Table 2.

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

ADAMTS	Gene Locus	MW (kDa)	Tissue Distribution	Target/Substrate	Implications in Biology or Disease	Ref
1 METH1	21q21.3	105	Heart, aorta, smooth muscle, bronchial epithelial cells, fetal lung, liver, colon, kidney, adrenal gland, bladder, prostate, ovary, uterus, placenta, spinal cord, ciliary ganglion, olfactory bulb, adipocytes, breast stromal fibroblasts, myoepithelial cells	Aggrecan, versican, syndecan 4, dystroglycan, mac-2, gelatin (denatured collagen type I), amphiregulin, TGF-α, HB-EGF, VEGF, TFPI-2, semaphorin 3C, nidogen-1 & −2, desmocollin-3	Embryogenesis. organ development, VSMC proliferation, inflammation, Anti-angiogenic, cancer cachexia, gastric cancer & lymph node metastasis, lung cancer	(J. Chen, et al., 2013; Gunther, et al., 2005; Kelwick, Desanlis, Wheeler, & Edwards, 2015; Kilic, et al., 2017; Kuno, et al., 1997; Y. Qu & Zhang, 2018; J. H. Tang, et al., 2017; Toba, et al., 2016; Vazquez, et al., 1999)
2	5q35.3	135	Aorta, smooth muscle, heart, lung, liver, kidney, bladder, skeletal muscle, tendon, bone, skin, retina, superior cervical ganglion, breast stromal fibroblasts adipocytes, uterus, placenta	Fibrillar procollagen type I, II, III & V, N-propeptide	Anti-angiogenic, cartilage matrix anabolism, procollagen N-proteinase, osteoarthritis, Ehlers-Danlos syndrome type VIIc	(Bekhouche & Colige, 2015; Colige, et al., 1997; Dubail, et al., 2010; Kelwick, Desanlis, et al., 2015)
3	4q13.3	136	CD105+ ECs, CD34+ cells, heart, lung, pineal gland, cartilage, bone, skeletal muscle, tendon, breast myoepithelial cells, testis, ovary, placenta, brain	Fibrillar procollagen type II N-propeptide, biglycan, pro-VEGF-C, reelin	Procollagen N-proteinase, angiogenesis, lymphangiogenesis, placental & brain functions, cartilage matrix anabolism, osteoarthritis	(Bekhouche & Colige, 2015; Fernandes, et al., 2001; Janssen, et al., 2016; Jeltsch, et al., 2014; Jha, et al., 2017; Kelwick, Desanlis, et al., 2015; Ogino, et al., 2017)
4 Aggrecanase-1, ADMP-1	1q23.3	90	Ovary, adrenal cortex, ciliary ganglion, trigeminal ganglion, brain, spinal cord, retina, heart, fetal lung, appendix, gall bladder, pancreas islets, skeletal muscle, uterus, breast myoepithelial cells, synovial fluid	Aggrecan, versican, neurocan, reelin, biglycan, brevican, matrilin-3, α2-macroglobulin, COMP	VSMC apoptosis, vascular inflammation, matrix degradation, sporadic aortic aneurysm and dissections, osteoarthritis	(Boerboom, et al., 2011; Dubail & Apte, 2015; Kelwick, Desanlis, et al., 2015; P. Ren, et al., 2017)
5 ADAMTS11, Aggrecanase-2, ADMP-2	21q21.3	102	Ovary, uterus, placenta, breast myoepithelial cells, bladder, adipocytes	Aggrecan, versican, reelin, biglycan, matrilin-4, brevican, α2-macroglobulin	Osteoarthritis, cancer (anti-tumorigenic, anti-angiogenic)	(Abbaszade, et al., 1999; Dubail & Apte, 2015; Hurskainen, Hirohata, Seldin, & Apte, 1999; Kelwick, Desanlis, et al., 2015)
6	5q12.3	125	Heart, appendix, gall bladder, superior cervical ganglion, trigeminal ganglion, breast myoepithelial cells, placenta	Fibrillin-1, LTBP1, syndecan 4	Altered ventricular conduction, prolonged QRS interval	(Hurskainen, et al., 1999; Karoulias, Taye, Stanley, & Hubmacher, 2020; Kelwick, Desanlis, et al., 2015; Prins, et al., 2018)
7	15q25.1	182	Heart, smooth muscle, liver, pancreas, kidney, adrenal cortex, skeletal muscle, intervertebral disc, trigeminal ganglion, uterus, breast stromal fibroblasts	COMP, TSP-1	Atherosclerosis, CAD, VSMC migration, neointima formation, cartilage catabolism, osteoarthritis	(Hanby & Zheng, 2013; Hurskainen, et al., 1999; Kelwick, Desanlis, et al., 2015; L. Wang, et al., 2009)
8 METH2	11q24.3	96	Skeletal muscle, heart, lung, appendix, liver, adrenal cortex, breast stromal fibroblasts and luminal epithelial cells, placenta, brain, superior cervical ganglion	Aggrecan	Anti-angiogenic	(Georgiadis, Hirohata, Seldin, & Apte, 1999; Kelwick, Desanlis, et al., 2015; Vazquez, et al., 1999)
9	3p14.1	217	Capillary ECs, heart, lung, kidney, pancreas, colon, ovary, skeletal muscle, dorsal root ganglion, breast myoepithelial cells, uterus, placenta	Aggrecan, versican	Cancer	(Desanlis, Felstead, Edwards, & Wheeler, 2018; Kelwick, Desanlis, et al., 2015; Koo, et al., 2010; Somerville, et al., 2003)
10	19p13.2	121	Heart, lung, liver, pancreas, kidney, brain, adipose tissue, CD8+ T-cells, breast stromal fibroblasts, uterus, placenta	Fibrillin-1	Weill-Marchesani syndrome (short stature, acromelic dysplasia, disproportionate distal limb shortening)	(Hubmacher & Apte, 2015; Kelwick, Desanlis, et al., 2015; Kutz, et al., 2011; Le Goff & Cormier-Daire, 2009; Mead & Apte, 2018; Somerville, Jungers, & Apte, 2004)
12	5p13.3	178	Atrioventricular node, smooth muscle, liver, gall bladder, bone marrow, adipose tissue, intervertebral disc, breast stromal fibroblasts and myoepithelial cells	COMP	Anti-angiogenic. Cell adhesion, cancer, osteoarthritis	(Bai, Wang, Luan, Yu, & Liu, 2009; El Hour, et al., 2010; Kelwick, Desanlis, et al., 2015)
13	9q34.2	154	ECs, heart, lung, liver, hepatic stellate cells, pancreas, kidney podocytes, brain, testis, breast myoepithelial cells, placenta, CD71+ early erythroid cells, thyroid	von Willebrand factor (vWF)	Deficiency leads to thrombotic thrombocytopenic purpura (TTP)	(Cal, et al., 2002; Kelwick, Desanlis, et al., 2015; Lopez & Dong, 2004; Mead & Apte, 2018; Moake, 2004; X. Zheng, et al., 2001; X. L. Zheng, 2015)
14	10q22.1	134	Fibroblasts, lung, liver, gall bladder, prostate, retina, cerebellum, thalamus, fetal thyroid, adipocytes, bone marrow, skin, breast myoepithelial and luminal epithelial cells, placenta	Fibrillar procollagen type I N-propeptide (pNα1 and pNα2 chains)	Procollagen N-proteinase, cartilage matrix anabolism, osteoarthritis, multiple sclerosis	(Bekhouche & Colige, 2015; Cal, et al., 2002; Goertsches, Comabella, Navarro, Perkal, & Montalban, 2005; Kelwick, Desanlis, et al., 2015; Poonpet, Honsawek, Tammachote, Kanitnate, & Tammachote, 2013; Rodriguez-Lopez, et al., 2009)
15	11q24.3	103	Heart, colon, brain, musculoskeletal system, adipose tissue, breast myoepithelial cells, uterus, placenta	Aggrecan, versican	Anti-angiogenic, anti-tumorigenic	(Dancevic, et al., 2013; Kelwick, Desanlis, et al., 2015)
16	5p15.32	136	Aorta, gall bladder, brain, ovary, breast myoepithelial cells	ECM proteins, latency-associated peptide (LAP)-TGF-β complex	Hypertension, cardiac fibrosis and hypertrophy, heart failure. Loss linked to congenital undescended testes	(Cal, et al., 2002; Kelwick, Desanlis, et al., 2015; Sarila, et al., 2020; Yao, et al., 2020)
17	15q26.3	121	Ovary, breast myoepithelial cells	Fibrillin-1 & −2, fibronectin	Weill-Marchesani-like syndrome	(Cal, et al., 2002; Hubmacher & Apte, 2015; Karoulias, et al., 2020; Kelwick, Desanlis, et al., 2015; Mead & Apte, 2018)
18	16q23.1	135	Endothelium, heart, brain, ciliary ganglion, skin, prostate, breast myoepithelial cells, uterus, placenta	Basal membrane-specific proteoglycan Col18a1, fibronectin	Microcornea, myopic chorioretinal atrophy and telecanthus	(Ataca, et al., 2020; Cal, et al., 2002; Dubail & Apte, 2015; Kelwick, Desanlis, et al., 2015; Mead & Apte, 2018; R. Zhu, et al., 2018)
19	5q23.3	134	Dorsal root ganglion, breast myoepithelial cells, uterus, placenta	ECM Proteins	Loss causes non-syndromic heart valve disease	(Karoulias, et al., 2020; Kelwick, Desanlis, et al., 2015; Wunnemann, et al., 2020)
20	12q12	215	Heart, lung, appendix, liver, pancreas, brain, skeletal muscle, pituitary, trigeminal ganglion, prostate, testis, breast myoepithelial cells, ovary, placenta	Versican	Colorectal, brain and breast cancer. Cleft lip and palate	(Kelwick, Desanlis, et al., 2015; Llamazares, Cal, Quesada, & Lopez-Otin, 2003; Somerville, et al., 2003; Z. T. Wolf, et al., 2015)