Focus on Molecules: ADAMTSL4

Abstract

The ADAMTSL4 gene (MIM:610113) is a member of the ADAMTSL (A Disintegrin AndMetalloproteinase with Thrombospondin Motifs Like) gene family. It is found on chromosome 1q21 and encodes the 1074 amino acid ADAMTS-Like 4 protein (NP_061905). ADAMTSL4 consists of 17 coding exons and two untranslated exons, which span 11.5 kb of genomic sequence. ADAMTS-Like 4 is one of the family of 7 ADAMTS-Like proteins, themselves part of the Thrombospondin type 1 repeat (TSR) superfamily of proteins. These 7 proteins are divided into two distinct clades, of which ADAMTS-Like 4 and ADAMTS-Like 6 form part of one clade, differing fromADAMTS-Like 1, ADAMTS-Like 3 and ADAMTS-Like 7 by lacking immunoglobulin repeat regions (Apte, 2009). The function and disease associations of these proteins are as yet unknown, and thus comparisons between structure and function remain challenging. ADAMTS proteins comprise a protease domain and an ancillary domain, the latter of which determines substrate recognition and function in tissue specificity. ADAMTS-Like proteins are structurally similar to the ADAMTS ancillary domain, including at least one TSR module. Although the TSR repeats are very closely related, ADAMTS-Like proteins lack the proteolytic domains found in ADAMTS proteins. This homology with the ancillary domain may suggest an inhibitory or enhancer relationship between the ADAMTS-Like and ADAMTS proteins. Alternatively this relationship