Disease relevance of ADAM19

• In brain tumor tissue, ADAM8 and ADAM19 undergo activation by prodomain removal resulting in active proteases [1].
• ADAM19 in proximal tubules and in peritubular capillaries was associated with interstitial fibrosis (P<0.05) [2].
• To determine whether ADAM19 is specifically related to CAN, we studied transplant biopsies with and without CAN, acute rejection and non-transplant-related kidney diseases: interstitial fibrosis (IF), interstitial atrophy, glomerular fibrosis and interstitial inflammation [3].

Psychiatry related information on ADAM19

• ADAM19 is tightly associated with constitutive Alzheimer's disease APP alpha-secretase in A172 cells [4].

High impact information on ADAM19

• Essential role for ADAM19 in cardiovascular morphogenesis [5].
• These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects [5].
• ADAM19 is also highly expressed in osteoblast-like cells in the bone, yet it does not appear to be essential for bone growth and skeletal development [5].
• In contrast, MADDAM expression was maintained in MOs differentiated along the dendritic cell (DC) pathway and induced in CD34(+)-derived DCs [6].
• Long-term culture (more than 20 hours) of MOs during macrophage (MAC) differentiation led to a rapid and complete down-regulation of MADDAM expression [6].

Biological context of ADAM19

• Human ADAM19 zymogen contains two potential furin recognition sites (RX(K/R)R), (196)KRPR(200)R and (199)RRMK(203)R, between its pro- and catalytic domains [7].
• Human ADAM19/adamalysin-19 (A disintegrin and metalloproteinase 19) was identified from primary dendritic cell cDNA libraries [8].
• To verify that endogenous ADAM19 has an APP alpha-secretase activity, we examined whether the constitutive level of alpha-secretase activity was reduced by RNA interference with ADAM19 in A172 cells [4].
• Upregulation of ADAM19 in chronic allograft nephropathy [3].
• Preliminary studies showed that a protein kinase C activator, phorbol 12-myristate 13-acetate, promoted the cellular processing of hADAM19; however, three calmodulin antagonists, trifluoperazine, W7, and calmidazolium, impaired this cleavage, indicating complex signal pathways may be involved in the processing [9].

Anatomical context of ADAM19

• Adamalysin 19 (a disintegrin and metalloproteinase 19, ADAM19, or meltrin beta) is a plasma membrane metalloproteinase [7].
• Meltrin beta/ADAM19 is a member of ADAMs (a disintegrin and metalloproteases), which are a family of membrane-anchored glycoproteins that play important roles in fertilization, myoblast fusion, neurogenesis, and proteolytic processing of several membrane-anchored proteins [10].
• Human ADAM19 (MADDAM) is a molecular marker for human dendritic cells and not expressed in macrophages [11].
• The ADAM8 and ADAM19 proteins were mainly located in tumor cells and in some tumors in endothelia of blood vessels [1].
• Normal human kidneys showed constitutive ADAM19 expression in distal tubules and endothelial cells, whereas proximal tubules were negative [2].

Associations of ADAM19 with chemical compounds

• In-situ hybridization confirmed that the ADAM19 mRNA was located in the luminal and glandular epithelium on day 12 of pregnancy [12].
• Reagents that block furin-mediated activation of pro-hADAM19, decRVKR-CMK, and brefeldin A abrogated this processing [9].
• Both Pittsburgh mutant of alpha(1)-proteinase inhibitor and dec-Arg-Val-Lys-Arg-chloromethyl ketone, two specific furin inhibitors, blocked the activation of hADAM19 [7].
• The cysteine-rich domain likely forms disulfide bonds to regulate the autolytic processing and shedding of hADAM19 [13].
• Ilomastat/GM6001 inhibited hADAM19 with an IC50 of 447 nM, but scarcely affected the shedding process [13].

Regulatory relationships of ADAM19

• This report is the first thorough investigation of the intracellular activation of adamalysin 19, demonstrating that furin activated pro-hADAM19 in the secretory pathway via one of the two consecutive furin recognition sites [7].

Other interactions of ADAM19

• The human protein shows homology with Xenopus ADAM13 (44%), human ADAM19 (40%), and human ADAM12 (39%) [14].
• ArgBP1 may be the key protein, which accounts for the physiological function of ADAM19 [15].
• Anti-metalloproteinase and anti-disintegrin domain IgG molecules inhibited the alpha-2-macroglobulin cleavage by hADAM19; however, their pre-immune and anti-pro-domain IgG molecules did not [16].
• These data suggest that the ADAM19 may be involved in the key processes of glandular secretion, trophoblast invasion and degradation of extracellular matrix during early pregnancy [12].

Analytical, diagnostic and therapeutic context of ADAM19

• RNA in situ hybridization revealed widespread ADAM19 mRNA expression in the nephrogenic zone of human fetal kidneys [2].
• Although these observational data do not establish a cause and effect relationship, ADAM19 may have a modulatory role in the dysfunctional renal allograft state [3].
• Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.002) [3].
• We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys [3].
• Northern blot analysis confirmed this result and revealed a signal of MADDAM messenger RNA (mRNA) at about 7.5 kilobases (kb) [6].

References