A disintegrin and metalloproteinase with thrombospondin motifs 1 is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''ADAMTS1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

This gene encodes a member of the

ADAMTS ADAMTS (short for a disintegrin and metalloproteinase with thrombospondin motifs) is a family of multidomain extracellular protease enzymes. 19 members of this family have been identified in humans, the first of which, ADAMTS1, was described in 1997 ...

disintegrin Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Operation Disintegrins work by countering th ...

and

metalloproteinase A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myoge ...

with

thrombospondin Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 ...

motif) protein family. Members of the family share several distinct protein modules, including a

propeptide A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...

region, a

domain, a disintegrin-like domain, and a

type 1 (TS) motif. Individual members of this family differ in the number of

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

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. ADAMTS1 is a metalloproteinase whose structure includes several critical domains that enable its enzymatic function. These include a metalloproteinase domain, disintegrin-like domain, thrombospondin type 1 repeats (TSRs), and C-terminal regions such as spacer and cysteine-rich domains. Spacer domains are essential for substrate binding and contain clusters of positively charged residues that interact with negatively charged substrates such as versican and aggrecan. Cysteine residues contribute to the structural stability of ADAMTS1, and deletion of this domain significantly reduces versicanase activity. Thrombospondin type 1 repeats facilitate binding to sulfated glycosaminoglycans, including heparin and heparan sulfate, which helps anchor ADAMTS1 within the extracellular matrix (ECM). This positioning is important for efficient proteolytic activity on ECM substrates.

Function

ADAMTS1 plays a key enzymatic role in remodeling the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

(ECM) by cleaving proteoglycans such as

versican Versican is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the ''VCAN'' gene. Versican is a large chondroitin sulfate proteoglycan with an apparent molecular mass of more than 1000kDa. I ...

and

aggrecan Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ''ACAN'' gene. This gene is a member of the lectican ( chondroitin sulfate pr ...

. These substrates are major components of the ECM and are particularly important for cartilage development and maintaining structural integrity. By targeting specific cleavage sites, ADAMTS1 regulates ECM composition, influencing cell migration, differentiation, and tissue remodeling. This enzymatic activity is critical for several physiological processes, including fertilization, cardiovascular development, and cancer progression. Its ability to remodel ECM components is central to maintaining tissue architecture and facilitating intercellular signaling. More broadly, ADAMTS proteases contribute to ECM remodeling necessary for tissue

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

and

germ cell A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...

development in both sexes. These structural rearrangements allow for proper ligand-receptor interactions that support coordinated tissue growth and regression. During

folliculogenesis :''Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.'' In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an ...

, ADAMTS1, along with

ADAMTS4 A disintegrin and metalloproteinase with thrombospondin motifs 4 is an enzyme that in humans is encoded by the ''ADAMTS4'' gene. This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein fam ...

and ADAMTS16, is upregulated by

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH), promoting follicle growth and survival. ADAMTS1 is predominantly expressed in granulosa cells, where it is essential for follicular integrity. In its absence, granulosa cells progressively degenerate, leading to follicular breakdown. However, the oocytes remain intact and accumulate within the ovarian stroma.

Clinical significance

Expression of the ''ADAMTS1'' gene has been associated with various inflammatory processes and the development of

cancer cachexia Cachexia () is a syndrome that happens when people have certain illnesses, causing muscle loss that cannot be fully reversed with improved nutrition. It is most common in diseases like cancer, congestive heart failure, chronic obstructive pul ...

. Altered expression or activity of ADAMTS proteases, including ADAMTS1, has been linked to reproductive disorders such as

polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...

(PCOS). These disruptions may impair ECM remodeling, which is crucial for proper follicular development and ovulation, contributing to the pathophysiology of PCOS and related fertility issues.

Interactions

ADAMTS1 has been shown to interact with Vascular endothelial growth factor A.

References

External links

* The

MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibito ...