RelevanceADAMTS19 is a member of the ADAMs family of proteinases with Thrombospondin motifs. ADAMTS19 is closest in homology to ADAMTS17, sharing 54% overall identity. Like ADAMTS17, ADAMTS19 has a PLAC (Protease and LACunin) domain at the carboxyterminal end. The PLAC domain contains a 6-cysteine conserved repeat, first described in lacunin, an ADAMTS-like protein. ADAMTS19 was first described in fetal human lung, and in adult endothelium and ovary. ADAMTS19 was also found to be overexpressed in osteoscarcoma cell lines, and in mouse female gonadal tissue. ADAMTS19, like ADAMTS17, has a total of 5 thrombospondin-like domains. The first TSP1 domain begins shortly after the catalytic and disintegrin domains. TSP1 domains 2-5 are separated from the first TSP domain by the cysteine-rich domain and a spacer domain. Like other members of the ADAMTS family, the TSP1 motifs are thought to bind ADAMTS19 to the ECM. The PLAC domain follows the final TSP1 repeat. ADAMTS19 contains a prohormone-convertase cleavage site; the predicted PC cleavage site is the RQKR277 sequence, in the 1207 and 798 amino acid forms. There are several paired basic sequences available in the different ADAMTS19 isoforms, and they may be cleaved by different PCs under different conditions. The catalytic site of ADAMTS19 is not typical of other metalloproteinase catalytic domains, which have an HExxHxxxxxH sequence. ADAMTS19 has HDxxHxxxxxH motif instead, and this may alter the catalytic function relative to the other MPs. Several different splice variants of ADAMTS19 have been reported. The longest human ADAMTS19 message encodes a protein of 1207 amino acids with predicted mass of 134.1 kDa and a pI of 8.55. A 798 amino acid version with predicted mass of 87.84 kDa and a pI of 6.05 ends shortly after the catalytic domain. Two shorter versions of 454 and 56 amino acids are reported, the shortest lacking the MP domain. The 454 amino acid version starts just before the MP domain, and ends before the TSP1 domains, and it is unclear if this form is proteolytically active. Little more is known about the functions, expression or distribution of the ADAMTS19 variants.