GenomeNet

Database: UniProt
Entry: P07204
LinkDB: P07204
Original site: P07204 
ID   TRBM_HUMAN              Reviewed;         575 AA.
AC   P07204; Q8IV29; Q9UC32;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 2.
DT   13-FEB-2019, entry version 228.
DE   RecName: Full=Thrombomodulin;
DE            Short=TM;
DE   AltName: Full=Fetomodulin;
DE   AltName: CD_antigen=CD141;
DE   Flags: Precursor;
GN   Name=THBD; Synonyms=THRM;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 19-43.
RX   PubMed=2820710;
RA   Suzuki K., Kusumoto H., Deyashiki Y., Nishioka J., Maruyama I.,
RA   Zushi M., Kawahara S., Honda G., Yamamoto S., Horiguchi S.;
RT   "Structure and expression of human thrombomodulin, a thrombin receptor
RT   on endothelium acting as a cofactor for protein C activation.";
RL   EMBO J. 6:1891-1897(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX   PubMed=2822087; DOI=10.1021/bi00388a025;
RA   Wen D., Dittman W.A., Ye R.D., Deaven L.L., Majerus P.W., Sadler J.E.;
RT   "Human thrombomodulin: complete cDNA sequence and chromosome
RT   localization of the gene.";
RL   Biochemistry 26:4350-4357(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2819876; DOI=10.1073/pnas.84.18.6425;
RA   Jackman R.W., Beeler D.L., Fritze L., Soff G., Rosenberg R.D.;
RT   "Human thrombomodulin gene is intron depleted: nucleic acid sequences
RT   of the cDNA and gene predict protein structure and suggest sites of
RT   regulatory control.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:6425-6429(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2836377;
RA   Shirai T., Shiojiri S., Ito H., Yamamoto S., Kusumoto H.,
RA   Deyashiki Y., Maruyama I., Suzuki K.;
RT   "Gene structure of human thrombomodulin, a cofactor for thrombin-
RT   catalyzed activation of protein C.";
RL   J. Biochem. 103:281-285(1988).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-473.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-473.
RC   TISSUE=Brain, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   GLYCOSYLATION AT SER-492, AND MUTAGENESIS.
RX   PubMed=8216207; DOI=10.1042/bj2950131;
RA   Gerlitz B., Hassell T., Vlahos C.J., Parkinson J.F., Bang N.U.,
RA   Grinnell B.W.;
RT   "Identification of the predominant glycosaminoglycan-attachment site
RT   in soluble recombinant human thrombomodulin: potential regulation of
RT   functionality by glycosyltransferase competition for serine 474.";
RL   Biochem. J. 295:131-140(1993).
RN   [9]
RP   HYDROXYLATION AT ASN-342.
RX   PubMed=8390446;
RA   Yamamoto S., Mizoguchi T., Tamaki T., Ohkuchi M., Kimura S., Aoki N.;
RT   "Urinary thrombomodulin, its isolation and characterization.";
RL   J. Biochem. 113:433-440(1993).
RN   [10]
RP   INTERACTION WITH ITGAL; ITGAM AND ITGB2, AND DOMAIN.
RX   PubMed=27055590; DOI=10.1016/j.bbrc.2016.04.007;
RA   Kawamoto E., Okamoto T., Takagi Y., Honda G., Suzuki K., Imai H.,
RA   Shimaoka M.;
RT   "LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of
RT   thrombomodulin.";
RL   Biochem. Biophys. Res. Commun. 473:1005-1012(2016).
RN   [11]
RP   STRUCTURE BY NMR OF 389-407.
RX   PubMed=7559494; DOI=10.1074/jbc.270.40.23366;
RA   Adler M., Seto M.H., Nitecki D.E., Lin J.H., Light D.R., Morser J.;
RT   "The structure of a 19-residue fragment from the C-loop of the fourth
RT   epidermal growth factor-like domain of thrombomodulin.";
RL   J. Biol. Chem. 270:23366-23372(1995).
RN   [12]
RP   STRUCTURE BY NMR OF 364-407.
RX   PubMed=8528067; DOI=10.1002/pro.5560040904;
RA   Meininger D.P., Hunter M.J., Komives E.A.;
RT   "Synthesis, activity, and preliminary structure of the fourth EGF-like
RT   domain of thrombomodulin.";
RL   Protein Sci. 4:1683-1695(1995).
RN   [13]
RP   STRUCTURE BY NMR OF 427-444.
RX   PubMed=7947766; DOI=10.1021/bi00250a007;
RA   Srinivasan J., Hu S., Hrabal R., Zhu Y., Komives E.A., Ni F.;
RT   "Thrombin-bound structure of an EGF subdomain from human
RT   thrombomodulin determined by transferred nuclear Overhauser effects.";
RL   Biochemistry 33:13553-13560(1994).
RN   [14]
RP   STRUCTURE BY NMR OF 427-444.
RX   PubMed=8745396; DOI=10.1002/pro.5560050202;
RA   Hrabal R., Komives E.A., Ni F.;
RT   "Structural resiliency of an EGF-like subdomain bound to its target
RT   protein, thrombin.";
RL   Protein Sci. 5:195-203(1996).
RN   [15]
RP   STRUCTURE BY NMR OF 405-444.
RX   PubMed=9367781; DOI=10.1006/jmbi.1997.1356;
RA   Sampoli Benitez B.A., Hunter M.J., Meininger D.P., Komives E.A.;
RT   "Structure of the fifth EGF-like domain of thrombomodulin: an EGF-like
RT   domain with a novel disulfide-bonding pattern.";
RL   J. Mol. Biol. 273:913-926(1997).
RN   [16]
RP   VARIANT THPH12 TYR-486.
RX   PubMed=7811989;
RA   Oehlin A.-K., Marlar R.A.;
RT   "The first mutation identified in the thrombomodulin gene in a 45-
RT   year-old man presenting with thromboembolic disease.";
RL   Blood 85:330-336(1995).
RN   [17]
RP   VARIANT THPH12 TYR-486, AND VARIANTS THR-43; ALA-79; SER-495 AND
RP   LEU-501.
RX   PubMed=9198186;
RA   Oehlin A.-K., Norlund L., Marlar R.A.;
RT   "Thrombomodulin gene variations and thromboembolic disease.";
RL   Thromb. Haemost. 78:396-400(1997).
RN   [18]
RP   VARIANT VAL-473.
RX   PubMed=9157575;
RA   Norlund L., Holm J., Zoller B., Oehlin A.-K.;
RT   "A common thrombomodulin amino acid dimorphism is associated with
RT   myocardial infarction.";
RL   Thromb. Haemost. 77:248-251(1997).
RN   [19]
RP   VARIANT THR-43.
RX   PubMed=9843165;
RA   Doggen C.J.M., Kunz G., Rosendaal F.R., Lane D.A., Vos H.L.,
RA   Stubbs P.J., Manger Cats V., Ireland H.;
RT   "A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr,
RT   and the risk of myocardial infarction in men.";
RL   Thromb. Haemost. 80:743-748(1998).
RN   [20]
RP   VARIANT VAL-473.
RX   PubMed=11245641; DOI=10.1161/01.CIR.103.10.1386;
RA   Wu K.K., Aleksic N., Ahn C., Boerwinkle E., Folsom A.R., Juneja H.;
RT   "Thrombomodulin Ala455Val polymorphism and risk of coronary heart
RT   disease.";
RL   Circulation 103:1386-1389(2001).
RN   [21]
RP   VARIANT THPH12 TYR-486, AND VARIANT VAL-473.
RX   PubMed=12139752; DOI=10.1046/j.1365-2141.2002.03644.x;
RA   Faioni E.M., Franchi F., Castaman G., Biguzzi E., Rodeghiero F.;
RT   "Mutations in the thrombomodulin gene are rare in patients with severe
RT   thrombophilia.";
RL   Br. J. Haematol. 118:595-599(2002).
RN   [22]
RP   VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486; SER-495 AND LEU-501,
RP   CHARACTERIZATION OF VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486;
RP   SER-495 AND LEU-501, AND VARIANT VAL-473.
RX   PubMed=19625716; DOI=10.1056/NEJMoa0810739;
RA   Delvaeye M., Noris M., De Vriese A., Esmon C.T., Esmon N.L.,
RA   Ferrell G., Del-Favero J., Plaisance S., Claes B., Lambrechts D.,
RA   Zoja C., Remuzzi G., Conway E.M.;
RT   "Thrombomodulin mutations in atypical hemolytic-uremic syndrome.";
RL   N. Engl. J. Med. 361:345-357(2009).
RN   [23]
RP   VARIANTS AHUS6 GLU-34 AND GLY-236.
RX   PubMed=20513133; DOI=10.1002/humu.21256;
RA   Maga T.K., Nishimura C.J., Weaver A.E., Frees K.L., Smith R.J.H.;
RT   "Mutations in alternative pathway complement proteins in American
RT   patients with atypical hemolytic uremic syndrome.";
RL   Hum. Mutat. 31:E1445-E1460(2010).
CC   -!- FUNCTION: Thrombomodulin is a specific endothelial cell receptor
CC       that forms a 1:1 stoichiometric complex with thrombin. This
CC       complex is responsible for the conversion of protein C to the
CC       activated protein C (protein Ca). Once evolved, protein Ca
CC       scissions the activated cofactors of the coagulation mechanism,
CC       factor Va and factor VIIIa, and thereby reduces the amount of
CC       thrombin generated.
CC   -!- SUBUNIT: Interacts with ITGAL, ITGAM and ITGB2.
CC       {ECO:0000269|PubMed:27055590}.
CC   -!- INTERACTION:
CC       P00734:F2; NbExp=4; IntAct=EBI-941422, EBI-297094;
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC       protein.
CC   -!- TISSUE SPECIFICITY: Endothelial cells are unique in synthesizing
CC       thrombomodulin.
CC   -!- DOMAIN: Extracellular region (481-515) contains a binding side for
CC       alpha-L/beta-2 and alpha-M/beta-2 integrin.
CC       {ECO:0000269|PubMed:27055590}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:8216207}.
CC   -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC       aspartate and asparagine is (R) stereospecific within EGF domains.
CC       {ECO:0000269|PubMed:8390446}.
CC   -!- DISEASE: Thrombophilia due to thrombomodulin defect (THPH12)
CC       [MIM:614486]: A hemostatic disorder characterized by a tendency to
CC       thrombosis. {ECO:0000269|PubMed:12139752,
CC       ECO:0000269|PubMed:7811989, ECO:0000269|PubMed:9198186}. Note=The
CC       disease may be caused by mutations affecting the gene represented
CC       in this entry. The role of thrombomodulin in thrombosis is
CC       controversial. It is likely that genetic or environmental risk
CC       factors in addition to THBD variation are involved in the
CC       pathogenesis of venous thrombosis.
CC   -!- DISEASE: Hemolytic uremic syndrome atypical 6 (AHUS6)
CC       [MIM:612926]: An atypical form of hemolytic uremic syndrome. It is
CC       a complex genetic disease characterized by microangiopathic
CC       hemolytic anemia, thrombocytopenia, renal failure and absence of
CC       episodes of enterocolitis and diarrhea. In contrast to typical
CC       hemolytic uremic syndrome, atypical forms have a poorer prognosis,
CC       with higher death rates and frequent progression to end-stage
CC       renal disease. {ECO:0000269|PubMed:19625716,
CC       ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry. Other genes may play a role in modifying the phenotype.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Thrombomodulin entry;
CC       URL="https://en.wikipedia.org/wiki/Thrombomodulin";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/thbd/";
CC   -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC       Note=Thrombomodulin;
CC       URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_211";
DR   EMBL; X05495; CAA29045.1; -; mRNA.
DR   EMBL; M16552; AAB59508.1; -; mRNA.
DR   EMBL; J02973; AAA61175.1; -; Genomic_DNA.
DR   EMBL; D00210; BAA00149.1; -; Genomic_DNA.
DR   EMBL; AF495471; AAM03232.1; -; Genomic_DNA.
DR   EMBL; AL049651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC035602; AAH35602.2; -; mRNA.
DR   EMBL; BC053357; AAH53357.1; -; mRNA.
DR   CCDS; CCDS13148.1; -.
DR   PIR; A41442; THHUB.
DR   RefSeq; NP_000352.1; NM_000361.2.
DR   UniGene; Hs.2030; -.
DR   PDB; 1ADX; NMR; -; A=405-444.
DR   PDB; 1DQB; NMR; -; A=364-444.
DR   PDB; 1DX5; X-ray; 2.30 A; I/J/K/L=363-480.
DR   PDB; 1EGT; NMR; -; A=427-444.
DR   PDB; 1FGD; NMR; -; A=427-444.
DR   PDB; 1FGE; NMR; -; A=425-444.
DR   PDB; 1HLT; X-ray; 3.00 A; R=426-444.
DR   PDB; 1TMR; NMR; -; A=389-405.
DR   PDB; 1ZAQ; NMR; -; A=364-407.
DR   PDB; 2ADX; NMR; -; A=405-444.
DR   PDB; 3GIS; X-ray; 2.40 A; X/Y/Z=363-483.
DR   PDB; 5TO3; X-ray; 2.34 A; B=363-483.
DR   PDBsum; 1ADX; -.
DR   PDBsum; 1DQB; -.
DR   PDBsum; 1DX5; -.
DR   PDBsum; 1EGT; -.
DR   PDBsum; 1FGD; -.
DR   PDBsum; 1FGE; -.
DR   PDBsum; 1HLT; -.
DR   PDBsum; 1TMR; -.
DR   PDBsum; 1ZAQ; -.
DR   PDBsum; 2ADX; -.
DR   PDBsum; 3GIS; -.
DR   PDBsum; 5TO3; -.
DR   ProteinModelPortal; P07204; -.
DR   SMR; P07204; -.
DR   BioGrid; 112914; 5.
DR   IntAct; P07204; 25.
DR   STRING; 9606.ENSP00000366307; -.
DR   DrugBank; DB00055; Drotrecogin alfa.
DR   DrugBank; DB01050; Ibuprofen.
DR   GlyConnect; 591; -.
DR   iPTMnet; P07204; -.
DR   PhosphoSitePlus; P07204; -.
DR   SwissPalm; P07204; -.
DR   UniCarbKB; P07204; -.
DR   BioMuta; THBD; -.
DR   DMDM; 136170; -.
DR   EPD; P07204; -.
DR   jPOST; P07204; -.
DR   MaxQB; P07204; -.
DR   PaxDb; P07204; -.
DR   PeptideAtlas; P07204; -.
DR   PRIDE; P07204; -.
DR   ProteomicsDB; 51973; -.
DR   DNASU; 7056; -.
DR   Ensembl; ENST00000377103; ENSP00000366307; ENSG00000178726.
DR   GeneID; 7056; -.
DR   KEGG; hsa:7056; -.
DR   UCSC; uc002wss.4; human.
DR   CTD; 7056; -.
DR   DisGeNET; 7056; -.
DR   EuPathDB; HostDB:ENSG00000178726.6; -.
DR   GeneCards; THBD; -.
DR   GeneReviews; THBD; -.
DR   H-InvDB; HIX0174703; -.
DR   HGNC; HGNC:11784; THBD.
DR   HPA; CAB002425; -.
DR   HPA; HPA002982; -.
DR   MalaCards; THBD; -.
DR   MIM; 188040; gene.
DR   MIM; 612926; phenotype.
DR   MIM; 614486; phenotype.
DR   neXtProt; NX_P07204; -.
DR   OpenTargets; ENSG00000178726; -.
DR   Orphanet; 217023; Atypical hemolytic-uremic syndrome with thrombomodulin anomaly.
DR   Orphanet; 436169; Thrombomodulin-related bleeding disorder.
DR   PharmGKB; PA36496; -.
DR   eggNOG; ENOG410IF0T; Eukaryota.
DR   eggNOG; ENOG410Y5JS; LUCA.
DR   GeneTree; ENSGT00940000163276; -.
DR   HOGENOM; HOG000114624; -.
DR   HOVERGEN; HBG000291; -.
DR   InParanoid; P07204; -.
DR   KO; K03907; -.
DR   OMA; LCGPLCV; -.
DR   OrthoDB; 1174178at2759; -.
DR   PhylomeDB; P07204; -.
DR   TreeFam; TF330714; -.
DR   Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR   Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR   SIGNOR; P07204; -.
DR   ChiTaRS; THBD; human.
DR   EvolutionaryTrace; P07204; -.
DR   GeneWiki; Thrombomodulin; -.
DR   GenomeRNAi; 7056; -.
DR   PRO; PR:P07204; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000178726; Expressed in 203 organ(s), highest expression level in left coronary artery.
DR   Genevisible; P07204; HS.
DR   GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005774; C:vacuolar membrane; IEA:Ensembl.
DR   GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR   GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR   GO; GO:0030195; P:negative regulation of blood coagulation; TAS:BHF-UCL.
DR   GO; GO:0051918; P:negative regulation of fibrinolysis; TAS:BHF-UCL.
DR   GO; GO:0010544; P:negative regulation of platelet activation; TAS:BHF-UCL.
DR   GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR   Gene3D; 3.10.100.10; -; 1.
DR   InterPro; IPR001304; C-type_lectin-like.
DR   InterPro; IPR016186; C-type_lectin-like/link_sf.
DR   InterPro; IPR016316; CD141.
DR   InterPro; IPR026823; cEGF.
DR   InterPro; IPR016187; CTDL_fold.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR   InterPro; IPR018097; EGF_Ca-bd_CS.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR015149; Tme5_EGF-like.
DR   PANTHER; PTHR24036:SF5; PTHR24036:SF5; 1.
DR   Pfam; PF12662; cEGF; 1.
DR   Pfam; PF07645; EGF_CA; 1.
DR   Pfam; PF00059; Lectin_C; 1.
DR   Pfam; PF09064; Tme5_EGF_like; 1.
DR   SMART; SM00034; CLECT; 1.
DR   SMART; SM00181; EGF; 6.
DR   SMART; SM00179; EGF_CA; 4.
DR   SUPFAM; SSF56436; SSF56436; 1.
DR   SUPFAM; SSF57184; SSF57184; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 2.
DR   PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR   PROSITE; PS01186; EGF_2; 2.
DR   PROSITE; PS50026; EGF_3; 4.
DR   PROSITE; PS01187; EGF_CA; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Blood coagulation; Complete proteome;
KW   Direct protein sequencing; Disease mutation; Disulfide bond;
KW   EGF-like domain; Glycoprotein; Hemolytic uremic syndrome; Hemostasis;
KW   Hydroxylation; Membrane; Polymorphism; Proteoglycan; Receptor;
KW   Reference proteome; Repeat; Signal; Thrombophilia; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     18       {ECO:0000269|PubMed:2820710}.
FT   CHAIN        19    575       Thrombomodulin.
FT                                /FTId=PRO_0000007771.
FT   TOPO_DOM     19    515       Extracellular. {ECO:0000255}.
FT   TRANSMEM    516    539       Helical. {ECO:0000255}.
FT   TOPO_DOM    540    575       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       31    169       C-type lectin. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00040}.
FT   DOMAIN      241    281       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      284    324       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      325    363       EGF-like 3; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      365    405       EGF-like 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      404    440       EGF-like 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      441    481       EGF-like 6; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REGION      481    515       Involved in alpha-L/beta-2 and alpha-
FT                                M/beta-2 integrin binding.
FT                                {ECO:0000269|PubMed:27055590}.
FT   MOD_RES     342    342       (3R)-3-hydroxyasparagine.
FT                                {ECO:0000269|PubMed:8390446}.
FT   CARBOHYD     47     47       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    115    115       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    116    116       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    382    382       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    409    409       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    490    490       O-linked (Xyl...) (chondroitin sulfate)
FT                                serine.
FT   CARBOHYD    492    492       O-linked (Xyl...) (chondroitin sulfate)
FT                                serine. {ECO:0000269|PubMed:8216207}.
FT   DISULFID    137    158       {ECO:0000250}.
FT   DISULFID    245    256       {ECO:0000250}.
FT   DISULFID    252    265       {ECO:0000250}.
FT   DISULFID    267    280       {ECO:0000250}.
FT   DISULFID    288    296       {ECO:0000250}.
FT   DISULFID    292    308       {ECO:0000250}.
FT   DISULFID    310    323       {ECO:0000250}.
FT   DISULFID    329    340       {ECO:0000250}.
FT   DISULFID    336    349       {ECO:0000250}.
FT   DISULFID    351    362       {ECO:0000250}.
FT   DISULFID    369    378       {ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:1ZAQ,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    374    388       {ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:1ZAQ,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    390    404       {ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:1TMR,
FT                                ECO:0000244|PDB:1ZAQ,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    408    413       {ECO:0000244|PDB:1ADX,
FT                                ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:2ADX,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    417    425       {ECO:0000244|PDB:1ADX,
FT                                ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:2ADX,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    427    439       {ECO:0000244|PDB:1ADX,
FT                                ECO:0000244|PDB:1DQB,
FT                                ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:1EGT,
FT                                ECO:0000244|PDB:1FGD,
FT                                ECO:0000244|PDB:2ADX,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    445    455       {ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    451    464       {ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   DISULFID    466    480       {ECO:0000244|PDB:1DX5,
FT                                ECO:0000244|PDB:3GIS,
FT                                ECO:0000244|PDB:5TO3}.
FT   VARIANT      34     34       D -> E (in AHUS6).
FT                                {ECO:0000269|PubMed:20513133}.
FT                                /FTId=VAR_063673.
FT   VARIANT      43     43       A -> T (in AHUS6; cells transfected with
FT                                the mutant are less effective in
FT                                converting C3b to iC3b on the cell
FT                                surface after complement activation;
FT                                dbSNP:rs1800576).
FT                                {ECO:0000269|PubMed:19625716,
FT                                ECO:0000269|PubMed:9198186,
FT                                ECO:0000269|PubMed:9843165}.
FT                                /FTId=VAR_011368.
FT   VARIANT      53     53       D -> G (in AHUS6; cells transfected with
FT                                the mutant are less effective in
FT                                converting C3b to iC3b on the cell
FT                                surface after complement activation;
FT                                dbSNP:rs121918667).
FT                                {ECO:0000269|PubMed:19625716}.
FT                                /FTId=VAR_063223.
FT   VARIANT      79     79       G -> A (in dbSNP:rs1800577).
FT                                {ECO:0000269|PubMed:9198186}.
FT                                /FTId=VAR_011369.
FT   VARIANT      81     81       V -> L (in AHUS6; cells transfected with
FT                                the mutant are less effective in
FT                                converting C3b to iC3b on the cell
FT                                surface after complement activation;
FT                                dbSNP:rs772288987).
FT                                {ECO:0000269|PubMed:19625716}.
FT                                /FTId=VAR_063224.
FT   VARIANT     162    162       A -> P (in dbSNP:rs36110902).
FT                                /FTId=VAR_049011.
FT   VARIANT     236    236       A -> G (in AHUS6; dbSNP:rs758686992).
FT                                {ECO:0000269|PubMed:20513133}.
FT                                /FTId=VAR_063674.
FT   VARIANT     473    473       A -> V (in dbSNP:rs1042579).
FT                                {ECO:0000269|PubMed:11245641,
FT                                ECO:0000269|PubMed:12139752,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:19625716,
FT                                ECO:0000269|PubMed:9157575,
FT                                ECO:0000269|Ref.5}.
FT                                /FTId=VAR_011370.
FT   VARIANT     486    486       D -> Y (in THPH12 and AHUS6; cells
FT                                transfected with the mutant are less
FT                                effective in converting C3b to iC3b on
FT                                the cell surface after complement
FT                                activation; dbSNP:rs41348347).
FT                                {ECO:0000269|PubMed:12139752,
FT                                ECO:0000269|PubMed:19625716,
FT                                ECO:0000269|PubMed:7811989,
FT                                ECO:0000269|PubMed:9198186}.
FT                                /FTId=VAR_011371.
FT   VARIANT     495    495       P -> S (in AHUS6; cells transfected with
FT                                the mutant are less effective in
FT                                converting C3b to iC3b on the cell
FT                                surface after complement activation;
FT                                dbSNP:rs1800578).
FT                                {ECO:0000269|PubMed:19625716,
FT                                ECO:0000269|PubMed:9198186}.
FT                                /FTId=VAR_011372.
FT   VARIANT     501    501       P -> L (in AHUS6; cells transfected with
FT                                the mutant are less effective in
FT                                converting C3b to iC3b on the cell
FT                                surface after complement activation;
FT                                dbSNP:rs1800579).
FT                                {ECO:0000269|PubMed:19625716,
FT                                ECO:0000269|PubMed:9198186}.
FT                                /FTId=VAR_011373.
FT   HELIX       368    371       {ECO:0000244|PDB:1DX5}.
FT   STRAND      375    380       {ECO:0000244|PDB:1DX5}.
FT   STRAND      382    384       {ECO:0000244|PDB:1DX5}.
FT   STRAND      386    389       {ECO:0000244|PDB:1DX5}.
FT   STRAND      391    393       {ECO:0000244|PDB:1DQB}.
FT   STRAND      394    397       {ECO:0000244|PDB:1DX5}.
FT   STRAND      400    406       {ECO:0000244|PDB:1DX5}.
FT   STRAND      410    414       {ECO:0000244|PDB:1DX5}.
FT   HELIX       419    421       {ECO:0000244|PDB:5TO3}.
FT   STRAND      424    426       {ECO:0000244|PDB:1ADX}.
FT   TURN        428    430       {ECO:0000244|PDB:1DQB}.
FT   STRAND      431    434       {ECO:0000244|PDB:1DX5}.
FT   TURN        435    437       {ECO:0000244|PDB:1DX5}.
FT   STRAND      438    441       {ECO:0000244|PDB:1DX5}.
FT   HELIX       444    447       {ECO:0000244|PDB:1DX5}.
FT   STRAND      452    457       {ECO:0000244|PDB:1DX5}.
FT   STRAND      459    466       {ECO:0000244|PDB:1DX5}.
FT   STRAND      468    471       {ECO:0000244|PDB:1DX5}.
FT   STRAND      473    477       {ECO:0000244|PDB:1DX5}.
SQ   SEQUENCE   575 AA;  60329 MW;  9AF03CD151227D52 CRC64;
     MLGVLVLGAL ALAGLGFPAP AEPQPGGSQC VEHDCFALYP GPATFLNASQ ICDGLRGHLM
     TVRSSVAADV ISLLLNGDGG VGRRRLWIGL QLPPGCGDPK RLGPLRGFQW VTGDNNTSYS
     RWARLDLNGA PLCGPLCVAV SAAEATVPSE PIWEEQQCEV KADGFLCEFH FPATCRPLAV
     EPGAAAAAVS ITYGTPFAAR GADFQALPVG SSAAVAPLGL QLMCTAPPGA VQGHWAREAP
     GAWDCSVENG GCEHACNAIP GAPRCQCPAG AALQADGRSC TASATQSCND LCEHFCVPNP
     DQPGSYSCMC ETGYRLAADQ HRCEDVDDCI LEPSPCPQRC VNTQGGFECH CYPNYDLVDG
     ECVEPVDPCF RANCEYQCQP LNQTSYLCVC AEGFAPIPHE PHRCQMFCNQ TACPADCDPN
     TQASCECPEG YILDDGFICT DIDECENGGF CSGVCHNLPG TFECICGPDS ALARHIGTDC
     DSGKVDGGDS GSGEPPPSPT PGSTLTPPAV GLVHSGLLIG ISIASLCLVV ALLALLCHLR
     KKQGAARAKM EYKCAAPSKE VVLQHVRTER TPQRL
//
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