ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!
Search for

UniProtKB/Swiss-Prot entry P07204


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

Note: most headings are clickable, even if they don't appear as links. They link to the user manual or other documents.
Entry information
Entry name TRBM_HUMAN
Primary accession number P07204
Secondary accession numbers Q8IV29 Q9UC32
Integrated into Swiss-Prot on April 1, 1988
Sequence was last modified on February 1, 1991 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 126)
Name and origin of the protein
Protein name Thrombomodulin [Precursor]
Synonyms TM
Fetomodulin
CD141 antigen
Gene name
Name: THBD
Synonyms: THRM
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 19-43.
PubMed=2820710 [NCBI, ExPASy, EBI, Israel, Japan]
Suzuki K., Kusumoto H., Deyashiki Y., Nishioka J., Maruyama I., Zushi M., Kawahara S., Honda G., Yamamoto S., Horiguchi S.;
"Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation.";
EMBO J. 6:1891-1897(1987).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
DOI=10.1021/bi00388a025; PubMed=2822087 [NCBI, ExPASy, EBI, Israel, Japan]
Wen D., Dittman W.A., Ye R.D., Deaven L.L., Majerus P.W., Sadler J.E.;
"Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene.";
Biochemistry 26:4350-4357(1987).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2819876 [NCBI, ExPASy, EBI, Israel, Japan]
Jackman R.W., Beeler D.L., Fritze L., Soff G., Rosenberg R.D.;
"Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control.";
Proc. Natl. Acad. Sci. U.S.A. 84:6425-6429(1987).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2836377 [NCBI, ExPASy, EBI, Israel, Japan]
Shirai T., Shiojiri S., Ito H., Yamamoto S., Kusumoto H., Deyashiki Y., Maruyama I., Suzuki K.;
"Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C.";
J. Biochem. 103:281-285(1988).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-473.
SeattleSNPs program for genomic applications;
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/414865a; PubMed=11780052 [NCBI, ExPASy, EBI, Israel, Japan]
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 20.";
Nature 414:865-871(2001).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-473.
TISSUE=Brain, and Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
GLYCOSYLATION AT SER-492, AND MUTAGENESIS.
PubMed=8216207 [NCBI, ExPASy, EBI, Israel, Japan]
Gerlitz B., Hassell T., Vlahos C.J., Parkinson J.F., Bang N.U., Grinnell B.W.;
"Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine 474.";
Biochem. J. 295:131-140(1993).
[9]
HYDROXYLATION AT ASN-342.
PubMed=8390446 [NCBI, ExPASy, EBI, Israel, Japan]
Yamamoto S., Mizoguchi T., Tamaki T., Ohkuchi M., Kimura S., Aoki N.;
"Urinary thrombomodulin, its isolation and characterization.";
J. Biochem. 113:433-440(1993).
[10]
STRUCTURE BY NMR OF 389-407.
DOI=10.1074/jbc.270.40.23366; PubMed=7559494 [NCBI, ExPASy, EBI, Israel, Japan]
Adler M., Seto M.H., Nitecki D.E., Lin J.H., Light D.R., Morser J.;
"The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin.";
J. Biol. Chem. 270:23366-23372(1995).
[11]
STRUCTURE BY NMR OF 364-407.
PubMed=8528067 [NCBI, ExPASy, EBI, Israel, Japan]
Meininger D.P., Hunter M.J., Komives E.A.;
"Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin.";
Protein Sci. 4:1683-1695(1995).
[12]
STRUCTURE BY NMR OF 427-444.
DOI=10.1021/bi00250a007; PubMed=7947766 [NCBI, ExPASy, EBI, Israel, Japan]
Srinivasan J., Hu S., Hrabal R., Zhu Y., Komives E.A., Ni F.;
"Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects.";
Biochemistry 33:13553-13560(1994).
[13]
STRUCTURE BY NMR OF 427-444.
PubMed=8745396 [NCBI, ExPASy, EBI, Israel, Japan]
Hrabal R., Komives E.A., Ni F.;
"Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin.";
Protein Sci. 5:195-203(1996).
[14]
STRUCTURE BY NMR OF 405-444.
DOI=10.1006/jmbi.1997.1356; PubMed=9367781 [NCBI, ExPASy, EBI, Israel, Japan]
Sampoli Benitez B.A., Hunter M.J., Meininger D.P., Komives E.A.;
"Structure of the fifth EGF-like domain of thrombomodulin: an EGF-like domain with a novel disulfide-bonding pattern.";
J. Mol. Biol. 273:913-926(1997).
[15]
VARIANT TED TYR-486.
PubMed=7811989 [NCBI, ExPASy, EBI, Israel, Japan]
Oehlin A.-K., Marlar R.A.;
"The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease.";
Blood 85:330-336(1995).
[16]
VARIANT TED TYR-486, AND VARIANTS THR-43; ALA-79; SER-495 AND LEU-501.
PubMed=9198186 [NCBI, ExPASy, EBI, Israel, Japan]
Oehlin A.-K., Norlund L., Marlar R.A.;
"Thrombomodulin gene variations and thromboembolic disease.";
Thromb. Haemost. 78:396-400(1997).
[17]
VARIANT VAL-473.
PubMed=9157575 [NCBI, ExPASy, EBI, Israel, Japan]
Norlund L., Holm J., Zoller B., Oehlin A.-K.;
"A common thrombomodulin amino acid dimorphism is associated with myocardial infarction.";
Thromb. Haemost. 77:248-251(1997).
[18]
VARIANT THR-43.
PubMed=9843165 [NCBI, ExPASy, EBI, Israel, Japan]
Doggen C.J.M., Kunz G., Rosendaal F.R., Lane D.A., Vos H.L., Stubbs P.J., Manger Cats V., Ireland H.;
"A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men.";
Thromb. Haemost. 80:743-748(1998).
[19]
VARIANT VAL-473.
PubMed=11245641 [NCBI, ExPASy, EBI, Israel, Japan]
Wu K.K., Aleksic N., Ahn C., Boerwinkle E., Folsom A.R., Juneja H.;
"Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.";
Circulation 103:1386-1389(2001).
[20]
VARIANT TED TYR-486, AND VARIANT VAL-473.
DOI=10.1046/j.1365-2141.2002.03644.x; PubMed=12139752 [NCBI, ExPASy, EBI, Israel, Japan]
Faioni E.M., Franchi F., Castaman G., Biguzzi E., Rodeghiero F.;
"Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia.";
Br. J. Haematol. 118:595-599(2002).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X05495; CAA29045.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M16552; AAB59508.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J02973; AAA61175.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D00210; BAA00149.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF495471; AAM03232.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL049651; CAB51954.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC035602; AAH35602.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC053357; AAH53357.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A41442; THHUB.
RefSeq NP_000352.1; -.
UniGene Hs.2030
3D structure databases
PDB
1ADX; NMR; -; A=405-444.[ExPASy / RCSB / EBI]
1DQB; NMR; -; A=364-444.[ExPASy / RCSB / EBI]
1DX5; X-ray; 2.30 A; I/J/K/L=363-480.[ExPASy / RCSB / EBI]
1EGT; NMR; -; A=427-437.[ExPASy / RCSB / EBI]
1FGD; NMR; -; A=427-444.[ExPASy / RCSB / EBI]
1FGE; NMR; -; A=425-444.[ExPASy / RCSB / EBI]
1HLT; X-ray; 3.00 A; R=426-444.[ExPASy / RCSB / EBI]
1TMR; NMR; -; A=389-407.[ExPASy / RCSB / EBI]
1ZAQ; NMR; -; A=364-407.[ExPASy / RCSB / EBI]
2ADX; NMR; -; A=405-444.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1ADX; -.
1DQB; -.
1DX5; -.
1EGT; -.
1FGD; -.
1FGE; -.
1HLT; -.
1TMR; -.
1ZAQ; -.
2ADX; -.
ModBase P07204.
Protein-protein interaction databases
IntAct P07204; -.
PTM databases
GlycoSuiteDB P07204; -.
Enzyme and pathway databases
Reactome REACT_604; Hemostasis.
Organism-specific databases
H-InvDB HIX0015686; -.
HGNC HGNC:11784; THBD.
GenAtlas THBD.
HPA CAB002425; -.
HPA002982; -.
MIM 188040; gene+phenotype. [NCBI / EBI]
Orphanet 3324; Thrombomodulin anomalies, familial.
PharmGKB PA36496; -.
GeneCards P07204.
Gene expression databases
ArrayExpress P07204; -.
CleanEx HS_THBD; -.
GermOnline ENSG00000178726; Homo sapiens.
Ontologies
GO
GO:0005887; Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0005509; Molecular function: calcium ion binding (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004872; Molecular function: receptor activity (traceable author statement from ProtInc).
GO:0007596; Biological process: blood coagulation (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR001304; C-type_lectin.
IPR016186; C-type_lectin-like.
IPR016316; CD93/CD141.
IPR006210; EGF.
IPR000152; EGF-type_Asp/Asn_hydroxyl_CS.
IPR000742; EGF_3.
IPR001881; EGF_Ca_bd.
IPR013091; EGF_Ca_bd_2.
IPR006209; EGF_like.
IPR013032; EGF_like_reg_CS.
IPR001491; Thrombomodulin.
IPR015149; Tme5_EGF_like.
Graphical view of domain structure.
Gene3D G3DSA:3.10.100.10; C-type_lectin-like; 1.
Pfam PF00008; EGF; 2.
PF07645; EGF_CA; 2.
PF00059; Lectin_C; 1.
PF09064; Tme5_EGF_like; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF001775; CD93/CD141; 1.
PRINTS PR00907; THRMBOMODULN.
SMART SM00034; CLECT; 1.
SM00181; EGF; 5.
SM00179; EGF_CA; 1.
SMART graphical view of domain structure.
PROSITE PS00010; ASX_HYDROXYL; 2.
PS50041; C_TYPE_LECTIN_2; 1.
PS00022; EGF_1; FALSE_NEG.
PS01186; EGF_2; 2.
PS50026; EGF_3; 4.
PS01187; EGF_CA; 2.
PROSITE graphical view of domain structure (profiles).
BLOCKS P07204.
Genome annotation databases
Ensembl ENSG00000178726; Homo sapiens. [Contig view]
GeneID 7056; -.
KEGG hsa:7056; -.
NMPDR fig|9606.3.peg.19969; -.
Phylogenomic databases
HOGENOM P07204; -.
HOVERGEN P07204; -.
Other
DrugBank DB00055; Drotrecogin alfa.
LinkHub P07204; -.
SOURCE THBD; Homo sapiens.
ProtoNet P07204.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Blood coagulation; Direct protein sequencing; Disease mutation; EGF-like domain; Glycoprotein; Hydroxylation; Membrane; Polymorphism; Receptor; Repeat; Signal; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    18  18      
CHAIN   19   575  557     Thrombomodulin. PRO_0000007771
TOPO_DOM   19   515  497     Extracellular (Potential). 
TRANSMEM   516   539  24     Potential. 
TOPO_DOM   540   575  36     Cytoplasmic (Potential). 
DOMAIN   31   169  139     C-type lectin. 
DOMAIN   241   281  41     EGF-like 1. 
DOMAIN   284   324  41     EGF-like 2. 
DOMAIN   325   363  39     EGF-like 3; calcium-binding (Potential). 
DOMAIN   365   405  41     EGF-like 4. 
DOMAIN   404   440  37     EGF-like 5. 
DOMAIN   441   481  41     EGF-like 6; calcium-binding (Potential). 
MOD_RES   342   342        3-hydroxyasparagine. 
CARBOHYD   47    47        N-linked (GlcNAc...) (Potential). 
CARBOHYD   115   115        N-linked (GlcNAc...) (Potential). 
CARBOHYD   116   116        N-linked (GlcNAc...) (Potential). 
CARBOHYD   382   382        N-linked (GlcNAc...) (Potential). 
CARBOHYD   409   409        N-linked (GlcNAc...) (Potential). 
CARBOHYD   490   490        O-linked (Xyl...) (chondroitin sulfate). 
CARBOHYD   492   492        O-linked (Xyl...) (chondroitin sulfate). 
DISULFID   137   158        By similarity. 
DISULFID   245   256        By similarity. 
DISULFID   252   265        By similarity. 
DISULFID   267   280        By similarity. 
DISULFID   288   296        By similarity. 
DISULFID   292   308        By similarity. 
DISULFID   310   323        By similarity. 
DISULFID   329   340        By similarity. 
DISULFID   336   349        By similarity. 
DISULFID   351   362        By similarity. 
DISULFID   369   378        By similarity. 
DISULFID   374   388        By similarity. 
DISULFID   390   404         
DISULFID   408   413         
DISULFID   417   425         
DISULFID   427   439         
DISULFID   445   455        By similarity. 
DISULFID   451   464        By similarity. 
DISULFID   466   480        By similarity. 
VARIANT   43    43  1     A -> T (in dbSNP:rs1800576 [NCBI]). VAR_011368 
VARIANT   79    79  1     G -> A (in dbSNP:rs1800577 [NCBI]). VAR_011369 
VARIANT   473   473  1     A -> V (in dbSNP:rs1042579 [NCBI]). VAR_011370 [3D]
VARIANT   486   486  1     D -> Y (in TED). VAR_011371 
VARIANT   495   495  1     P -> S (in dbSNP:rs1800578 [NCBI]). VAR_011372 
VARIANT   501   501  1     P -> L (in dbSNP:rs1800579 [NCBI]). VAR_011373 
HELIX   368   371  4      
STRAND   375   380  6      
STRAND   386   389  4      
STRAND   394   397  4      
STRAND   400   406  7      
STRAND   410   414  5      
STRAND   431   434  4      
TURN   435   437  3      
STRAND   438   441  4      
HELIX   444   447  4      
STRAND   454   457  4      
STRAND   459   466  8      
STRAND   473   477  5      
Sequence information
Length: 575 AA [This is the length of the unprocessed precursor] Molecular weight: 60329 Da [This is the MW of the unprocessed precursor] CRC64: 9AF03CD151227D52 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MLGVLVLGAL ALAGLGFPAP AEPQPGGSQC VEHDCFALYP GPATFLNASQ ICDGLRGHLM 

        70         80         90        100        110        120 
TVRSSVAADV ISLLLNGDGG VGRRRLWIGL QLPPGCGDPK RLGPLRGFQW VTGDNNTSYS 

       130        140        150        160        170        180 
RWARLDLNGA PLCGPLCVAV SAAEATVPSE PIWEEQQCEV KADGFLCEFH FPATCRPLAV 

       190        200        210        220        230        240 
EPGAAAAAVS ITYGTPFAAR GADFQALPVG SSAAVAPLGL QLMCTAPPGA VQGHWAREAP 

       250        260        270        280        290        300 
GAWDCSVENG GCEHACNAIP GAPRCQCPAG AALQADGRSC TASATQSCND LCEHFCVPNP 

       310        320        330        340        350        360 
DQPGSYSCMC ETGYRLAADQ HRCEDVDDCI LEPSPCPQRC VNTQGGFECH CYPNYDLVDG 

       370        380        390        400        410        420 
ECVEPVDPCF RANCEYQCQP LNQTSYLCVC AEGFAPIPHE PHRCQMFCNQ TACPADCDPN 

       430        440        450        460        470        480 
TQASCECPEG YILDDGFICT DIDECENGGF CSGVCHNLPG TFECICGPDS ALARHIGTDC 

       490        500        510        520        530        540 
DSGKVDGGDS GSGEPPPSPT PGSTLTPPAV GL