ADAMTS13
Domain
The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency.
The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction.
Function
Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
Involvement in disease
Thrombotic thrombocytopenic purpura, hereditary
TTP
An autosomal recessive hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS13. May also be C-glycosylated on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and also N-glycosylated. These other glycosylations can also facilitate secretion.
The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.
Tissue Specificity
Plasma. Expressed primarily in liver.
Cellular localization
- Secreted
- Secretion enhanced by O-fucosylation of TSP type-1 repeats.
Alternative names
C9orf8, UNQ6102/PRO20085, ADAMTS13, A disintegrin and metalloproteinase with thrombospondin motifs 13, ADAM-TS 13, ADAM-TS13, ADAMTS-13, von Willebrand factor-cleaving protease, vWF-CP, vWF-cleaving protease