157459: Polycomb-Associated Non-Coding RNAs. E38844 - Process for producing soluble thrombomodulin with high purity. E38845 - Process for producing soluble thrombomodulin with high purity. LF349957 - JP 2014500723-A/157460: Polycomb-Associated Non-Coding RNAs. LF349958 - JP 2014500723-A/157461: Polycomb-Associated Non-Coding RNAs. LF349959 - JP 2014500723-A/157462: Polycomb-Associated Non-Coding RNAs. LF349960 - JP 2014500723-A/157463: Polycomb-Associated Non-Coding RNAs. LF349961 - JP 2014500723-A/157464: Polycomb-Associated Non-Coding RNAs. LF349962 - JP 2014500723-A/157465: Polycomb-Associated Non-Coding RNAs. LF349963 - JP 2014500723-A/157466: Polycomb-Associated Non-Coding RNAs. JD125420 - Sequence 106444 from Patent EP1572962. JD124985 - Sequence 106009 from Patent EP1572962. JD143284 - Sequence 124308 from Patent EP1572962. JD351916 - Sequence 332940 from Patent EP1572962. JD494108 - Sequence 475132 from Patent EP1572962. MA585520 - JP 2018138019-A/157446: Polycomb-Associated Non-Coding RNAs. MA585521 - JP 2018138019-A/157447: Polycomb-Associated Non-Coding RNAs. MA585522 - JP 2018138019-A/157448: Polycomb-Associated Non-Coding RNAs. MA585523 - JP 2018138019-A/157449: Polycomb-Associated Non-Coding RNAs. MA585524 - JP 2018138019-A/157450: Polycomb-Associated Non-Coding RNAs. MA585525 - JP 2018138019-A/157451: Polycomb-Associated Non-Coding RNAs. MA585527 - JP 2018138019-A/157453: Polycomb-Associated Non-Coding RNAs. MA585530 - JP 2018138019-A/157456: Polycomb-Associated Non-Coding RNAs. MA585533 - JP 2018138019-A/157459: Polycomb-Associated Non-Coding RNAs. MA585534 - JP 2018138019-A/157460: Polycomb-Associated Non-Coding RNAs. MA585535 - JP 2018138019-A/157461: Polycomb-Associated Non-Coding RNAs. MA585536 - JP 2018138019-A/157462: Polycomb-Associated Non-Coding RNAs. MA585537 - JP 2018138019-A/157463: Polycomb-Associated Non-Coding RNAs. MA585538 - JP 2018138019-A/157464: Polycomb-Associated Non-Coding RNAs. MA585539 - JP 2018138019-A/157465: Polycomb-Associated Non-Coding RNAs. MA585540 - JP 2018138019-A/157466: Polycomb-Associated Non-Coding RNAs. MA441513 - JP 2018138019-A/13439: Polycomb-Associated Non-Coding RNAs. MA447434 - JP 2018138019-A/19360: Polycomb-Associated Non-Coding RNAs. MA448512 - JP 2018138019-A/20438: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04610 - Complement and coagulation cascades
Reactome (by CSHL, EBI, and GO)
Protein P07204 (Reactome details) participates in the following event(s):
R-HSA-141046 activated thrombin (factor IIa) + thrombomodulin -> activated thrombin:thrombomodulin R-HSA-141040 Activated thrombin:thrombomodulin cleaves PROCR:Protein C to PROCR:Activated protein C R-HSA-140875 Common Pathway of Fibrin Clot Formation R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade) R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-109582 Hemostasis