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Protein

Thrombomodulin

Gene

THBD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • calcium ion binding Source: ProtInc
  • signaling receptor activity Source: ProtInc
  • transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processBlood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiR-HSA-140875 Common Pathway of Fibrin Clot Formation
R-HSA-202733 Cell surface interactions at the vascular wall
SIGNORiP07204

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombomodulin
Short name:
TM
Alternative name(s):
Fetomodulin
CD_antigen: CD141
Gene namesi
Name:THBD
Synonyms:THRM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000178726.6
HGNCiHGNC:11784 THBD
MIMi188040 gene
neXtProtiNX_P07204

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 515ExtracellularSequence analysisAdd BLAST497
Transmembranei516 – 539HelicalSequence analysisAdd BLAST24
Topological domaini540 – 575CytoplasmicSequence analysisAdd BLAST36

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Thrombophilia due to thrombomodulin defect (THPH12)3 Publications
The disease may be caused by mutations affecting the gene represented in this entry. The role of thrombomodulin in thrombosis is controversial. It is likely that genetic or environmental risk factors in addition to THBD variation are involved in the pathogenesis of venous thrombosis.
Disease descriptionA hemostatic disorder characterized by a tendency to thrombosis.
See also OMIM:614486
Hemolytic uremic syndrome atypical 6 (AHUS6)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype.
Disease descriptionAn 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.
See also OMIM:612926
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06367334D → E in AHUS6. 1 Publication1
Natural variantiVAR_01136843A → T in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 3 PublicationsCorresponds to variant dbSNP:rs1800576EnsemblClinVar.1
Natural variantiVAR_06322353D → G in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 1 PublicationCorresponds to variant dbSNP:rs121918667EnsemblClinVar.1
Natural variantiVAR_06322481V → L in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 1 Publication1
Natural variantiVAR_063674236A → G in AHUS6. 1 PublicationCorresponds to variant dbSNP:rs758686992Ensembl.1
Natural variantiVAR_011372495P → S in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 2 PublicationsCorresponds to variant dbSNP:rs1800578EnsemblClinVar.1
Natural variantiVAR_011373501P → L in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 2 PublicationsCorresponds to variant dbSNP:rs1800579EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Hemolytic uremic syndrome, Thrombophilia

Organism-specific databases

DisGeNETi7056
GeneReviewsiTHBD
MalaCardsiTHBD
MIMi612926 phenotype
614486 phenotype
OpenTargetsiENSG00000178726
Orphaneti217023 Atypical hemolytic-uremic syndrome with thrombomodulin anomaly
PharmGKBiPA36496

Chemistry databases

DrugBankiDB00055 Drotrecogin alfa
DB01050 Ibuprofen

Polymorphism and mutation databases

BioMutaiTHBD
DMDMi136170

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
ChainiPRO_000000777119 – 575ThrombomodulinAdd BLAST557

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi47N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi116N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi137 ↔ 158By similarity
Disulfide bondi245 ↔ 256By similarity
Disulfide bondi252 ↔ 265By similarity
Disulfide bondi267 ↔ 280By similarity
Disulfide bondi288 ↔ 296By similarity
Disulfide bondi292 ↔ 308By similarity
Disulfide bondi310 ↔ 323By similarity
Disulfide bondi329 ↔ 340By similarity
Disulfide bondi336 ↔ 349By similarity
Modified residuei342(3R)-3-hydroxyasparagine1 Publication1
Disulfide bondi351 ↔ 362By similarity
Disulfide bondi369 ↔ 378Combined sources
Disulfide bondi374 ↔ 388Combined sources
Glycosylationi382N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi390 ↔ 404Combined sources
Disulfide bondi408 ↔ 413Combined sources
Glycosylationi409N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi417 ↔ 425Combined sources
Disulfide bondi427 ↔ 439Combined sources
Disulfide bondi445 ↔ 455Combined sources
Disulfide bondi451 ↔ 464Combined sources
Disulfide bondi466 ↔ 480Combined sources
Glycosylationi490O-linked (Xyl...) (chondroitin sulfate) serine1
Glycosylationi492O-linked (Xyl...) (chondroitin sulfate) serine1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, Proteoglycan

Proteomic databases

EPDiP07204
MaxQBiP07204
PaxDbiP07204
PeptideAtlasiP07204
PRIDEiP07204
ProteomicsDBi51973

PTM databases

GlyConnecti591
iPTMnetiP07204
PhosphoSitePlusiP07204
SwissPalmiP07204
UniCarbKBiP07204

Expressioni

Tissue specificityi

Endothelial cells are unique in synthesizing thrombomodulin.

Gene expression databases

BgeeiENSG00000178726 Expressed in 203 organ(s), highest expression level in left coronary artery
CleanExiHS_THBD
GenevisibleiP07204 HS

Organism-specific databases

HPAiCAB002425
HPA002982

Interactioni

Subunit structurei

Interacts with ITGAL, ITGAM and ITGB2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
F2P007344EBI-941422,EBI-297094

Protein-protein interaction databases

BioGridi112914, 5 interactors
IntActiP07204, 25 interactors
STRINGi9606.ENSP00000366307

Structurei

Secondary structure

1575
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP07204
SMRiP07204
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07204

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 169C-type lectinPROSITE-ProRule annotationAdd BLAST139
Domaini241 – 281EGF-like 1PROSITE-ProRule annotationAdd BLAST41
Domaini284 – 324EGF-like 2PROSITE-ProRule annotationAdd BLAST41
Domaini325 – 363EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST39
Domaini365 – 405EGF-like 4PROSITE-ProRule annotationAdd BLAST41
Domaini404 – 440EGF-like 5PROSITE-ProRule annotationAdd BLAST37
Domaini441 – 481EGF-like 6; calcium-bindingPROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni481 – 515Involved in alpha-L/beta-2 and alpha-M/beta-2 integrin binding1 PublicationAdd BLAST35

Domaini

Extracellular region (481-515) contains a binding side for alpha-L/beta-2 and alpha-M/beta-2 integrin.1 Publication

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF0T Eukaryota
ENOG410Y5JS LUCA
GeneTreeiENSGT00920000148956
HOGENOMiHOG000114624
HOVERGENiHBG000291
InParanoidiP07204
KOiK03907
OMAiLCGPLCV
OrthoDBiEOG091G06M1
PhylomeDBiP07204
TreeFamiTF330714

Family and domain databases

Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR016316 CD141
IPR026823 cEGF
IPR016187 CTDL_fold
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR009030 Growth_fac_rcpt_cys_sf
IPR015149 Tme5_EGF-like
PANTHERiPTHR24036:SF5 PTHR24036:SF5, 1 hit
PfamiView protein in Pfam
PF12662 cEGF, 1 hit
PF07645 EGF_CA, 1 hit
PF00059 Lectin_C, 1 hit
PF09064 Tme5_EGF_like, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SM00181 EGF, 6 hits
SM00179 EGF_CA, 4 hits
SUPFAMiSSF56436 SSF56436, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 2 hits
PS50041 C_TYPE_LECTIN_2, 1 hit
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 4 hits
PS01187 EGF_CA, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07204-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLGVLVLGAL ALAGLGFPAP AEPQPGGSQC VEHDCFALYP GPATFLNASQ
60 70 80 90 100
ICDGLRGHLM TVRSSVAADV ISLLLNGDGG VGRRRLWIGL QLPPGCGDPK
110 120 130 140 150
RLGPLRGFQW VTGDNNTSYS RWARLDLNGA PLCGPLCVAV SAAEATVPSE
160 170 180 190 200
PIWEEQQCEV KADGFLCEFH FPATCRPLAV EPGAAAAAVS ITYGTPFAAR
210 220 230 240 250
GADFQALPVG SSAAVAPLGL QLMCTAPPGA VQGHWAREAP GAWDCSVENG
260 270 280 290 300
GCEHACNAIP GAPRCQCPAG AALQADGRSC TASATQSCND LCEHFCVPNP
310 320 330 340 350
DQPGSYSCMC ETGYRLAADQ HRCEDVDDCI LEPSPCPQRC VNTQGGFECH
360 370 380 390 400
CYPNYDLVDG ECVEPVDPCF RANCEYQCQP LNQTSYLCVC AEGFAPIPHE
410 420 430 440 450
PHRCQMFCNQ TACPADCDPN TQASCECPEG YILDDGFICT DIDECENGGF
460 470 480 490 500
CSGVCHNLPG TFECICGPDS ALARHIGTDC DSGKVDGGDS GSGEPPPSPT
510 520 530 540 550
PGSTLTPPAV GLVHSGLLIG ISIASLCLVV ALLALLCHLR KKQGAARAKM
560 570
EYKCAAPSKE VVLQHVRTER TPQRL
Length:575
Mass (Da):60,329
Last modified:February 1, 1991 - v2
Checksum:i9AF03CD151227D52
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06367334D → E in AHUS6. 1 Publication1
Natural variantiVAR_01136843A → T in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 3 PublicationsCorresponds to variant dbSNP:rs1800576EnsemblClinVar.1
Natural variantiVAR_06322353D → G in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 1 PublicationCorresponds to variant dbSNP:rs121918667EnsemblClinVar.1
Natural variantiVAR_01136979G → A1 PublicationCorresponds to variant dbSNP:rs1800577Ensembl.1
Natural variantiVAR_06322481V → L in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 1 Publication1
Natural variantiVAR_049011162A → P. Corresponds to variant dbSNP:rs36110902Ensembl.1
Natural variantiVAR_063674236A → G in AHUS6. 1 PublicationCorresponds to variant dbSNP:rs758686992Ensembl.1
Natural variantiVAR_011370473A → V6 PublicationsCorresponds to variant dbSNP:rs1042579EnsemblClinVar.1
Natural variantiVAR_011371486D → Y in THPH12 and AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 4 PublicationsCorresponds to variant dbSNP:rs41348347EnsemblClinVar.1
Natural variantiVAR_011372495P → S in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 2 PublicationsCorresponds to variant dbSNP:rs1800578EnsemblClinVar.1
Natural variantiVAR_011373501P → L in AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation. 2 PublicationsCorresponds to variant dbSNP:rs1800579EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05495 mRNA Translation: CAA29045.1
M16552 mRNA Translation: AAB59508.1
J02973 Genomic DNA Translation: AAA61175.1
D00210 Genomic DNA Translation: BAA00149.1
AF495471 Genomic DNA Translation: AAM03232.1
AL049651 Genomic DNA No translation available.
BC035602 mRNA Translation: AAH35602.2
BC053357 mRNA Translation: AAH53357.1
CCDSiCCDS13148.1
PIRiA41442 THHUB
RefSeqiNP_000352.1, NM_000361.2
UniGeneiHs.2030

Genome annotation databases

EnsembliENST00000377103; ENSP00000366307; ENSG00000178726
GeneIDi7056
KEGGihsa:7056
UCSCiuc002wss.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Thrombomodulin entry

SeattleSNPs
Functional Glycomics Gateway - Glycan Binding

Thrombomodulin

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05495 mRNA Translation: CAA29045.1
M16552 mRNA Translation: AAB59508.1
J02973 Genomic DNA Translation: AAA61175.1
D00210 Genomic DNA Translation: BAA00149.1
AF495471 Genomic DNA Translation: AAM03232.1
AL049651 Genomic DNA No translation available.
BC035602 mRNA Translation: AAH35602.2
BC053357 mRNA Translation: AAH53357.1
CCDSiCCDS13148.1
PIRiA41442 THHUB
RefSeqiNP_000352.1, NM_000361.2
UniGeneiHs.2030

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ADXNMR-A405-444[»]
1DQBNMR-A364-444[»]
1DX5X-ray2.30I/J/K/L363-480[»]
1EGTNMR-A427-444[»]
1FGDNMR-A427-444[»]
1FGENMR-A425-444[»]
1HLTX-ray3.00R426-444[»]
1TMRNMR-A389-405[»]
1ZAQNMR-A364-407[»]
2ADXNMR-A405-444[»]
3GISX-ray2.40X/Y/Z363-483[»]
5TO3X-ray2.34B363-483[»]
ProteinModelPortaliP07204
SMRiP07204
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112914, 5 interactors
IntActiP07204, 25 interactors
STRINGi9606.ENSP00000366307

Chemistry databases

DrugBankiDB00055 Drotrecogin alfa
DB01050 Ibuprofen

PTM databases

GlyConnecti591
iPTMnetiP07204
PhosphoSitePlusiP07204
SwissPalmiP07204
UniCarbKBiP07204

Polymorphism and mutation databases

BioMutaiTHBD
DMDMi136170

Proteomic databases

EPDiP07204
MaxQBiP07204
PaxDbiP07204
PeptideAtlasiP07204
PRIDEiP07204
ProteomicsDBi51973

Protocols and materials databases

DNASUi7056
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377103; ENSP00000366307; ENSG00000178726
GeneIDi7056
KEGGihsa:7056
UCSCiuc002wss.4 human

Organism-specific databases

CTDi7056
DisGeNETi7056
EuPathDBiHostDB:ENSG00000178726.6
GeneCardsiTHBD
GeneReviewsiTHBD
H-InvDBiHIX0174703
HGNCiHGNC:11784 THBD
HPAiCAB002425
HPA002982
MalaCardsiTHBD
MIMi188040 gene
612926 phenotype
614486 phenotype
neXtProtiNX_P07204
OpenTargetsiENSG00000178726
Orphaneti217023 Atypical hemolytic-uremic syndrome with thrombomodulin anomaly
PharmGKBiPA36496
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF0T Eukaryota
ENOG410Y5JS LUCA
GeneTreeiENSGT00920000148956
HOGENOMiHOG000114624
HOVERGENiHBG000291
InParanoidiP07204
KOiK03907
OMAiLCGPLCV
OrthoDBiEOG091G06M1
PhylomeDBiP07204
TreeFamiTF330714

Enzyme and pathway databases

ReactomeiR-HSA-140875 Common Pathway of Fibrin Clot Formation
R-HSA-202733 Cell surface interactions at the vascular wall
SIGNORiP07204

Miscellaneous databases

ChiTaRSiTHBD human
EvolutionaryTraceiP07204
GeneWikiiThrombomodulin
GenomeRNAii7056
PROiPR:P07204
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178726 Expressed in 203 organ(s), highest expression level in left coronary artery
CleanExiHS_THBD
GenevisibleiP07204 HS

Family and domain databases

Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR016316 CD141
IPR026823 cEGF
IPR016187 CTDL_fold
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR009030 Growth_fac_rcpt_cys_sf
IPR015149 Tme5_EGF-like
PANTHERiPTHR24036:SF5 PTHR24036:SF5, 1 hit
PfamiView protein in Pfam
PF12662 cEGF, 1 hit
PF07645 EGF_CA, 1 hit
PF00059 Lectin_C, 1 hit
PF09064 Tme5_EGF_like, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SM00181 EGF, 6 hits
SM00179 EGF_CA, 4 hits
SUPFAMiSSF56436 SSF56436, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 2 hits
PS50041 C_TYPE_LECTIN_2, 1 hit
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 4 hits
PS01187 EGF_CA, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTRBM_HUMAN
AccessioniPrimary (citable) accession number: P07204
Secondary accession number(s): Q8IV29, Q9UC32
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: February 1, 1991
Last modified: September 12, 2018
This is version 224 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health

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