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Official Full Name
ADAM metallopeptidase with thrombospondin type 1 motif, 1
This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) 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 contains two disintegrin loops and three C-terminal TS motifs and has anti-angiogenic activity. The expression of this gene may be associated with various inflammatory processes as well as development of cancer cachexia. This gene is likely to be necessary for normal growth, fertility, and organ morphology and function. [provided by RefSeq, Jul 2008]
ADAMTS1; ADAM metallopeptidase with thrombospondin type 1 motif, 1; C3-C5; METH1; A disintegrin and metalloproteinase with thrombospondin motifs 1; METH-1; ADAM-TS1; ADAMTS-1; ADAM-TS 1; human metalloproteinase with thrombospondin type 1 motifs; a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1; a disintegrin like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1; C3 C5; KIAA1346

A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS-1) is Kun's first member of the ADAMTS metalloproteinase family found in the study of mouse colon adenocarcinoma cell lines in 1997. The human ADAMTS-1 gene is located on the human chromosome 21q21-q22 and encodes a protein of 951 amino acids with a molecular weight of approximately 100 kD.

ADAMTS-1 includes six domains: pre-metalloproteinase, metalloproteinase, a disintegrin-like domain, thrombospondin homologous domain containing TSP-1, spacer and C-terminal thrombin-sensitive protein (TSP) domain, belonging to Zn2+-dependent secreted metalloproteinase, which can be synthesized and secreted by various cells such as macrophages, vascular endothelial cells, smooth muscle cells, and fibroblasts. During the secretion process, the inactive ADAMTS-1 precursor was cleaved into two active forms, 87 kD, and 65 kD, in two successive steps. After ADAMTS-1 is secreted, it is mostly anchored in the extracellular matrix through three TSP repeats and spacers at the C-terminus.

ADAMTS-1 is more widely expressed in mammals. In human normal tissues and organs, the expression level is relatively low, and the tissues with relatively high expression levels are heart, lung, adipose tissue, liver, kidney, brain and skeletal muscle. In growth and development, genitourinary organs formation, ovarian ovulation, follicles. And ADAMTS-1 plays an important role in atherosclerosis (AS), viral myocarditis, and tumors.

Biological Function of ADAMTS-1

The expression of ADAMTS-1 is affected by many factors, among which many inflammatory factors are important factors affecting its expression. For example, inflammatory factors such as TNF-α, IL-1β, and endotoxin can induce the expression of ADAMTS-1. The transforming growth factor TGF-β down-regulates its expression. Various hormones in the body such as androgen, estrogen, progesterone, chorionic gonadotropin and parathyroid hormone can regulate their expression. At the same time, ADAMTS-1 can be involved in the regulation of inflammation by up-regulating the expression of inflammatory factors by inflammatory factors that are secreted by immune cells.

ADAMTS-1 blocks the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) by binding to the heparin-binding domain of vascular endothelial growth factor (VEGF)-165 at the C-terminus, thereby inhibiting endothelial cell proliferation and angiogenesis. In addition, ADAMTS-1 can also inhibit angiogenesis by activating the matrix glycoproteins TSP-1 and TSP-2, which have anti-angiogenic effects. Martino-Echarri et al. also found that ADAMTS-1 is responsible for the degradation of nidogen-1 and -2 in a mouse model of breast cancer, which helps to enhance the anti-angiogenic response of metalloproteinases. Inagaki et al. found that ADAMTS-1 can block the phosphorylation of VEGFR3 in human dermal lymphatic microvascular endothelial cells HMVEC-dLy, thereby inhibiting lymphangiogenesis.

Chen et al. showed that Adamts1 mainly involves the fat cell lineage stereotype and contributes to the development of obesity. ADAMTS-1 impairs fat cell lineage typing by ECM remodeling by activating the FAK-ERK signaling pathway. In addition, miR-181d up-regulated by BMP4 dominates the Adamts1-ECM-FAK-ERK axis during fat cell lineage typing.

Figure 1. Model of Adamts1-mediated impairment of MSCs adipocyte commitment. (Chen, S. Z. et al. 2016)

ADAMTS-1 and Atherosclerosis

It was found in rat experiments that ADAMTS-1 up-regulated the expression of E-selectin. The establishment of mouse carotid blood flow interruption model also found that ApoE knockout ADAMTS-1 transgenic mice were significantly thicker than the arterial intima of ApoE knockout mice. Therefore, ADAMTS-1 may participate in the occurrence and development of atherosclerosis by degrading versican in the extracellular matrix and promoting the migration of vascular smooth muscle cells.

ADAMTS-1 is a pluripotent enzyme, and immunohistochemical staining of human atherosclerotic plaques revealed high expression of ADAMTS-1. Further studies have shown that ADAMTS-1 can hydrolyze glutamate-alanine bonds in versican, degrade endomembrane matrix proteins, and make VSMCs more likely to invade the inner membrane. At the same time, ADAMTS-1 can also bind to VEGF, block the phosphorylation of VEGFR2, and inhibit the proliferation of endothelial cells.

Therefore, ADAMTS-1 may promote the migration of VSMCs, inhibit the proliferation of endothelial cells, regulate the inflammatory response, initiate and accelerate the occurrence and development of atherosclerosis by degrading polyproteins in the extracellular matrix.

ADAMTS-1 and Coronary Heart Disease

Studies have shown that ADAMTS-1 has a close relationship with various types of coronary heart disease. ADAMTS-1 promotes the formation and progression of atherosclerotic plaques, causing coronary stenosis, resulting in reduced oxygen supply to the coronary arteries. When the coronary blood supply can’t meet the needs of myocardial metabolism, causing acute and temporary ischemia and hypoxia of the myocardium, angina can occur.

It was found through experiments that the expression of ADAMTS-1 mRNA was extremely weak in normal myocardial tissue, but it increased significantly in the early stage of acute myocardial infarction, and its expression increased earlier than MMPs that have been shown to play an important role in ventricular remodeling after myocardial infarction mRNA, and thus Nakamura et al. proposed that ADAMTS-1 plays an important role in ventricular remodeling after acute myocardial infarction and participates in the occurrence and development of ischemic cardiomyopathy.

Hirohata et al. found that hypoxia-induced endothelial cells have the ADAMTS-1 expression, and serum ADAMTS-1 levels are elevated in patients with acute myocardial infarction. Once the arteries are reperfused, serum ADAMTS-1 levels rapidly return to normal levels. ADAMTS-1 may have a unique role in the tumor microenvironment. The study analyzed ADAMTS-1-deficient mice and showed that ADAMTS-1 has a variety of biological functions.

ADAMTS-1 and Cancer

When human fibrosarcoma HT-1080, human prostate cancer DU-145 and Chinese hamster ovary CHO-K1 cells were inoculated subcutaneously in mice, ADAMTS-1 inhibited tumor growth. Studies have shown that overexpression of ADAMTS-1 in a fibrosarcoma model increases angiogenesis-independent tumor growth rates. Furthermore, in contrast to the vasopressor produced by proteolytic cleavage of thrombospondin-1, the enzymatic activity of ADAMTS-1 is required to enhance angiogenesis and promote lung metastasis of Lewis lung cancer and TA3 mouse breast cancer cells.

ADAMTS-1 proteolytic activity can be increased by interaction with fibulin-1, a secretory glycoprotein that also shows tumor and anti-tumor effects. In turn, fibulin-1 can interact with different extracellular matrix components, including known ADAMTS-1 substrates such as nidogen-1 and versican. Tan et al. have shown that fibulin-1 plays a crucial role in the balance of tumor protection and tumor protection function exhibited by ADAMTS-1. In each case, these studies support the effect of ADAMTS-1 catalytic activity on tumor microenvironment remodeling to promote the spread of tumor cells in different types of cancer.

Silva et al. found that immunofluorescence showed colocalization of ADAMTS-1 and nuclear phosphoprotein in MCF-10A, MCF-7 and MDA-MB-231 cell lines. It is indicated that ADAMTS-1 is expressed in the nucleus and nucleolus of three breast cell lines, and the expression level is more abundant than that observed in the cytoplasm.


  1. Silva, S. V., Lima, M. A., Nathalie, C., Jaeger, R. G., & Freitas, V. M. (2016). Adamts-1 is found in the nuclei of normal and tumoral breast cells. Plos One, 11(10).
  2. Hirohata, S., Inagaki, J., & Ohtsuki, T. (2017). Diverse functions of a disintegrin and metalloproteinase with thrombospondin motif-1. Yakugaku Zasshi-journal of the Pharmaceutical Society of Japan, 137(7), 811-814.
  3. Chen, S. Z., Ning, L. F., Xu, X., Jiang, W. Y., Xing, C., & Jia, W. P., et al. (2016). The mir-181d-regulated metalloproteinase adamts1 enzymatically impairs adipogenesis via ecm remodeling. Cell Death & Differentiation, 23(11).
  4. Martino-Echarri E, Fernandez-Rodriguez R, Rodriguez-BaenaFJ, Barrientos-Duran A, Torres-Collado AX, Plaza-Calonge Mdel C, et al.(2013). Contribution of ADAMTS1 as a tumor suppressorgene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2.Int J Cancer, 133:2315–24.
  5. Inagaki J, Takahashi K, Ogawa H, Asano K, Faruk Hatipoglu O, Cilek MZ, et al.(2014). ADAMTS1 inhibits lymphangiogenesis by attenuating phosphorylation of the lymphatic endothelial cellspecific VEGF receptor. Exp Cell Res, 323:263–75.
  6. Tan Ide A, Ricciardelli C, Russell DL. (2013).The metalloproteinase ADAMTS1: a comprehensive review of its role in tumorigenic and metastatic pathways. Int J Cancer, 133:2263–76.