TRBM_HUMAN
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 03-AUG-2022, entry version 246.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 19-43.
RX PubMed=2820710; DOI=10.1002/j.1460-2075.1987.tb02448.x;
RA Suzuki K., Kusumoto H., Deyashiki Y., Nishioka J., Maruyama I., Zushi M.,
RA Kawahara S., Honda G., Yamamoto S., Horiguchi S.;
RT "Structure and expression of human thrombomodulin, a thrombin receptor on
RT 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 localization
RT 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 of
RT the cDNA and gene predict protein structure and suggest sites of regulatory
RT control.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6425-6429(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2836377; DOI=10.1093/oxfordjournals.jbchem.a122261;
RA Shirai T., Shiojiri S., Ito H., Yamamoto S., Kusumoto H., Deyashiki Y.,
RA Maruyama I., Suzuki K.;
RT "Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed
RT 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 project:
RT 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 in
RT 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; DOI=10.1093/oxfordjournals.jbchem.a124063;
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 thrombomodulin
RT 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-year-old
RT 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 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., Stubbs P.J.,
RA Manger Cats V., Ireland H.;
RT "A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and
RT 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; SER-495
RP 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., Ferrell G.,
RA Del-Favero J., Plaisance S., Claes B., Lambrechts D., Zoja C., Remuzzi G.,
RA 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 patients
RT with atypical hemolytic uremic syndrome.";
RL Hum. Mutat. 31:E1445-E1460(2010).
CC -!- FUNCTION: Thrombomodulin is a specific endothelial cell receptor that
CC forms a 1:1 stoichiometric complex with thrombin. This complex is
CC responsible for the conversion of protein C to the activated protein C
CC (protein Ca). Once evolved, protein Ca scissions the activated
CC cofactors of the coagulation mechanism, factor Va and factor VIIIa, and
CC thereby reduces the amount of thrombin generated.
CC -!- SUBUNIT: Interacts with ITGAL, ITGAM and ITGB2.
CC {ECO:0000269|PubMed:27055590}.
CC -!- INTERACTION:
CC P07204; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-941422, EBI-11957045;
CC P07204; P55056: APOC4; NbExp=3; IntAct=EBI-941422, EBI-18302142;
CC P07204; Q13520: AQP6; NbExp=3; IntAct=EBI-941422, EBI-13059134;
CC P07204; P11912: CD79A; NbExp=3; IntAct=EBI-941422, EBI-7797864;
CC P07204; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-941422, EBI-7062247;
CC P07204; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-941422, EBI-2680384;
CC P07204; Q15125: EBP; NbExp=3; IntAct=EBI-941422, EBI-3915253;
CC P07204; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-941422, EBI-781551;
CC P07204; P00734: F2; NbExp=4; IntAct=EBI-941422, EBI-297094;
CC P07204; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-941422, EBI-18304435;
CC P07204; Q8TED1: GPX8; NbExp=3; IntAct=EBI-941422, EBI-11721746;
CC P07204; P43628: KIR2DL3; NbExp=3; IntAct=EBI-941422, EBI-8632435;
CC P07204; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-941422, EBI-6163737;
CC P07204; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-941422, EBI-3923617;
CC P07204; P15941-11: MUC1; NbExp=3; IntAct=EBI-941422, EBI-17263240;
CC P07204; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-941422, EBI-716063;
CC P07204; Q9UPV7: PHF24; NbExp=3; IntAct=EBI-941422, EBI-17717171;
CC P07204; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-941422, EBI-17589229;
CC P07204; Q9BZV2: SLC19A3; NbExp=3; IntAct=EBI-941422, EBI-3923779;
CC P07204; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-941422, EBI-17295964;
CC P07204; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-941422, EBI-8638294;
CC P07204; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-941422, EBI-11722971;
CC P07204; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-941422, EBI-2548832;
CC P07204; Q9Y320: TMX2; NbExp=3; IntAct=EBI-941422, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane 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 aspartate
CC 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, ECO:0000269|PubMed:7811989,
CC ECO:0000269|PubMed:9198186}. Note=The disease may be caused by variants
CC affecting the gene represented in this entry. The role of
CC thrombomodulin in thrombosis is controversial. It is likely that
CC genetic or environmental risk factors in addition to THBD variation are
CC involved in the pathogenesis of venous thrombosis.
CC -!- DISEASE: Hemolytic uremic syndrome atypical 6 (AHUS6) [MIM:612926]: An
CC atypical form of hemolytic uremic syndrome. It is a complex genetic
CC disease characterized by microangiopathic hemolytic anemia,
CC thrombocytopenia, renal failure and absence of episodes of
CC enterocolitis and diarrhea. In contrast to typical hemolytic uremic
CC syndrome, atypical forms have a poorer prognosis, with higher death
CC rates and frequent progression to end-stage renal disease.
CC {ECO:0000269|PubMed:19625716, ECO:0000269|PubMed:20513133}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry. Other genes may play a role in
CC 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";
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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 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 PDB; 7T4R; EM; 3.30 A; A=1-516.
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 PDBsum; 7T4R; -.
DR AlphaFoldDB; P07204; -.
DR BMRB; P07204; -.
DR SMR; P07204; -.
DR BioGRID; 112914; 33.
DR ComplexPortal; CPX-6223; Thrombin-Thrombomodulin complex.
DR IntAct; P07204; 27.
DR STRING; 9606.ENSP00000366307; -.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB00055; Drotrecogin alfa.
DR DrugBank; DB01050; Ibuprofen.
DR GlyConnect; 591; 2 O-Linked glycans.
DR GlyGen; P07204; 8 sites, 2 O-linked glycans (1 site).
DR iPTMnet; P07204; -.
DR MetOSite; P07204; -.
DR PhosphoSitePlus; P07204; -.
DR SwissPalm; P07204; -.
DR BioMuta; THBD; -.
DR DMDM; 136170; -.
DR EPD; P07204; -.
DR jPOST; P07204; -.
DR MassIVE; P07204; -.
DR MaxQB; P07204; -.
DR PaxDb; P07204; -.
DR PeptideAtlas; P07204; -.
DR PRIDE; P07204; -.
DR ProteomicsDB; 51973; -.
DR Antibodypedia; 792; 1016 antibodies from 44 providers.
DR DNASU; 7056; -.
DR Ensembl; ENST00000377103.3; ENSP00000366307.2; ENSG00000178726.7.
DR GeneID; 7056; -.
DR KEGG; hsa:7056; -.
DR MANE-Select; ENST00000377103.3; ENSP00000366307.2; NM_000361.3; NP_000352.1.
DR UCSC; uc002wss.4; human.
DR CTD; 7056; -.
DR DisGeNET; 7056; -.
DR GeneCards; THBD; -.
DR GeneReviews; THBD; -.
DR HGNC; HGNC:11784; THBD.
DR HPA; ENSG00000178726; Low tissue specificity.
DR MalaCards; THBD; -.
DR MIM; 188040; gene.
DR MIM; 612926; phenotype.
DR MIM; 614486; phenotype.
DR neXtProt; NX_P07204; -.
DR OpenTargets; ENSG00000178726; -.
DR Orphanet; 544472; Atypical hemolytic uremic syndrome with complement gene abnormality.
DR Orphanet; 436169; Thrombomodulin-related bleeding disorder.
DR PharmGKB; PA36496; -.
DR VEuPathDB; HostDB:ENSG00000178726; -.
DR eggNOG; ENOG502R1T7; Eukaryota.
DR GeneTree; ENSGT00940000163276; -.
DR HOGENOM; CLU_027075_2_1_1; -.
DR InParanoid; P07204; -.
DR OMA; HRCQMFC; -.
DR OrthoDB; 1174178at2759; -.
DR PhylomeDB; P07204; -.
DR TreeFam; TF330714; -.
DR PathwayCommons; P07204; -.
DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR SignaLink; P07204; -.
DR SIGNOR; P07204; -.
DR BioGRID-ORCS; 7056; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; THBD; human.
DR EvolutionaryTrace; P07204; -.
DR GeneWiki; Thrombomodulin; -.
DR GenomeRNAi; 7056; -.
DR Pharos; P07204; Tbio.
DR PRO; PR:P07204; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P07204; protein.
DR Bgee; ENSG00000178726; Expressed in gingival epithelium and 183 other tissues.
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:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal.
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:ProtInc.
DR GO; GO:0072377; P:blood coagulation, common pathway; IC:ComplexPortal.
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:0006508; P:proteolysis; IC:ComplexPortal.
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 GO; GO:0031638; P:zymogen activation; IC:ComplexPortal.
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; 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; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain; Glycoprotein;
KW Hemolytic uremic syndrome; Hemostasis; Hydroxylation; Membrane;
KW Proteoglycan; Receptor; Reference proteome; Repeat; Signal; Thrombophilia;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:2820710"
FT CHAIN 19..575
FT /note="Thrombomodulin"
FT /id="PRO_0000007771"
FT TOPO_DOM 19..515
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 516..539
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..169
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DOMAIN 241..281
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 284..324
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 325..363
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 365..405
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 404..440
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 441..481
FT /note="EGF-like 6; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 481..515
FT /note="Involved in alpha-L/beta-2 and alpha-M/beta-2
FT integrin binding"
FT /evidence="ECO:0000269|PubMed:27055590"
FT REGION 484..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 342
FT /note="(3R)-3-hydroxyasparagine"
FT /evidence="ECO:0000269|PubMed:8390446"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 490
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT CARBOHYD 492
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000269|PubMed:8216207"
FT DISULFID 137..158
FT /evidence="ECO:0000250"
FT DISULFID 245..256
FT /evidence="ECO:0000250"
FT DISULFID 252..265
FT /evidence="ECO:0000250"
FT DISULFID 267..280
FT /evidence="ECO:0000250"
FT DISULFID 288..296
FT /evidence="ECO:0000250"
FT DISULFID 292..308
FT /evidence="ECO:0000250"
FT DISULFID 310..323
FT /evidence="ECO:0000250"
FT DISULFID 329..340
FT /evidence="ECO:0000250"
FT DISULFID 336..349
FT /evidence="ECO:0000250"
FT DISULFID 351..362
FT /evidence="ECO:0000250"
FT DISULFID 369..378
FT /evidence="ECO:0007744|PDB:1DQB, ECO:0007744|PDB:1DX5,
FT ECO:0007744|PDB:1ZAQ, ECO:0007744|PDB:3GIS,
FT ECO:0007744|PDB:5TO3"
FT DISULFID 374..388
FT /evidence="ECO:0007744|PDB:1DQB, ECO:0007744|PDB:1DX5,
FT ECO:0007744|PDB:1ZAQ, ECO:0007744|PDB:3GIS,
FT ECO:0007744|PDB:5TO3"
FT DISULFID 390..404
FT /evidence="ECO:0007744|PDB:1DQB, ECO:0007744|PDB:1DX5,
FT ECO:0007744|PDB:1TMR, ECO:0007744|PDB:1ZAQ,
FT ECO:0007744|PDB:3GIS, ECO:0007744|PDB:5TO3"
FT DISULFID 408..413
FT /evidence="ECO:0007744|PDB:1ADX, ECO:0007744|PDB:1DQB,
FT ECO:0007744|PDB:1DX5, ECO:0007744|PDB:2ADX,
FT ECO:0007744|PDB:3GIS, ECO:0007744|PDB:5TO3"
FT DISULFID 417..425
FT /evidence="ECO:0007744|PDB:1ADX, ECO:0007744|PDB:1DQB,
FT ECO:0007744|PDB:1DX5, ECO:0007744|PDB:2ADX,
FT ECO:0007744|PDB:3GIS, ECO:0007744|PDB:5TO3"
FT DISULFID 427..439
FT /evidence="ECO:0007744|PDB:1ADX, ECO:0007744|PDB:1DQB,
FT ECO:0007744|PDB:1DX5, ECO:0007744|PDB:1EGT,
FT ECO:0007744|PDB:1FGD, ECO:0007744|PDB:2ADX,
FT ECO:0007744|PDB:3GIS, ECO:0007744|PDB:5TO3"
FT DISULFID 445..455
FT /evidence="ECO:0007744|PDB:1DX5, ECO:0007744|PDB:3GIS,
FT ECO:0007744|PDB:5TO3"
FT DISULFID 451..464
FT /evidence="ECO:0007744|PDB:1DX5, ECO:0007744|PDB:3GIS,
FT ECO:0007744|PDB:5TO3"
FT DISULFID 466..480
FT /evidence="ECO:0007744|PDB:1DX5, ECO:0007744|PDB:3GIS,
FT ECO:0007744|PDB:5TO3"
FT VARIANT 34
FT /note="D -> E (in AHUS6)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063673"
FT VARIANT 43
FT /note="A -> T (in AHUS6; cells transfected with the mutant
FT are less effective in converting C3b to iC3b on the cell
FT surface after complement activation; dbSNP:rs1800576)"
FT /evidence="ECO:0000269|PubMed:19625716,
FT ECO:0000269|PubMed:9198186, ECO:0000269|PubMed:9843165"
FT /id="VAR_011368"
FT VARIANT 53
FT /note="D -> G (in AHUS6; cells transfected with the mutant
FT are less effective in converting C3b to iC3b on the cell
FT surface after complement activation; dbSNP:rs121918667)"
FT /evidence="ECO:0000269|PubMed:19625716"
FT /id="VAR_063223"
FT VARIANT 79
FT /note="G -> A (in dbSNP:rs1800577)"
FT /evidence="ECO:0000269|PubMed:9198186"
FT /id="VAR_011369"
FT VARIANT 81
FT /note="V -> L (in AHUS6; cells transfected with the mutant
FT are less effective in converting C3b to iC3b on the cell
FT surface after complement activation; dbSNP:rs772288987)"
FT /evidence="ECO:0000269|PubMed:19625716"
FT /id="VAR_063224"
FT VARIANT 162
FT /note="A -> P (in dbSNP:rs36110902)"
FT /id="VAR_049011"
FT VARIANT 236
FT /note="A -> G (in AHUS6; dbSNP:rs758686992)"
FT /evidence="ECO:0000269|PubMed:20513133"
FT /id="VAR_063674"
FT VARIANT 473
FT /note="A -> V (in dbSNP:rs1042579)"
FT /evidence="ECO:0000269|PubMed:11245641,
FT ECO:0000269|PubMed:12139752, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19625716, ECO:0000269|PubMed:9157575,
FT ECO:0000269|Ref.5"
FT /id="VAR_011370"
FT VARIANT 486
FT /note="D -> Y (in THPH12 and AHUS6; cells transfected with
FT the mutant are less effective in converting C3b to iC3b on
FT the cell surface after complement activation;
FT dbSNP:rs41348347)"
FT /evidence="ECO:0000269|PubMed:12139752,
FT ECO:0000269|PubMed:19625716, ECO:0000269|PubMed:7811989,
FT ECO:0000269|PubMed:9198186"
FT /id="VAR_011371"
FT VARIANT 495
FT /note="P -> S (in AHUS6; cells transfected with the mutant
FT are less effective in converting C3b to iC3b on the cell
FT surface after complement activation; dbSNP:rs1800578)"
FT /evidence="ECO:0000269|PubMed:19625716,
FT ECO:0000269|PubMed:9198186"
FT /id="VAR_011372"
FT VARIANT 501
FT /note="P -> L (in AHUS6; cells transfected with the mutant
FT are less effective in converting C3b to iC3b on the cell
FT surface after complement activation; dbSNP:rs1800579)"
FT /evidence="ECO:0000269|PubMed:19625716,
FT ECO:0000269|PubMed:9198186"
FT /id="VAR_011373"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:1DQB"
FT STRAND 394..397
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:1DX5"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:5TO3"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:1ADX"
FT TURN 428..430
FT /evidence="ECO:0007829|PDB:1DQB"
FT STRAND 431..434
FT /evidence="ECO:0007829|PDB:1DX5"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:1DX5"
FT HELIX 444..447
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 459..466
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 468..471
FT /evidence="ECO:0007829|PDB:1DX5"
FT STRAND 473..477
FT /evidence="ECO:0007829|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
