ADAMTS5 Antibodies

A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5)

Metalloproteinase that plays an significant role in connective tissue organization, development, inflammation, arthritis, and cell migration. ADAMTS5 is an extracellular matrix (ECM) degrading enzyme that reveal proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) such as aggrecan, versican, brevican and neurocan (PubMed:16133547, PubMed:18992360).

Cleavage within the hyalectans happens at Glu-Xaa recognition motifs. Plays a role in embryonic development, such as limb and cardiac morphogenesis, and skeletal muscle development through its versican remodeling properties.

Gene Information

Human
Gene Name:	ADAMTS5
Uniprot:	Q9UNA0
Entrez:	11096

Family

Belongs to:
No superfamily

Alternative Names

A disintegrin and metalloproteinase with thrombospondin motifs 11; a disintegrin-like and metalloprotease (reprolysin type) with thrombospondintype 1 motif, 5 (aggrecanase-2); ADAM metallopeptidase with thrombospondin type 1 motif, 5; ADAM-TS 11; ADAM-TS 5; ADAMTS11; ADAMTS-11; ADAMTS5; ADAM-TS5; ADAMTS-5; ADMP2; ADMP-2; ADMP-2A disintegrin and metalloproteinase with thrombospondin motifs 5; Aggrecanase 2; aggrecanase-2; disintegrin-like and metalloprotease with thrombospondin type 1 motif, 510ADAMTS11FLJ36738; EC 3.4.24; EC 3.4.24.-; EC 3.4.24.14; EC 3.4.24.82

Molecular Weight

Mass (kDA):
101.718 kDA

Genomic Context

Human
Location:	21q21.3
Sequence:	21; NC_000021.9 (26917922..26967758, complement)

Tissue Specificity

Expressed at low level in placenta primarily but also detected in heart and brain, cervix, uterus, bladder, esophagus, rib cartilage, chondroblastoma, fibrous tissue and a joint capsule from an arthritic patient.

Subcellular Localizations

Secreted, extracellular space, extracellular matrix.

Diseases

• Degenerative Polyarthritis
• Arthritis
• Abnormal Degeneration
• Osteoarthritis, Knee
• Rheumatoid Arthritis
• Intervertebral Disc Degeneration
• Inflammation
• Arthropathy
• Tumor Angiogenesis
• Malignant Neoplasms
• Neoplasms
• Chondrosarcoma

• Pain
• Hypertrophy
• Cartilage Diseases
• Tissue Adhesions
• Osteophyte
• Fibrosis
• Headache

Pathways

• Pathogenesis
• Proteolysis
• Cell Proliferation
• Localization
• Angiogenesis
• Aging
• Secretion
• Ossification
• Chondrocyte Hypertrophy
• Regeneration
• Dedifferentiation
• Cell Death
• Cell Adhesion

• Cell Migration
• Chondrocyte Proliferation
• Endochondral Ossification
• Cartilage Development
• Chondrocyte Differentiation
• Tissue Development
• Secretory Pathway

PTMs

• Cleavage
• Phosphorylation
• Methylation
• Glycosylation
• Carboxylation

• Sulphation
• Nitration
• Biotinylation
• Reduction
• C-mannosylation

Research Areas

• GPCR

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/ADAMTS5

Best Uses Of The ADAMTS5 Marker

ADAMTS5 has many uses in biological research. It's secreted in fibroblasts and has higher biological activity than its famous cousin, the ADAMTS429 that is also used in Cytology. This article will provide information about ADAMTS5 as well as its possible uses.

ADAMTS5 works more efficiently than ADAMTS429

The differences between ADAMTS4 & ADAMTS5 are largely due their different functionalities. Both ADAMTS4 & ADAMTS5 have major aggrecan degrading proteins. There is a slight overlap in enzymatic activity between these enzymes. The TS5 constituent is more active than ADAMTS429 and thus forms the catalytically active homo-oligomer.

ADAMTS5 includes the catalytic and ADAMTS429 contains the disintegrin domains. This suggests that ADAMTS5 may be a valid target for aggrecanase-inhibitors. Small-molecule inhibitors aren't as selective as monoclonal antibodies and only have one mechanism. They inhibit ADAMTS5 activity through binding to a zinc-binding protein.

Inhibiting ADAMTS5 through siRNA or microRNA was shown to delay disc development in rabbits. This suggests disc degeneration is caused by ADAMTS5. ADAMTS5 simiRNA delayed disc degeneration among NP animals, while NPs treated with ADAMTS5 simiRNA saw significant improvements in MRI, histologic, and cellular scores. ADAMTS5 could be a candidate for a future OA treatment.

Interestingly, a recent study reported that ADAMTS5 is significantly more active than ADAMTS429 in human cadaveric discs. Moreover, a recent human cadaveric study revealed the presence of aggrecanase-generated fragments in both NP and IVD tissues, and that the latter was more active than the former. ADAMTS429 was also found in NP tissues derived from discs with greater disc degradation.

Moreover, the overexpression of ADAMTS429 and ADAMTS5 is promoted by SOX4 (SOXC subgroup). The latter has also been implicated as a cause of severe OA. Despite the presence of ADAMTS429 ADAMTS5 is still more active than ADAMTS429. It also has a greater effect in OA mice than ADAMTS429.

The study demonstrates ADAMTS5 to be more active than its sibling gene, ADAMTS429 or ADAMTS4. The researchers also determined the relative expression of ADAMTS429 in GDM and preeclamptic pregnancies. The results of this study will be useful for identifying ADAMTS429 and ADAMTS5 in different cell types and in patients with GDM.

TIMP3 inhibits ADAMTS5’s aggrecanase activity within cartilage. TIMP3 is a multifunctional protein that is found in connective tissues. It plays an important role in inhibiting the MMPs. Its Nterminal inhibitory area is different from that found in ADAMTS4, the same protein that inhibits ADAMTS5. However, ADAMTS5 can be cleared from chondrocytes by lipoprotein receptor-related protein 1 (LRP-1).

ADAMTS5 responds to OA in a different way than ADAMTS4. It prevented cartilage destruction by upregulating in OA models both in vivo, and in vitro. In a mouse model for posttraumatic OA, mice lacking ADAMTS5 had a significant reduction of articular cartilage. OA was also observed in mice with Adamts4 deletion. Rats showed an increase in ADAMTS5 expression with OA progression.

It is secreted in fibroblasts

The ADAMTS proteases alter levels of versican within the pericellular matrix of fibroblasts. These studies suggest that Adamts5 might be secreted from fibroblasts. To test this hypothesis, dermal fibroblasts were isolated from mice and cultured. RNA was extracted from these fibroblasts, and relevant ADAMTS transcripts were detected using RT-PCR. Adamts5 & Adamts1 were the most abundant ADAMTS transcripts in dermal fibroblasts. Adamts4 & ADAMTS8 were found in other tissues.

This enzyme was originally implicated as a catalyst in the destruction and repair of cartilage proteoglycan acecan in arthritis. However, its physiological functions are still unknown. Adamts5 expression during embryogenesis has been confirmed by in situ hybridization with an Adamts5 cRNA probe and by immunohistochemistry. Moreover, ADAMTS5 expression was noted in the developing brain at E9.5.

A transgene that inserts the IRES-lacZ gene at the end of the catalytic domain of functional ADAMTS5 was able to inactivate this protein. The result is an ADAMTS5-knockout allele. The transgene acts as a functional protein and does not instigate the expression KLF2, KLF4, KLF4 nor KLF4.

Adamts5 is expressed in fetal brain tissues, and was also detected in the pericardium. It was also detected in parietal perineum, which linings the diaphragm. Adamts5 is a constitutive byproduct of mesothelial cell lines that line major body cavities. It plays an important role in neuromuscular growth.

Although human ADAMTS5's structure is similar to Aggrecan, thrombospondin and thrombospondins it cleaves at the glutamate Xaa recognition motif. It also contains a zinc binding group, which is essential for aggrecan recognition. It is important for the binding of ECM, as well as the regulation of fibroblast activity.

Sox4 comes from the SOX4 family. It plays an important role during skeletal development. It can also induce the overexpression ADAMTS5 from chondrogenic line cells. Sox4 binds with the promoter of ADAMTS5 by inhibiting b–gal expression. SOX4 can play a significant part in OA pathology.

ADAMTS5 plays a key role in the pathogenesis and formation of CCM, in addition to its role as a lesion-forming agent. Its proteolysis and cleavage of versican are crucial downstream mechanisms for CCM pathogenesis. Wild-type endothelial cell types also participate in lesion creation. These studies, while incomplete, offer a better understanding of ADAMTS5's role in the pathogenesis and development of cardiovascular disease.

Because they are complementary, siRNA and miRNA have specificity in inhibiting ADAMTS5 with their respective siRNAs. Nonspecific blocking of ADAMTS5 by siRNA or miRNA is not an option because it is involved multiple regulatory mechanisms. These methods are effective in targeting ADAMTS5 and constricting drug delivery by targeting its expression.

It is more active that ADAMTS429

The ADAMTS enzymes depend on carboxy-terminal domains to regulate activity and specify substrate-binding preferences. The ADAMTS13 ancillary domain contains 10 conserved cysteine residues and an O-fucosylated spacer region. This region can contain 103 to 160 different amino acids. Although they are not well-characterized, these domains may be involved with the regulation of enzyme catalytic activities.

The basic structure of ADAMTS consists of two domains. A carboxy-terminal and a catalytic domain. The ancillary domain controls substrate specificity. It also localizes substrates. These two domains are likely to have different biological functions. This review discusses the different subgroups of the ADAMTS family, with a particular focus on aggrecanases. It also offers insight into the evolutionary history and connections between ADAMTS and disease mechanisms.

19 genes are part of the ADAMTS gene family. One of these genes, ADAMTS111, is a member to the metzincin protease superfamily. These enzymes, which are related to ADAMs as well as matrix metalloproteinases (ADAMs), have a conserved residue of methionine near the zinc ion dependent metalloproteinase Domain. The family is present in all metazoan species but their presence has not yet been confirmed in single-cell organisms or plants.

ADAMTSs inhibit key survival and proliferative signaling pathways, including Akt/mTOR. They also inhibit breast carcinoma cell migration by increasing levels of syndecan-4 within the tumor microenvironment. The study was published in Cancer Res. 70 (2010). There are many other publications on the role ADAMTSs play in cancer. Many of these proteins are involved both in the development and metastatic spread of cancers.

The differences between ADAMTSs and MMPs have important implications for the design of selective ADAMTS inhibitors. Specifically, MMP inhibitors inhibit the activity of the TIMP-3 molecule. MMP activity is inhibited via the amino-terminal cysteine residues of ADAMTS4/5. While this is important when designing an inhibitor for ADAMTS, it should not impair the activity MMPs.

During vertebrate evolution, the ADAMTS family has expanded and grown. This expansion is due to the complexity of the ECM, which has increased through duplication, retention and modification of ancestral gene. ADAMTS genes are also important in the development of skin and autopods. Mice with null variants of the gene can induce apoptosis in ADAMTS5 cells once they are more active that ADAMTS429.

ADAMTS1 plays a critical role in cardiovascular health. It also mediates structural remodeling of the cumulus oocyte matrix. ADAMTS5 may be a candidate for future therapeutic strategies. In addition, the function of this protein has been studied in human arterial disease. It has also been implicated with the development of some cardiomyopathies including heart failure.