THBD (thrombomodulin)

Gene

• Entrez ID: 7056
• Gene name: Thrombomodulin
• Gene symbol: THBD
• Synonyms: AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM, TM
• Chromosome: 20
• Chromosome location: 20p11.21
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1800576	C>T	Conflicting-interpretations-of-pathogenicity, risk-factor, likely-benign	Missense variant, coding sequence variant
rs1800578	G>A,T	Risk-factor, likely-benign	Missense variant, coding sequence variant
rs1800579	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs16984852	C>A	Pathogenic	5 prime UTR variant
rs121918667	T>C	Risk-factor	Coding sequence variant, missense variant
rs398122807	C>A	Pathogenic	Coding sequence variant, missense variant
rs1347587434	G>A,T	Likely-pathogenic	Synonymous variant, stop gained, coding sequence variant
rs1600409143	G>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1600409323	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1600410451	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017044	hsa-miR-335-5p	Microarray	18185580
MIRT024294	hsa-miR-215-5p	Microarray	19074876
MIRT026159	hsa-miR-192-5p	Microarray	19074876
MIRT636176	hsa-miR-3127-5p	HITS-CLIP	23824327
MIRT636177	hsa-miR-2115-5p	HITS-CLIP	23824327
MIRT636178	hsa-miR-6879-5p	HITS-CLIP	23824327
MIRT636179	hsa-miR-7843-5p	HITS-CLIP	23824327
MIRT636180	hsa-miR-6735-5p	HITS-CLIP	23824327
MIRT636181	hsa-miR-4632-5p	HITS-CLIP	23824327
MIRT636182	hsa-miR-4436b-3p	HITS-CLIP	23824327
MIRT639318	hsa-miR-578	HITS-CLIP	23824327
MIRT639319	hsa-miR-4763-3p	HITS-CLIP	23824327
MIRT639320	hsa-miR-1207-5p	HITS-CLIP	23824327
MIRT639321	hsa-miR-6836-5p	HITS-CLIP	23824327
MIRT639322	hsa-miR-6132	HITS-CLIP	23824327

Transcription factors

Transcription factor	Regulation	Reference
EP300	Repression	15677570
KLF2	Activation	19661484
KLF4	Activation	19661484
NFKB1	Repression	17211835;22406829
PARP1	Activation	21489980
PARP1	Repression	21489980
RARA	Activation	9269772
RARA	Unknown	11036068
RARB	Unknown	11036068
RARG	Unknown	11036068
RELA	Repression	17211835;22406829
RXRA	Unknown	11036068
SP1	Activation	22406829
SP1	Unknown	11036068

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	14691232, 17379830, 32296183
GO:0005615	Component	Extracellular space	IEA
GO:0005774	Component	Vacuolar membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IEA
GO:0007565	Process	Female pregnancy	IEA
GO:0007596	Process	Blood coagulation	TAS
GO:0009897	Component	External side of plasma membrane	IEA
GO:0009986	Component	Cell surface	IDA	17379830
GO:0010165	Process	Response to X-ray	IEA
GO:0010544	Process	Negative regulation of platelet activation	TAS	17379830
GO:0016327	Component	Apicolateral plasma membrane	IEA
GO:0030195	Process	Negative regulation of blood coagulation	TAS	17379830
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0038023	Function	Signaling receptor activity	TAS	2822087
GO:0050900	Process	Leukocyte migration	TAS
GO:0051591	Process	Response to cAMP	IEA
GO:0051918	Process	Negative regulation of fibrinolysis	TAS	17379830

Other IDs

• MIM: 188040
• HGNC: 11784
• e!Ensembl: ENSG00000178726

Protein

• UniProt ID: P07204
• Protein name: Thrombomodulin (TM) (Fetomodulin) (CD antigen CD141)
• Protein function: 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.
• PDB: 1ADX, 1DQB, 1DX5, 1EGT, 1FGD, 1FGE, 1HLT, 1TMR, 1ZAQ, 2ADX, 3GIS, 5TO3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00059	Lectin_C	41 → 169	Lectin C-type domain	Domain
  PF14670	FXa_inhibition	245 → 280		Domain
  PF12662	cEGF	305 → 328	Complement Clr-like EGF-like	Domain

• Sequence:

  MLGVLVLGALALAGLGFPAPAEPQPGGSQCVEHDCFALYPGPATFLNASQICDGLRGHLM
  TVRSSVAADVISLLLNGDGGVGRRRLWIGLQLPPGCGDPKRLGPLRGFQWVTGDNNTSYS
  RWARLDLNGAPLCGPLCVAVSAAEATVPSEPIWEEQQCEVKADGFLCEFHFPATCRPLAV
  EPGAAAAAVSITYGTPFAARGADFQALPVGSSAAVAPLGLQLMCTAPPGAVQGHWAREAP
  GAWDCSVENGGCEHACNAIPGAPRCQCPAGAALQADGRSCTASATQSCNDLCEHFCVPNP
  DQPGSYSCMCETGYRLAADQHRCEDVDDCILEPSPCPQRCVNTQGGFECHCYPNYDLVDG
  ECVEPVDPCFRANCEYQCQPLNQTSYLCVCAEGFAPIPHEPHRCQMFCNQTACPADCDPN
  TQASCECPEGYILDDGFICTDIDECENGGFCSGVCHNLPGTFECICGPDSALARHIGTDC
  DSGKVDGGDSGSGEPPPSPTPGSTLTPPAVGLVHSGLLIGISIASLCLVVALLALLCHLR
  KKQGAARAKMEYKCAAPSKEVVLQHVRTERTPQRL

• Sequence length: 575