Anti-ADAMTS6 antibody - First furin cleavage site of the propeptide domain (ab39888)

Relevance

ADAMTS6 was first described along with ADAMTS5 and ADAMTS7 in database searches for proteases containing the metalloprotease domain signature. A member of the metalloproteinase family containing disintegrin-like domains (ADAMs) the function of ADAMTS6 is still poorly understood, and as of this writing no substrates have been shown to be cleaved by ADAMTS6. ADAMTS6 contains the canonical HExxHxxxxxH zinc metalloproteinase motif, and is likely to be an active protease. In addition to the metalloprotease domain, ADAMTS6 has a propeptide domain, a Prohormone Convertase (PC, furin) cleavage site, a cysteine-rich domain, a spacer domain and five thrombospondin 1 like domains. The domain structure of ADAMTS6 is thus most like ADAMTS16 and ADAMTS19. ADAMTS6 does not have a transmembrane domain, unlike many of the ADAMs proteases, and is a secreted protein. Other ADAMTSs family members (ADAMTS4, ADAMTS5) have been more thoroughly studied, and are known to play key roles in aggrecan turnover. Analysis of breast cancer cell lines and RPE cells in the eye show elevated expression of ADAMTS6, and the original paper cited low levels of expression in the placenta. Three human sequences are currently reported, 1117, 860 and 468 amino acids in length respectively. The 860 amino acid sequence has a shorter spacer after the catalytic domain, and ends in the second thrombospondin domain. The 468 amino acid sequence ends at the start of the disintegrin domain. It remains to be seen where these different splice variants are expressed. The 1117 amino acid protein has a predicted mass of 125.27 kDa, the 860 form 97.11 kDa and the 468 form 53.12 kDa, but glycosylation and the abundance of cysteine residues gives ADAMTS6 a greater apparent molecular weight on reduced SDS PAGE gels. The furin consensus motif in ADAMTS6 means that the protein is likely to be cleaved when it is secreted.

Cellular localization

Secreted protein; extracellular space; extracellular matrix.

Alternative names

Database links