Human Gene THBD (uc002wss.3)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:23,026,270-23,030,301)mRNA (may differ from genome)Protein (575 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): THBD
CDC HuGE Published Literature: THBD
Positive Disease Associations: acute myocardial infarction , atherosclerosis, coronary , cerebral infarct , myocardial infarction , Osteoporosis , stroke; atherosclerosis , thrombosis, deep vein
Related Studies:
  1. 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.
  2. 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.
  3. 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.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: THBD
Diseases sorted by gene-association score: thrombophilia due to thrombomodulin defect* (1679), hemolytic uremic syndrome, atypical 6* (1256), thbd-related atypical hemolytic-uremic syndrome* (100), hemolytic uremic syndrome, atypical 1* (47), thrombophilia (29), thrombosis (28), dengue shock syndrome (27), sarcomatoid mesothelioma (23), peritoneal mesothelioma (23), eisenmenger syndrome (23), lymphohistiocytoid mesothelioma (22), malignant biphasic mesothelioma (22), hemolytic-uremic syndrome (19), disseminated intravascular coagulation (19), unilateral absence of a pulmonary artery (18), erythromelalgia (18), hepatic veno-occlusive disease (14), benign mesothelioma (13), protein c deficiency (13), malignant pleural mesothelioma (13), thrombotic thrombocytopenic purpura (12), mesothelioma, somatic (12), collagen disease (12), churg-strauss syndrome (12), adenomatoid tumor (11), legg-calve-perthes disease (11), acute respiratory distress syndrome (10), spotted fever (10), head injury (9), miller syndrome (9), eclampsia (9), peripheral vascular disease (9), malignant epithelial mesothelioma (9), essential thrombocythemia (9), antiphospholipid syndrome (8), pulmonary hypertension (8), placental abruption (8), mercury poisoning (8), hyperhomocysteinemia (8), vasculitis (7), thrombotic thrombocytopenic purpura, acquired (7), carotid artery occlusion (7), boutonneuse fever (7), ovarian brenner tumor (7), atherosclerosis (7), thrombophilia due to activated protein c resistance (7), takayasu arteritis (6), thrombophilia due to thrombin defect (6), carotid artery disease (6), hemorrhagic disease (6), purpura (6), diabetic angiopathy (6), senile angioma (6), rete testis adenocarcinoma (6), chronic active epstein-barr virus infection (5), stroke, ischemic (5), pericardium cancer (5), marantic endocarditis (5), thrombocytopenia (5), rete testis neoplasm (5), pericardial mesothelioma (5), granulomatous angiitis (5), lung sarcoma (5), blood coagulation disease (5), desmoplastic small round cell tumor (5), dysfibrinogenemia (5), shwartzman phenomenon (5), cystitis cystica (4), systemic lupus erythematosus (4), vascular disease (4), myocardial infarction (4), meningococcemia (4), transverse colon cancer (3), hellp syndrome (2), arteriosclerosis (2), leukemia, acute promyelocytic, somatic (2), polycythemia vera, somatic (2), malaria (2), behcet syndrome (2), diabetes mellitus, insulin-dependent (1), preeclampsia/eclampsia 1 (1), hypertension, essential (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 49.90 RPKM in Skin - Not Sun Exposed (Suprapubic)
Total median expression: 645.11 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -80.30160-0.502 Picture PostScript Text
3' UTR -619.122144-0.289 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001304 - C-type_lectin
IPR016186 - C-type_lectin-like
IPR016187 - C-type_lectin_fold
IPR016316 - CD93/CD141
IPR000742 - EG-like_dom
IPR001881 - EGF-like_Ca-bd
IPR013032 - EGF-like_CS
IPR000152 - EGF-type_Asp/Asn_hydroxyl_site
IPR018097 - EGF_Ca-bd_CS
IPR001491 - Thrombomodulin
IPR015149 - Tme5_EGF-like

Pfam Domains:
PF00059 - Lectin C-type domain
PF07645 - Calcium-binding EGF domain
PF09064 - Thrombomodulin like fifth domain, EGF-like
PF12662 - Complement Clr-like EGF-like
PF14670 - Coagulation Factor Xa inhibitory site

SCOP Domains:
56436 - C-type lectin-like
57567 - Serine proterase inhibitors
57196 - EGF/Laminin
57184 - Growth factor receptor domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1ADX - NMR MuPIT 1DQB - NMR MuPIT 1DX5 - X-ray MuPIT 1EGT - NMR 1FGD - NMR MuPIT 1FGE - NMR MuPIT 1HLT - X-ray MuPIT 1TMR - NMR MuPIT 1ZAQ - NMR MuPIT 2ADX - NMR MuPIT 3GIS - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P07204
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004888 transmembrane signaling receptor activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0038023 signaling receptor activity

Biological Process:
GO:0007165 signal transduction
GO:0007565 female pregnancy
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0010165 response to X-ray
GO:0010544 negative regulation of platelet activation
GO:0030195 negative regulation of blood coagulation
GO:0032496 response to lipopolysaccharide
GO:0051591 response to cAMP
GO:0051918 negative regulation of fibrinolysis

Cellular Component:
GO:0005615 extracellular space
GO:0005774 vacuolar membrane
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016327 apicolateral plasma membrane


-  Descriptions from all associated GenBank mRNAs
  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

-  Other Names for This Gene
  Alternate Gene Symbols: NM_000361, NP_000352, P07204, Q8IV29, Q9UC32, THRM, TRBM_HUMAN
UCSC ID: uc002wss.3
RefSeq Accession: NM_000361
Protein: P07204 (aka TRBM_HUMAN)
CCDS: CCDS13148.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene THBD:
husa (Genetic Atypical Hemolytic-Uremic Syndrome)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000361.2
exon count: 1CDS single in 3' UTR: no RNA size: 4048
ORF size: 1728CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3641.00frame shift in genome: no % Coverage: 99.60
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.