Table 1.

Human ADAM Family Members, Gene Locus, Molecular Weight (MW) of Full-length Protein, Source/Tissue Distribution, Targets/Substrates, and Implications in Biology or Disease

ADAM Other Name	Gene Locus	MW kDa	Source/Tissue Distribution	Target/Substrate	Implications in Biology or Disease	Ref
1 (a & b) Fertilin α, PH-30α	12q24.12	84	Sperm head surface, testis, epididymis, vas deferens	Integrins, ADAM3	Spermatogenesis, sperm maturation, sperm-egg interaction	(Cho, 2012)
2 Fertilin β, PH-30β, Cancer/testis antigen 15	8p11.22	82	Sperm head, surface, testis, epididymis, vas deferens	Integrin α6β1, epididymal protein DE (CRISP-1), intracellular chaperone calnexin, oocyte CD9, ADAM3	Sperm maturation & migration in female reproductive tract, sperm-egg interaction	(Cho, 2012)
3 Cyritestin, sperm surface antigen tMDC I, CYRN	8p11.22	80	Sperm surface, testis, epididymis	Integrins, testis-expressed gene 101, epididymal protein DE (CRISP-1), chaperones calnexin & calreticulin	Sperm maturation, sperm migration, sperm-egg interaction	(Cho, 2012)
6 Testis-derived tMDC IV	14q32.33	60	Testis	Integrins	Sperm maturation, sperm-egg interaction	(Cho, 2012)
7 EAPI, Sperm maturation-related glycoprotein GP-83	8p21.2	86	Sperm plasma membrane, testis, epididymis	Integrin α4β1 & α9β1, intracellular chaperone calnexin, heat shock protein 5, integral membrane protein 2B	Sperm maturation, sperm-egg interaction, melanoma progression	(Cho, 2012)
8 Cell surface antigen MS2, CD156a	10q26.3	90	Lung epithelium, ECs, SMCs, immune B cells, eosinophils, neutrophils, monocytes, macrophages, dendritic cells, invasive HLA-G- trophoblasts, intervertebral discs, joints, osteoclasts, neurons	Integrin β1, neural cell adhesion molecule close homologue of L1 (CHL-1), L-selectin, P-selectin glycoprotein ligand (PSGL-1), low-affinity IgE receptor CD23, low-affinity receptor FcεRII, CD-30-ligand, amyloid precursor protein (APP), fibronectin, myelin basic protein (MBP), brevican, vitronectin, VCAM-1, ADAM17	Angiogenesis, cell adhesion, neutrophil rolling, trans-endothelial extravasation, atherosclerosis, CAD, MI, ascending aortic dissection, ovulation, placental development, trophoblast migration, allergy, asthma, chronic obstructive pulmonary disease neurodegeneration, neuroinflammation, neoplastic meningitis, osteoclast differentiation, rheumatoid arthritis, breast, gastric, pancreatic, colorectal & brain cancer	(Hsia, et al., 2019; Kelly, et al., 2005; Klein & Bischoff, 2011; Le, et al., 2018; Levula, et al., 2011; Polverino, et al., 2018; Schick, et al., 2019; Vuohelainen, et al., 2011)
9 MDC9, Meltrin-γ, γ Myeloma cell metalloprotease	8p11.22	91	Lung epithelium, muscle, brain, neutrophils, monocytes, macrophages	Pro-heparin-binding EGF-like growth factor (Pro-HB-EGF), EGF, FGFR2IIIb, VEGF, integrin αvβ3, α6β1 & α9β1, APP, fibronectin, tenascin, vitronectin, gelatin, collagen XVII, ACE, laminin, delta-like ligand 1, insulin-B chain, insulin-like growth factor binding protein-5, IL-11R	α-secretase, angiogenesis, retinal neovascularization, endocardial cushion development, myogenesis, formation of myotubes, wound healing, bone formation, fertilization, cell proliferation & /migration, cell-cell interactions, AAA, lung inflammation, chronic obstructive pulmonary disease, chondrocyte differentiation and proliferation, osteoarthritis, gastric pancreatic, colorectal and ovarian carcer. Decreased in anterior polar cataract	(Hodgkinson, et al., 2010; Horiuchi, Zhou, Kelly, Manova, & Blobel, 2005; Roychaudhuri, et al., 2014; G. Shen, et al., 2020)
10 Kuzbanian protein homologue, CD156c, MDAM	15q21.3	84	Embryonic fibroblast, ECs, SMCs, cardiomyocytes, blood eosinophils, monocytes, macrophages, lung epithelium	Pro-HB-EGF, pro-TNFα, Notch, APP, cellular prion precursor, gelatin, DDR-1, β-cellulin, CD23, CD30, CD44, collagen IV & XVII, fractalkine, delta-like ligand 1, desmoglein, E-cadherin, N-cadherin, VE-cadherin, EGF, ephrin-A2 & A5, ErbB2 ligands, Fas-L, IL-6R, IL-11R, IL-23R, Klotho, LAG-3, MICA, Pcdh-γ, fibronectin, cystatin C, type I & II single membrane-spanning proteins, RAGE, JAM-A, ICAM-1	α-secretase, Notch signaling, SMC proliferation, leukocyte migration, vascular cell apoptosis, wound healing, AAA, unstable atherosclerotic plaques, dilated cardiomyopathy, atrial fibrillation. acute lung inflammation, asthma, nervous system development, Alzheimer’s disease, chondrocyte proliferation & differentiation, osteoarthritis, colorectal cancer. Deficiency causes embryonic lethality	(Duru, et al., 2014; Hartmann, et al., 2002; Hodgkinson, et al., 2010; Hsia, et al., 2019; Mehta, et al., 2018; Pelisek, et al., 2012; Raucci, et al., 2008; Schulz, et al., 2008; G. Shen, et al., 2020; Speck, et al., 2015; C. Zhang, et al., 2010)
11 MDC11	17q21.31	83	Brain Hippocampus, cerebellum, brown fat	Integrin α4. Non-proteolytic	Neural development, myelination, synaptic transmission, epilepsy, breast cancer suppression. ADAM11−/− mice show learning deficiencies	(Hsia, et al., 2019; Takahashi, et al., 2006; L. Wang, et al., 2018)
12 Meltrin-α, MLTN, MLTNA	10q26.2	100	SMCs, blood monocytes, macrophages, placenta	Insulin growth factor binding protein-3 (IGFBP-3), IGFBP-5, pro-HB-EGF, integrin α9β1, EGF, betacellulin, Delta-like1, gelatin, collagen IV, placental leucine aminopeptidase (P-LAP)	SMC proliferation, unstable atherosclerotic plaques, hypertrophic cardiomyopathy, bronchial asthma, breast, bladder & colorectal cancer, chondrocyte differentiation and proliferation, osteoarthritis, Down syndrome	(Asakura, et al., 2002; Duru, et al., 2014; Kurisaki, et al., 2003; Nyren-Erickson, et al., 2013; Pelisek, et al., 2012; Smiljanic, et al., 2011)
15 Metargidin, MDC15, AD56, CR II-7	1q21.3	93	Testis, ECs, SMCs, cardiomyocytes, blood monocytes, macrophages	Acrogranin, collagen IV, gelatin, amphiregulin, CD23, E-cadherin, HB-EGF, integrins α9β1 & αvβ3, Src family protein-tyrosine kinases, CD23, ADAM10	Sperm-egg interaction, cell-cell adhesion, angiogenesis, retinal neovascularization, vascular cell apoptosis, neointima formation, wound healing, atrial fibrillation, dilated cardiomyopathy, atherosclerosis, ascending aortic dissection, inflammation, rheumatoid arthritis, meningioma	(Charrier-Hisamuddin, et al., 2008; Chung, et al., 2016; Hodgkinson, et al., 2010; Horiuchi, et al., 2003; Hou, et al., 2015; Levula, et al., 2011)
17 TACE, CD156b, Snake venom-like protease, cSVP	2p25.1	93	Embryonic fibroblasts, SMCs, cardiomyocytes, blood monocytes, macrophages, lung epithelium	ECM, collagen, pro-TNFα, pro-TGF-α, pro-HB-EGF, EGFR ligand pro-amphiregulin, ACE2, TRANCE, pro-neuregulin-a-2C, Notch, Fas ligand, fractalkine, L-selectin, collagen XVII, TNFR I & II, IL-1R II, IL-6R, IL-11R, IL-23R, Erb-B4/HER4, macrophage colony-stimulating factor receptor I, nerve growth factor receptor (TrkA), growth hormone receptor MUC1, APP, cellular prion precursor, fibronectin, cystatin C, β1 integrin, N-cadherin, VE-cadherin, JAM-A, ICAM-1, VCAM-1, syndecan-1, α-Klotho	α-secretase, TNFα processing, angiogenesis, EC and epithelial permeability, trans-endothelial leukocyte migration, SMC proliferation, vascular cell apoptosis. Wound healing, Kawasaki disease, lung inflammation, neurite outgrowth and myelination, neuroinflammation, neoplastic meningitis, gastric and colorectal cancer. Knockout mice die perinatally with thickened and mis-shaped semilunar and atrioventricular valves, ventricular septal defect. Cardiomyocyte-specific knockout show reduced angiogenesis, post-MI left ventricle dilation & dysfunction	(Bertram, et al., 2015; Caolo, et al., 2015; Fan, et al., 2016; Hodgkinson, et al., 2010; Hsia, et al., 2019; Jackson, et al., 2003; Y. Jin, et al., 2013; Mukerjee, et al., 2019; Peng, et al., 2016; Perna, et al., 2017; Rizza, et al., 2015; Sahin, et al., 2004; M. Shen, et al., 2017; Speck, et al., 2015; R. Wang, et al., 2018)
18 tMDC III, ADAM27	8p11.22	83	Testis, sperm surface protein	Conotruncus (superior end of bulbus cordis of heart)	Endocardial cushion and heart development	(Cho, 2012)
19 Adamalysin19, Meltrin-β, MADDAM, Metalloprotease and disintegrin dendritic antigen marker, FKSG34	5q33.3	105	Heart, SMCs, lung epithelium, kidney, eosinophils, brain, peripheral nervous system, skeletal muscle, bone, testis	Pro-HB-EGF, ErbB ligands, NGR-β1 & β4, neuregulin, TNFα. Constitutive α-secretase activity that promotes processing of APP and could protect against Alzheimer’s disease	Cell adhesion, cell-cell & cell-matrix interactions, embryo implantation, cardiovascular morphogenesis and neurogenesis, endocardial cushion development, endocardial epithelial-to-mesenchymal transformation, formation of cardiac septa and valves, dendritic cell differentiation. Brain astrocytoma and glioblastoma, lung, colon and ovarian cancer, lung and kidney inflammation. ADAM19−/− mice show ventricular septum defect, immature valves, neuronal defects, and die soon after birth	(Kurisaki, Masuda, Osumi, Nabeshima, & Fujisawa-Sehara, 1998; Kurohara, et al., 2004; Qi, Newcomer, & Sang, 2009; Yagami-Hiromasa, et al., 1995; H. M. Zhou, et al., 2004)
20	14q24.2	82	Testis, monocytes	Integrins	Embryo development	(Blobel, 1997)
21 ADAM31	14q24.2	81	Testis, blood monocytes, glia	Integrins	Sperm maturation, neurogenesis	(Blobel, 1997; Blobel & White, 1992)
22 MDC2	7q21.12	100	Reproductive system, brain	Brain integrins. Non-proteolytic	Neural development, myelination, synaptic transmission, epilepsy, neointima formation	(Blobel, 1997; Hsia, et al., 2019; S. M. Zhang, et al., 2019)
28 e-MDC II, MDC-L	8p21.2	87	Epididymis,brain, lymphocytes	Integrins α4β1, α4β7 & α9β1, CD23	Sperm maturation, cancer	(Blobel, 1997)
29 Cancer/testis antigen 73, svph 1	4q34.1	93	Testis	Integrin α4	Sperm maturation, melanoma progression	(Blobel, 1997; Smith, et al., 2002; L. Wang, et al., 2018)
30 svph 4	1p12	89	Sperm, testis	APP metabolism	Embryo development. Loss linked to amyloid-β deposition & Alzheimer	(Cho, 2012; Letronne, et al., 2016)
32	8p11.22	88	Sperm surface, testis, epididymis	Hyaluronic acid	Sperm development, egg fertilization	(Cho, 2012; Torabi, Bogle, Estanyol, Oliva, & Miller, 2017)
33	20p13	88	Testis,epididymis lung epithelium	Integrin α9β1	Embryo development, SMC proliferation, bronchial asthma	(Cho, 2012; Kim, et al., 2017)