THBD

Protein identityUniProt · HPA

UniProt accession

P07204

Gene

THBD

Ensembl

ENSG00000178726

Chromosome

20

Canonical length

575 aa

Protein class

Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

The protein encoded by this intronless gene is an endothelial-specific type I membrane receptor that binds thrombin. This binding results in the activation of protein C, which degrades clotting factors Va and VIIIa and reduces the amount of thrombin generated. Mutations in this gene are a cause of thromboembolic disease, also known as inherited thrombophilia. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

575 residues, UniProt reviewed canonical sequence.

>P07204|THBD
     1  MLGVLVLGAL ALAGLGFPAP AEPQPGGSQC VEHDCFALYP GPATFLNASQ ICDGLRGHLM
    61  TVRSSVAADV ISLLLNGDGG VGRRRLWIGL QLPPGCGDPK RLGPLRGFQW VTGDNNTSYS
   121  RWARLDLNGA PLCGPLCVAV SAAEATVPSE PIWEEQQCEV KADGFLCEFH FPATCRPLAV
   181  EPGAAAAAVS ITYGTPFAAR GADFQALPVG SSAAVAPLGL QLMCTAPPGA VQGHWAREAP
   241  GAWDCSVENG GCEHACNAIP GAPRCQCPAG AALQADGRSC TASATQSCND LCEHFCVPNP
   301  DQPGSYSCMC ETGYRLAADQ HRCEDVDDCI LEPSPCPQRC VNTQGGFECH CYPNYDLVDG
   361  ECVEPVDPCF RANCEYQCQP LNQTSYLCVC AEGFAPIPHE PHRCQMFCNQ TACPADCDPN
   421  TQASCECPEG YILDDGFICT DIDECENGGF CSGVCHNLPG TFECICGPDS ALARHIGTDC
   481  DSGKVDGGDS GSGEPPPSPT PGSTLTPPAV GLVHSGLLIG ISIASLCLVV ALLALLCHLR
   541  KKQGAARAKM EYKCAAPSKE VVLQHVRTER TPQRL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against THBD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

69 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about THBD.

Disease | AllUniProt

Conditions THBD is implicated in, by any mechanism.

• Thrombophilia due to thrombomodulin defect (THPH12) MIM:614486
• Hemolytic uremic syndrome, atypical, 6 (AHUS6) MIM:612926

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 702 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Thrombomodulin-related bleeding disorder
• Abnormal bleeding
• Atypical hemolytic-uremic syndrome with thrombomodulin anomaly
• Thrombocytopenia
• See cases

Disease | AutoantibodyPubMed

Conditions in which antibodies against THBD are reported. Each links to that disease's full target list.

• Thrombosis 3

ReferencesPubMed · IEDB

Publications for THBD from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.79

gnomAD pLI

0.05

gnomAD missense Z

0.6

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• blood coagulation, common pathway
• female pregnancy
• negative regulation of blood coagulation
• negative regulation of fibrinolysis
• negative regulation of platelet activation
• proteolysis
• response to cAMP
• response to lipopolysaccharide
• response to X-ray
• zymogen activation

Molecular functions

• calcium ion binding
• signaling receptor activity
• transmembrane signaling receptor activity

Cellular components

• apicolateral plasma membrane
• cell surface
• external side of plasma membrane
• extracellular space
• plasma membrane
• serine-type endopeptidase complex
• vacuolar membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• C-type lectin-like
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• C-type lectin-like/link domain superfamily
• C-type lectin fold
• EGF-like calcium-binding, conserved site
• Complement Clr-like EGF domain
• NOTCH1, EGF-like calcium-binding domain
• Thrombomodulin-like domain
• Lectin C-type domain
• Calcium-binding EGF domain
• Complement Clr-like EGF-like
• Coagulation Factor Xa inhibitory site
• Thrombomodulin-like domain
• Thrombomodulin-like, EGF-like
• Spindle_Organization_and_Thrombomodulin
• Thrombomodulin like fifth domain, EGF-like

KeywordsUniProt

• Blood coagulation
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Hemolytic uremic syndrome
• Hemostasis
• Hydroxylation
• Membrane
• Proteoglycan
• Receptor
• Repeat
• Signal
• Thrombophilia
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of THBD in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANGP1
• ANGP2
• HMGB1
• ITGAL
• ITGAM
• ITGB2
• PF4
• ANGPT1
• ANGPT2