Table 1.
Human ADAM Family Members, Gene Locus, Molecular Weight, Tissue Distribution, and Substrates.
| ADAM | Other name | Gene Locus | MW (kDa) | Tissue Distribution | Substrate/Target | Biological or Pathological Role | Ref |
|---|---|---|---|---|---|---|---|
| 1 | Fertilin α, PH-30 α. | 12q24.12 | 84 | Nonfunctional pseudogene, testis | TBD | Sperm form complex, sperm-egg interaction. | [27] |
| 2 | Fertilin β, PH-30 β, Cancer/testis antigen 15 | 8p11.22 | 100 | Testis, epididymis | TBD | Sperm form complex, sperm-egg interaction. | [27] |
| 3 | Cyritestin, tMDC I | 8p11.22 | 80 | Testis, epididymis | TBD | Sperm form complex | [27] |
| 6 | tMDC IV | 14q32.33 | 60 | Testis | TBD | Sperm form complex | [27] |
| 7 | EAP-1, Sperm maturation-related glycoprotein GP-83 | 8p21.2 | 84 | Reproductive system, epididymis, testis | TBD | Transmembrane protein. | [27] |
| 8 | Cell surface antigen MS2, CD156a | 10q26.3 | 90 | Human neutrophils | CHL-1, PSGL-1, CD23, CD-30-ligand, ADAM8 pro-domain, APP, L-selectin, MBP | Osteoclast differentiation, rheumatoid arthritis, neutrophil rolling, trans-endothelial extravasation, neurodegeneration | [62–64] |
| 9 | MDC9, Meltrin γ Myeloma cell metalloprotease | 8p11.22 | 91 | Muscle cell, brain | Pro-HB-EGF, APP, fibronectin, gelatin, Angiotensin-I converting enzyme (ACE), laminin, insulin-B chain, collagen XVII, delta-like ligand 1, EGF, FGFR2IIIb, insulin-like growth factor binding protein-5 | Myogenesis, formation of myotubes; participate in endocardial cushion development (overlap with ADAM-19) | [168] |
| 10 | Kuzbanian protein homologue, CD156c | 15q21.3 | 84 | Embryonic fibroblast, endothelial cells, cardiomyocytes | Pro-HB-EGF, pro-TNFα, Notch, ephrin-α2, APP, cellular prion precursor, gelatin, DDR-1, β-cellulin, CD23, CD30, CD44, prion protein, collagen IV and XVII, fractalkine, delta-like ligand 1, desmoglein, E-cadherin, N-cadherin, VE-cadherin, EGF, ephrin A2 and A5, ERBB2, Fas-L, IL-6R, Klotho, LAG-3, L1, MICA, Pcdh-γ | Increased in dilated cardiomyopathy, atrial fibrillation. Deficiency causes embryonic lethality | [67, 68] |
| 11 | MDC | 17q21.31 | 83 | Nervous system, brain | TBD | TBD | [69] |
| 12 | Meltrin α | 10q26.2 | 100 | Placenta | IGFBP-3 & 5, pro-HB-EGF, EGF, betacellulin, Delta-like1, p-LAP, fibronectin, gelatin, collagen IV | VSMC proliferation, hypertrophic cardiomyopathy. Inhibition prevents cardiac hypertrophy, Down syndrome | [73, 74, 169] |
| 15 | Metargidin, MDC-15 | 1q21.3 | 93 | Cardiomyocyte, endothelial cell. | collage IV, gelatin, amphiregulin, CD23, E-cadherin, HB-EGF, ADAM10 | Inflammation. Contributes to pathological retina neovascularization. Increased in dilated cardiomyopathy, and in atrial fibrillation. |
[81, 170] |
| 17 | TACE, CD156b, Snake venom-like protease | 2p25.1 | 110 | Embryonic fibroblast, cardiomyocyte, smooth muscle | ECM, collagen, pro-TNF-α, pro-TGF-α, proHB-EGF, pro-amphiregulin, TRANCE, pro-neuregulin-a-2C, Notch, Fas ligand, fractalkine, L-selectin, collagen XVII, TNF receptor I and II, interleukin-1 receptor II, interleukin-6 receptor, Erb-B4/HER4, macrophage colony-stimulating factor receptor I, nerve growth factor receptor (TrkA), growth hormone receptor MUC1, APP, cellular prion precursor. | Cardiomyocyte-specific knockout exacerbates post-MI left ventricle dilation and dysfunction due to reduced angiogenesis. ADAM-17 deficient mice die perinatally due to multiple defects including thickened and mis-shaped semilunar and atrioventricular valves, and ventricular septal defect. |
[101, 102] |
| 18 | tMDC III, ADAM-27 | 8p11.22 | 79 | Testis, sperm surface protein | TBD | Highly expressed in conotruncus and endocardial cushion. | [27] |
| 19 | Meltrin β, MADDAM, Metalloprotease and disintegrin dendritic antigen marker | 5q33.3 | 105 | Peripheral nervous system, skeletal muscle, bone, heart | Pro-HB-EGF, ErbB ligands, NGR-β1 and β4, neuregulin, TNF-α, ADAM-19 | ADAM19−/− mice show defects in ventricular septum formation, immature valves, neuronal defects, and die soon after birth. | [105, 171] |
| 20 | NG | 14q24.2 | 83 | Testis specific | TBD | Embryo development | (21) |
| 21 | ADAM-31 | 14q24.2 | 85 | Testis specific | TBD | Present in mature sperm | (21, 22) |
| 22 | MDC2 | 7q21.12 | 100 | Reproductive system, brain | TBD | Expressed in both testicular somatic and germ cell | (21, 23) |
| 28 | MDC-L, ADAM-23 | 8p21.2 | 87 | Reproductive system, brain | TBD | Present in mature sperm | (21) |
| 29 | Cancer/testis antigen 73 | 4q34.1 | 127 | Testis | TBD | Present in mature sperm | (21, 25) |
| 30 | NG | 1p12 | 55 | Testis | TBD | Embryo development | [27] |
| 32 | NG | 8p11.22 | 88 | Testis | TBD | Embryo development | [27] |
| 33 | NG | 20p13 | 87 | Reproductive system | TBD | Embryo development asthma | [27] |
IGFBP-3, insulin growth factor binding protein-3; MW, molecular weight; TBD, to be determined