A DISINTEGRIN-LIKE AND METALLOPROTEINASE WITH THROMBOSPONDIN TYPE 1 MOTIF, 8; ADAMTS8

Alternative titles; symbols

• METH2

HGNC Approved Gene Symbol: ADAMTS8

Cytogenetic location: 11q24.3 Genomic coordinates (GRCh38): 11:130,404,922-130,428,608 (from NCBI)

▼ Description
ADAMTS8 is a member of the large ADAMTS family of zinc-dependent proteases. For a general description of the ADAMTS gene family, see ADAMTS1 (605174).

▼ Cloning and Expression
By searching an EST database for sequences containing the antiangiogenic motif of thrombospondin-1 (THBS1; 188060), Vazquez et al. (1999) identified heart and lung cDNAs encoding ADAMTS1 and ADAMTS8, which they called METH1 and METH2, respectively. Sequence analysis predicted that the 890-amino acid ADAMTS8 protein shares 52% sequence identity with ADAMTS1. ADAMTS8 is a secreted protein that has an N-terminal signal peptide, a zinc metalloprotease domain containing a zinc-binding site, and a cysteine-rich region containing 2 putative disintegrin loops. The C terminus of ADAMTS8 has 2 heparin-binding thrombospondin repeats with 6 cys and 3 trp residues. Southern blot analysis showed that ADAMTS8 is a single-copy gene distinct from that encoding ADAMTS1. Northern blot analysis detected highest expression of a 3.7-kb ADAMTS8 transcript in adult and fetal lung, with lower expression in brain, placenta, heart, and stomach, as well as fetal brain and kidney. Expression was also detected in a colon carcinoma cell line. SDS-PAGE analysis demonstrated that ADAMTS8 is expressed as a 98-kD protein, a 79-kD protein after cleavage at the subtilisin site, or as a 64-kD protein, which is most abundant, generated by an additional processing event.

▼ Gene Function
Vazquez et al. (1999) performed functional studies demonstrating that ADAMTS8 disrupts angiogenesis in vivo and in vitro more efficiently than THBS1 or endostatin (120328) but somewhat less efficiently than ADAMTS1.

▼ Mapping
By interspecific backcross analysis, Georgiadis et al. (1999) mapped the mouse Adamts8 gene to chromosome 9 in a region showing homology of synteny with human 11q23-qter. They mapped the human ADAMTS8 gene to 11q25 by PCR analysis of a radiation hybrid mapping panel.