A disintegrin and metalloproteinase with thrombospondin motifs 3 is an enzyme that in humans is encoded by the ADAMTS3gene.[5][6] The protein encoded by this gene is the major procollagen II N-propeptidase.[6]
Structure
This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene is the major procollagen II N-propeptidase.[6]
Function
Because of the high similarity to ADAMTS2, the major substrate of ADAMTS3 had been erroneously assumed to be procollagen II.[7] However, ADAMTS3 appears largely irrelevant for collagen maturation but instead is required for the activation of the lymphangiogenic growth factor VEGF-C.[8] Hence, ADAMTS3 is essential for the development and growth of lymphatic vessels. The proteolytic processing of VEGF-C by ADAMTS3 is regulated by the CCBE1 protein.
ADAMTS3 has been shown to cleave reelin, a protein that regulates the proper lamination of the brain cortex and whose signal activity is found to be disrupted in a number of neuropsychiatric conditions.[9]
Clinical significance
A deficiency of this protein may be responsible for dermatosparaxis, a genetic defect of connective tissues.[6]
Some hereditary forms of lymphedema are caused by mutations in ADAMTS3.[10][11]
Tang BL (January 2001). "ADAMTS: a novel family of extracellular matrix proteases". The International Journal of Biochemistry & Cell Biology. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID11167130.
Martel-Pelletier J, Welsch DJ, Pelletier JP (December 2001). "Metalloproteases and inhibitors in arthritic diseases". Best Practice & Research. Clinical Rheumatology. 15 (5): 805–29. doi:10.1053/berh.2001.0195. PMID11812023.
Hirohata S (November 2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku. The Journal of Japanese Biochemical Society. 73 (11): 1333–7. PMID11831030.
