ADAMTS13

ADAMTS13
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3GHM, 3GHN
Identifiers
Aliases	ADAMTS13, ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP, ADAM metallopeptidase with thrombospondin type 1 motif 13
External IDs	OMIM: 604134 MGI: 2685556 HomoloGene: 16372 GeneCards: ADAMTS13
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.2 Start 133,414,358 bp[1] End 133,459,402 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 A3 Start 26,863,428 bp[2] End 26,899,640 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver right uterine tube pituitary gland Brodmann area 9 putamen anterior pituitary hippocampus proper temporal lobe amygdala nucleus accumbens Top expressed in liver morula bone marrow esophagus hippocampus proper yolk sac superior frontal gyrus spleen colon hypothalamus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding endopeptidase activity metal ion binding integrin binding peptidase activity protein binding metalloendopeptidase activity hydrolase activity metallopeptidase activity zinc ion binding Cellular component endoplasmic reticulum lumen extracellular region cell surface extracellular space extracellular matrix Biological process hemostasis glycoprotein metabolic process response to interleukin-4 response to interferon-gamma protein processing blood coagulation proteolysis platelet activation response to tumor necrosis factor integrin-mediated signaling pathway cell-matrix adhesion response to toxic substance peptide catabolic process response to potassium ion cellular response to interferon-gamma cellular response to lipopolysaccharide response to amine cellular response to interleukin-4 cellular response to tumor necrosis factor Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11093 279028 Ensembl ENSG00000160323 ENSG00000281244 ENSMUSG00000014852 UniProt Q76LX8 Q769J6 RefSeq (mRNA) NM_139025 NM_139026 NM_139027 NM_139028 NM_001001322 NM_001290463 NM_001290464 NM_001290465 RefSeq (protein) NP_620594 NP_620595 NP_620596 NP_001001322 NP_001277392 NP_001277393 NP_001277394 Location (UCSC) Chr 9: 133.41 – 133.46 Mb Chr 2: 26.86 – 26.9 Mb PubMed search [3] [4]
Wikidata
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ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted into the blood and degrades large vWf multimers, decreasing their activity, hence ADAMTS13 acts to reduce thrombus formation.^[5]

Genetics

The ADAMTS13 gene maps to the ninth chromosome (9q34).^[5]

Discovery

Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterized in its familial form by the presence in plasma of unusually large von Willebrand factor multimers (ULVWF).^[5]

In 1994, vWF was shown to be cleaved between a tyrosine at position 1605 and a methionine at 1606 by a plasma metalloprotease enzyme when it was exposed to high levels of shear stress. In 1996, two research groups independently further characterized this enzyme. In the next two years, the same two groups showed that the congenital deficiency of a vWF-cleaving protease was associated with formation of platelet microthrombi in the small blood vessels. In addition, they reported that IgG antibodies directed against this same enzyme caused TTP in a majority of non-familial cases.^[5]

Proteomics

Genomically, ADAMTS13 shares many properties with the 19 member ADAMTS family, all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacent disintegrin domain and one or more thrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it is not anchored in the cell membrane.^[5]

Role in disease

Deficiency of ADAMTS13 was originally discovered in Upshaw Schulman Syndrome, the recurring familial form of thrombotic thrombocytopenic purpura. By that time it was already suspected that TTP occurred in the autoimmune form as well, owing to its response to plasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specific epitopes on its surface have been shown to be the target of inhibitory antibodies.^[5][6][7]

Low levels of ADAMTS13 are also associated with an increased risk of arterial thrombosis,^[8] including myocardial infarction^[9] and cerebrovascular disease.^[10][11]

Finally, since the link between aortic valve stenosis and angiodysplasia was proven to be due to high shear stress (Heyde's syndrome), it has been accepted that increased exposure of vWf to ADAMTS13 due to various reasons would predispose to bleeding by causing increased degradation of vWf. This phenomenon is characterised by a form of von Willebrand disease (type 2a).^[5]

See also

• ADAMTS5

References

Further reading

External links

• The MEROPS online database for peptidases and their inhibitors: M12.241
• Online Mendelian Inheritance in Man (OMIM): 274150
• Secreted protein database entry
• Human ADAMTS13 genome location and ADAMTS13 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q76LX8 (A disintegrin and metalloproteinase with thrombospondin motifs 13) at the PDBe-KB.