HGNC Approved Gene Symbol: ADAMTS20Cytogenetic location: 12q12 Genomic coordinates (GRCh38): 12:43,352,842-43,552,202 (from NCBI)▼ DescriptionADAMTS20 is a m...
HGNC Approved Gene Symbol: ADAMTS20
Cytogenetic location: 12q12 Genomic coordinates (GRCh38): 12:43,352,842-43,552,202 (from NCBI)
ADAMTS20 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 database analysis using known ADAMTS sequences as probe, followed by PCR of human erythroleukemia and lung cancer cell line cDNA, Somerville et al. (2003) cloned ADAMTS20. The deduced 1,911-amino acid protein has a calculated molecular mass of 214 kD, and the mature enzyme has a predicted molecular mass of 185 kD. ADAMTS20 has a C-terminal array of 14 thrombospondin type I (THBS1; 188060) repeats (TSRs), and the cysteine signatures of ADAMTS20 modules in all but 1 module, TSR-13, contain an even number of cysteines with potential to form intrachain disulfide bonds and share similarity with several other ADAMTS family members. ADAMTS20 contains a signal peptide, 3 consensus furin cleavage sites, 15 N-linked glycosylation sites, 1 potential site for glycosaminoglycan (GAG) attachment, 2 CSVTCG motifs that may mediate binding to the cell surface molecule CD36 (173510), and 2 BBXB motifs that mediate heparin and sulfatide binding. The ADAMTS20 zinc-binding site shares similarity with that of ADAMTS7 (605009) and ADAMTS12 (606184). ADAMTS20 shares 48% amino acid identity with ADAMTS9 (605421). Northern blot analysis did not detect expression of ADAMTS20 mRNA in adult human tissues. RT-PCR and RNA in situ hybridization detected low expression in epithelial cells of breast and lung.
Llamazares et al. (2003) independently cloned human and mouse ADAMTS20. ADAMTS20 shares 69% amino acid identity with its mouse homolog. The authors identified a short isoform of ADAMTS20 with 11 TSRs due to alternative splicing. Northern blot analysis of polyA(+) RNA from human tissues detected a 7-kb transcript in testis, prostate, ovary, heart, placenta, lung, and pancreas. RT-PCR analysis of primary tumors and adjacent normal tissue showed overexpression of ADAMTS20 in several brain, colon, and breast carcinomas when compared to the low or undetectable expression in corresponding normal tissues. Western blot analysis detected a 70-kD band in mouse testis and brain tissues.
▼ Gene Structure
Somerville et al. (2003) determined that the ADAMTS20 gene contains 39 exons spanning 200 kb.
By genomic sequence analysis, Somerville et al. (2003) mapped the ADAMTS20 gene to chromosome 12q11.
▼ Gene Function
Llamazares et al. (2003) showed that the mouse Adamts20 catalytic domain displayed proteolytic activity and that metalloprotease inhibitors abolished enzyme activity.
Nandadasa et al. (2019) found that ADAMTS9 and ADAMTS20 localized at the base of primary cilium of mouse and human cells. ADAMTS9 and ADAMTS20 acted as proteases for cleavage of the extracellular matrix (ECM) component versican (VCAN; 118661), and ADAMTS9 and ADAMTS20 catalytic activities were essential and functionally redundant during ciliogenesis. Loss of ADAMTS9 significantly reduced ciliogenesis, which could be restored by overexpression of ADAMTS9 or ADAMTS20.
▼ Animal Model
Nandadasa et al. (2019) found that loss of Adamts9 and Adamts20 in mouse embryos resulted in severe developmental defects with impaired ciliogenesis and Shh (600725) signaling. Mutant mouse embryos displayed abnormal ECM dynamics in neural tubes.In yolk sac, where Adamts20 is not expressed, loss of Adamts9 alone resulted in defective angiogenesis, cilia, Hh signaling, and abnormal ECM. Analysis in ADAMTS9-null RPE1 cells demonstrated that ciliogenesis defects were independent of Shh signaling and cleavage of versican.