SEARCH · PubMed Health

Results for “ADAMTS4 Protein”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2006

Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines.

ADAMTS-4 (aggrecanase-1) is a metalloprotease that plays a role in aggrecan degradation in the cartilage extracellular matrix. In order to understand the regulation of ADAMTS-4 gene expression we have cloned and characterized a functional 4.5kb human ADAMTS-4 promoter. Sequence analysis of the promoter revealed the presence of putative binding sites for nuclear factor of activated T cells (NFAT) and Runx family of transcription factors that are known to regulate chondrocyte maturation and differentiation. Using promoter-reporter assays and mRNA analysis we have analyzed the role of chondrocyte-expressed transcription factors NFATp and Runx2 and have shown that ADAMTS-4 is a potential downstream target of these two factors. Our results suggest that inhibition of the expression/function of NFATp and/or Runx2 may enable us to modulate aggrecan degradation in normal physiology and/or in degenerative joint diseases. The ADAMTS-4 promoter would serve as a valuable mechanistic tool to better understand the regulation of ADAMTS-4 expression by signaling pathways that modulate cartilage matrix breakdown.

ADAM Proteins↗

PubMed2005

Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors.

Aggrecanases are recently discovered enzymes that cleave aggrecan, a key component of cartilage. Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis. The synthesis and evaluation of biphenylsulfonamidocarboxylic acid inhibitors of aggrecanase-1 are reported. Compound 24 demonstrated 89% inhibition of proteoglycan degradation at 10 microg/mL and has an oral bioavailability in rat of 35%.

ADAM Proteins↗

PubMed2006

5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5.

A series of 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5 (aggrecanase-2) is described. These compounds show microM functional inhibition of ADAMTS-5, and represent a new class of agents with the potential of inhibiting degradation of aggrecan, a major component of cartilage which is lost in osteoporosis. Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1 microM and shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1).

ADAM Proteins↗

PubMed2006

ADAMTS-1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggest that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein were up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contributing to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.

ADAM Proteins↗

PubMed2004

Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes.

Interleukin (IL)-17 promotes cartilage breakdown by inducing matrix metalloproteinases (MMPs) and aggrecanases (a disintegrin and metalloproteinase with thrombospondin motif, ADAMTS) in arthritic joints. We investigated IL-17 signaling pathways inducing MMP-3, MMP-13 and ADAM-TS4 genes in bovine articular chondrocytes. IL-17 stimulated phosphorylation of extracellular signal-regulated kinase (ERK), protein 38 (p38) and c-Jun N-terminal kinase (JNK). ERK pathway inhibitors, PD98059 and U0126, down-regulated IL-17-induced MMP and ADAM-TS4 gene expression. Protein 38 and JNK pathway inhibitors, SB203580 and SP600125, also reduced induction of these genes. Antioxidants and activating protein-1 transcription factor inhibitors, nordihydroguaiaretic acid and N-acetyl-L-cysteine (NAC) suppressed MMP and ADAM-TS4 genes. Similarly, nuclear factor kappa B (NF-kappaB) pathways inhibitors curcumin and Bay-11-7085 also blocked their induction. Thus MMP-3, MMP-13 and ADAM-TS4 genes are coordinately up-regulated by IL-17 via MAP kinases, activating protein-1 (AP-1) and NF-kappaB mediators, which could be targeted for reducing IL-17-triggered cartilage damage.

ADAM Proteins↗

PubMed2004

GON-1 and fibulin have antagonistic roles in control of organ shape.

Most developing organs are surrounded by an extracellular matrix (ECM), which must be remodeled to accommodate growth and morphogenesis. In C. elegans, the GON-1 ADAMTS metalloprotease regulates both elongation and shape of the developing gonad . Here, we report that either human ADAMTS-4 or ADAMTS-9 can substitute for GON-1 in transgenic worms, suggesting functional conservation between human and nematode homologs. We further identify fibulin (FBL-1), a widely conserved ECM component , as critical for gonadal morphogenesis. FBL-1 is expressed in nongonadal tissues but is present at the surface of the elongating gonad. A fibulin deletion mutant has a wider than normal gonad as well as body size defects. We find that GON-1 and fibulin have antagonistic roles in controlling gonadal shape. Depletion of fbl-1, but not other ECM components, rescues gon-1 elongation defects, and removal of gon-1 rescues fbl-1 width defects. Therefore, the GON-1 protease normally promotes tissue elongation and expansion, whereas the fibulin ECM protein blocks these key morphogenetic processes. We suggest that control of organ shape by GON-1 and fibulin in C. elegans may provide a model for similar cellular processes, including vasculogenesis, in humans.

ADAM Proteins↗

PubMed2004

Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro.

OBJECTIVE: Aggrecan is degraded by Aggrecanases (ADAMTS-4 and -5) and MMPs, which cleave its core protein at different sites. Transforming growth factor (TGF)beta is known to stimulate matrix formation in cartilage, and ADAMTS-4 production in synoviocytes. The aim of this in-vitro study was to examine the effects of TGFbeta on aggrecanase production in human cartilage. DESIGN: Expression of ADAMTS-4 and -5 in chondrocyte cultures from normal or osteoarthritic cartilage was studied at mRNA level by RT-PCR. Aggrecanase activity was examined by western blot of aggrecanase-generated neoepitope NITEGE, and by measure of proteoglycan degradation in cartilage explants. RESULTS: TGFbeta strongly increased mRNA levels of ADAMTS-4, while ADAMTS-5 was expressed in a constitutive way in chondrocytes from normal and osteoathritic cartilage. TGFbeta also increased NITEGE levels and proteoglycan degradation. Addition of an aggrecanase inhibitor blocked the increase of NITEGE, and partially inhibited proteoglycan degradation. CONCLUSIONS: TGFbeta stimulates ADAMTS-4 expression and aggrecan degradation in cartilage. This catabolic action seems to be partially mediated by aggrecanases. It is, therefore, proposed that the role of TGFbeta in cartilage matrix turnover is not limited to anabolic and anti-catabolic actions, but also extends to selective degradation of matrix components such as aggrecan.

ADAM Proteins↗

PubMed2004

Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS-5 in primary bovine articular chondrocyte pellet culture system.

INTRODUCTION: Articular cartilage matrix synthesis and degradation are dynamic processes that must be balanced for proper maintenance of the tissue. In osteoarthritis (OA), this balance is skewed toward degradation and ultimate loss of matrix. The transcriptional and/or activity levels of hundreds of genes are dysregulated in chondrocytes from osteoarthritic cartilage, and a subset of these genes may represent pivotal factors that could be modulated if their specific role in the disease process could be identified. OBJECTIVE: To investigate the role of ADAMTS-4 and ADAMTS-5 in cartilage matrix degradation by developing a chondrocyte pellet culture assay in combination with adenoviral gene expression, and to demonstrate the utility of this assay by assessing the specific functional contribution of these genes to cartilage matrix metabolism. METHODS: A full-length cDNA for bovine ADAMTS-4 (bADAMTS-4) was isolated, and used to evaluate the expression, regulation, and activity of this gene in bovine cartilage. Adenoviruses expressing bADAMTS-4, human ADAMTS-5 (hADAMTS-5) or human bone morphogenetic protein 2 (BMP-2) were used to infect primary chondrocytes, and their effect on extracellular matrix metabolism was assessed by monitoring the accumulation and release of glycosaminoglycans (GAG) in three-dimensional chondrocyte pellet cultures. RESULTS: Analysis of bADAMTS-4 transcriptional regulation in chondrocytes revealed that interleukin-1alpha (IL-1alpha) was the most potent inducer of bADAMTS-4 mRNA and subsequent aggrecan degradation in cartilage explant cultures of those cytokines tested. bADAMTS-4 mRNA induction by IL-1alpha was greater in nasal cartilage than in articular cartilage. Chondrocytes infected with adenovirus expressing either bADAMTS-4 or hADAMTS-5 genes showed increased aggrecan degradation in newly synthesized matrix by pellet cultures while chondrocytes overexpressing BMP-2 showed increased aggrecan synthesis. CONCLUSION: Adenoviral delivery of genes to primary bovine chondrocytes, followed by culture in three-dimensional pellet format and evaluation of extracellular matrix protein metabolism, is a useful functional assay for assessing the role of genes on cartilage matrix synthesis and degradation.

ADAM Proteins↗

PubMed2006

Development and characterization of a highly specific and sensitive sandwich ELISA for detection of aggrecanase-generated aggrecan fragments.

OBJECTIVE: To develop an enzyme linked immunosorbent assay (ELISA) to quantify the levels of specific aggrecan fragments generated by aggrecanase-mediated cleavage at the 373Glu-374 Ala bond within the aggrecan interglobular domain. METHODS: The ELISA employs a commercially available monoclonal antibody to capture aggrecan fragments containing keratan sulfate (KS). Aggrecan fragments generated by cleavage at the Glu-Ala bond were then detected using a monoclonal neoepitope antibody (mAb OA-1) that specifically recognizes the N-terminal sequence 'ARGSVIL'. RESULTS: The mAb OA-1 antibody was highly specific for the immunizing neoepitope peptide since neither peptides spanning the cleavage site nor mutated peptides were detected. Aggrecan fragments generated by ADAMTS-4 digested human aggrecan monomers and from IL-1-stimulated human cartilage explants were quantified by the ELISA, and we observed increased sensitivity of the ELISA compared to mAb OA-1 Western analysis. We also observed that the basal, as well as IL-1-stimulated production of ARGS aggrecan fragments from human articular cartilage explants was blocked by a selective aggrecanase inhibitor, consistent with generation of the ARGS neoepitope in human articular cartilage being mediated by aggrecanase. Using purified human aggrecan digested by ADAMTS-4 as standard to quantify ARGS aggrecan fragments in human synovial fluids, we determined that the calculated amount of ARGSVIL-aggrecan fragments by ELISA measurement is in agreement with the published levels of these fragments, supporting its potential utility as a biomarker assay for osteoarthritis. CONCLUSION: We have developed an assay that detects and quantifies specific aggrecan fragments generated by aggrecanase-mediated cleavage. Because aggrecanase mediates degradation of human articular aggrecan in joint disease, the KS/mAb OA-1 ELISA may serve as a biomarker assay for evaluation of preclinical and clinical samples.

ADAM Proteins↗

PubMed2006

Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium.

OBJECTIVE: To investigate the immunolocalisation of beta-dystroglycan (beta-DG) and specific matrix metalloproteinases (MMPs)-3, -9, -13 and a disintegrin like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) within the joint tissues of patients with osteoarthritis (OA) and unaffected controls. DESIGN: Cartilage, synovium and synovial fluid were obtained from the hip joints of five osteoarthritic (patients undergoing total hip replacement) and five control hip joints (patients undergoing hemiarthroplasty for femoral neck fracture). The samples were analysed for beta-DG protein using Western blot technique and by immunohistochemistry for tissue distribution of beta-DG, MMP-3, -9, -13, and ADAMTS-4. RESULTS: beta-DG was detected in the smooth muscle of both normal and osteoarthritic synovial blood vessels. Importantly, beta-DG was detected in endothelium of blood vessels of OA synovium, but not in the control endothelium. In the endothelium of osteoarthritic synovial blood vessels, beta-DG co-localised with MMP-3 and -9. MMP-13 and ADAMTS-4 showed no endothelial staining, and only weak staining of the vascular smooth muscle was found. In contrast, we did not detect beta-DG protein in cartilage or synovial fluid. CONCLUSIONS: beta-DG has been shown to have a role in angiogenesis, and our results demonstrate for the first time that there are clear differences in beta-DG staining between OA and control synovial blood vessels. The specific immunolocalisation of beta-DG within endothelium of inflamed OA blood vessels and its co-localisation with MMP-3 and -9, reported to have pro-angiogenic roles and believed to be involved in beta-DG cleavage, may also suggest that beta-DG plays a role in angiogenesis accompanying OA.

ADAM Proteins↗

PubMed2006

The cleavage of biglycan by aggrecanases.

OBJECTIVE: Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4] and aggrecanase-2 (ADAMTS-5) have been named for their ability to degrade the proteoglycan aggrecan. While this may be the preferred substrate for these enzymes, they are also able to degrade other proteins. The aim of this work was to determine whether the aggrecanases could degrade biglycan and decorin. METHODS: Biglycan, decorin and aggrecan were purified from human and bovine cartilage and subjected to degradation by recombinant aggrecanase-1 or aggrecanase-2. In vitro degradation was assessed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) and immunoblotting, and the cleavage site in biglycan was determined by N-terminal amino acid sequencing. SDS/PAGE and immunoblotting were also used to assess in situ degradation in both normal and arthritic human articular cartilage. RESULTS: Both aggrecanase-1 and aggrecanase-2 are able to cleave bovine and human biglycan at a site within their central leucine-rich repeat regions. Cleavage occurs at an asparagine-cysteine bond within the fifth leucine-rich repeat. In contrast, the closely related proteoglycan decorin is not a substrate for the aggrecanases. Analysis of human articular cartilage from osteoarthritic (OA) and rheumatoid arthritic (RA) joints showed that a biglycan degradation product of equivalent size is present in the extracellular matrix. No equivalent degradation product was, however, detectable in normal adult human articular cartilage. CONCLUSION: Biglycan, which is structurally unrelated to aggrecan, can act as a substrate for aggrecanase-1 and aggrecanase-2, and these proteinases may account for at least part of the biglycan degradation that is present in arthritic cartilage.

ADAM Proteins↗

PubMed2006

A microplate assay for the screening of ADAMTS-4 inhibitors.

Aggrecanase plays a major role in cartilage proteoglycan degradation in rheumatic diseases such as osteoarthritis and rheumatoid arthritis. The search of new inhibitors of aggrecanase activity necessitates a robust assays in order to be able to screen large numbers of compounds. We present in this paper an assay based on the cleavage of His-tagged aggrecan interglobular domain by N- and C- terminus truncated, active aggrecanase-1/ADAMTS-4, with formation of the aggrecanase-specific ARGSV neoepitope. This is detected by anti-ARGSV antibody, in turn recognized by a fluorescent anti-IgG. Furthermore, the formation of the reaction products was confirmed by high-pressure capillary electrophoresis. This assay allows the rapid screening of aggrecanase inhibitors in a 96-well plate format, allowing an immediate transposition to high-throughput scale up.

ADAM Proteins↗

PubMed2006

Differential regulation of matrix degrading enzymes in a TNFalpha-induced model of nucleus pulposus tissue degeneration.

Intervertebral disc degeneration occurs commonly and is linked to persistent back pain and the development of disc herniation. The mechanisms responsible for tissue catabolism have not yet been fully elucidated. Previously we characterized an in vitro model of TNFalpha-induced nucleus pulposus degeneration, which demonstrates decreased expression of matrix macromolecules, increased expression of matrix degrading enzymes, and the activation of aggrecanase-mediated proteoglycan degradation [Seguin, C.A., Pilliar, R.M., Roughley, P.J., and Kandel, R.A. 2005. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine 30: 1940-1948]. This study explores the intracellular pathways activated during TNFalpha-induced matrix degradation. We demonstrate that in nucleus pulposus cells, the p38 and JNK pathways regulate induction of MMP-1 and -3; p38, JNK, and NF-kappaB regulate the induction of MMP-13; and ERK regulates the up-regulation of MT1-MMP mRNA in response to TNFalpha. Induction of ADAMTS-4 and -5 mRNA occurred downstream of NF-kappaB activation. Depletion of tissue proteoglycans was mediated by ERK and NF-kappaB-dependent "aggrecanase" activity, suggesting MT1-MMP and ADAMTS-4 and -5 as effectors of TNFalpha-induced tissue catabolism.

ADAM Proteins↗

PubMed2006

Effects of covalently attached chondroitin sulfate on aggrecan cleavage by ADAMTS-4 and MMP-13.

Aggrecan is degraded by several aggrecanase-1 (ADAMTS-4) isoforms differing in the number of sulfated glycosaminoglycan (sGAG)-binding motifs. ADAMTS-4 and MMPs cleave aggrecan more efficiently within the chondroitin sulfate (CS)-rich region than the interglobular domain (IGD). We investigated the influence of CS on aggrecan core protein cleavage by ADAMTS-4 (p68) and (p40) as well as MMP-13, which has no recognizable GAG-binding sites. Chondroitinase ABC-treated cartilage aggrecan was cleaved with ADAMTS-4 (p68) less efficiently than CS-substituted aggrecan within the CS-2 domain. Keratanase-treated aggrecan exhibited reduced IGD cleavage, but when both CS and KS were removed, the IGD cleavage was restored. This result suggests that KS in the IGD may compete with CS for ADAMTS-4 (p68) binding. In the absence of KS, however, p68 binding was shifted to the CS-2 domain. CS-deficient full-length recombinant aggrecan (rbAgg) was produced by chondroitinase ABC treatment, or by expression in the xylosyltransferase-deficient CHO-pgsA745 cell line. When digested with the ADAMTS-4 (p68), each of these preparations exhibited reduced CS-2 domain cleavage compared to CS-substituted CHO-K1 cell-derived aggrecan. Additionally, CS-deficient rbAgg showed increased IGD scission prior to cleavage within the CS-2 domain. ADAMTS-4 (p40) readily cleaved both rbAggs within the IGD, but cleaved poorly within the CS-2 domain, indicating little CS dependence. MMP-13, in contrast, cleaved the CS region and the IGD of both CS-substituted and CS-deficient rbAgg equally well. These data indicate that covalently bound CS enhances ADAMTS-4-mediated cleavage within the CS-rich region. MMP-13 also cleaves preferentially within the CS-region, but by an apparently CS-independent mechanism.

ADAM Proteins↗

PubMed2004

Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection.

Disruption of the perineuronal matrix has been reported in human immunodeficiency virus (HIV) encephalitis. To better understand the extent of matrix disruption during lentiviral encephalitis, we characterized the extracellular matrix (ECM) damage in brains of 12 macaques infected with simian immunodeficiency virus (SIV). Matrix integrity was assessed by Wisteria floribunda lectin histochemistry. Confocal microscopy was used to quantify matrix loss, macrophage infiltration, and synaptic damage. Disruption of brain ECM was present shortly after retroviral infection, preceding parenchymal macrophage infiltration. In agreement with previous observations, reduced staining of presynaptic and postsynaptic proteins in SIV encephalitis occurred concurrently with matrix abnormalities. Lentiviral infection induced microglial and macrophage expression of two disintegrins and metalloproteinases with thrombospondin motifs (ADAMTS-1 and ADAMTS-4), with high substrate specificity for matrix proteoglycans. Matrix damage is pervasive during SIV neuroinfection, which suggests interventions to conserve brain matrix proteoglycans might avert or delay retroviral-induced neurodegeneration.

ADAM Proteins↗

PubMed2004

Anabolic and catabolic mRNA levels of the intervertebral disc vary with the magnitude and frequency of in vivo dynamic compression.

The goal of this study was to characterize the anabolic and catabolic mRNA response of the disc to dynamic loading to determine if variations in the magnitude and/or frequency of loading could elicit different cellular responses. Sixty-eight Wistar rats were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Seventy-two hours after surgery, animals were anesthetized and loaded at either 1 or 0.2 MPa at a frequency of 1, 0.2 or 0.01 Hz for 2 h (6 groups). The surgical control (Sham) animals underwent anesthesia with no loading. Loaded (c8-9) and internal-control discs (c6-7 and c10-11) were dissected and annulus and nucleus tissue were separately analyzed by real-time RT-PCR for levels of anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) mRNA. In the nucleus, a frequency-dependent response was seen at 1 MPa with anabolic genes stimulated at 0.01 Hz and catabolic genes at 1 Hz. In the annulus all frequencies resulted in significant up-regulation of catabolic mRNA at 1 MPa loading. In general loading at 0.2 MPa or 0.2 Hz had little effect on gene expression. The results suggest that gene expression of the annulus appears to be more dependent on the magnitude of applied stress, while the nucleus is both magnitude- and frequency-dependent.

ADAM Proteins↗

PubMed2005

The effects of short-term load duration on anabolic and catabolic gene expression in the rat tail intervertebral disc.

The goal of this study was to determine the time-dependent response of the intervertebral disc cells to in vivo dynamic compression. Forty-seven skeletally mature Wistar rats (>12 months old) were instrumented with an Ilizarov-type device spanning caudal disc 8-9. Using a load magnitude (1 MPa) and frequency (1.0 Hz) that were previously shown to significantly alter mRNA levels in the disc, the effects of 0.5 and 4 h of loading were investigated and compared to a sham group and our previous 2 h results. Annulus and nucleus tissue of loaded (c8-9) and internal control discs (c6-7 and c10-11) were separately analyzed by real-time RT-PCR for levels of mRNA coding for various anabolic (collagen-1A1, collagen-2A1, aggrecan) and catabolic (MMP-3, MMP-13, ADAMTs-4) proteins. In the annulus, mRNA levels increased for Collagen types I & II, and MMP 3 & 13 with increasing load duration. In contrast, the nucleus had the largest increases in aggrecan, ADAMTs-4, MMP-3 and MMP-13 after 2 h of loading, with aggrecan and MMP-13 mRNA levels returning to control values after 4 h of loading. Taken in context with our previous studies, we conclude that intervertebral disc cells from the nucleus and annulus have distinct responses to dynamic mechanical compression in vivo with sensitivity to compression magnitude, frequency and duration.

ADAM Proteins↗

PubMed2001

Characterization of ADAMTS14, a novel member of the ADAMTS metalloproteinase family.

ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 modules) proteins constitute a family of zinc metalloproteinases which target and process extracellular matrix proteins. We cloned and characterized a novel human ADAMTS gene, ADAMTS14, which is located on human chromosome 10q2. ADAMTS14 exhibits the characteristic multidomain structure of ADAMTS proteins including four thrombospondin modules and shows highest similarity to ADAMTS3 and ADAMTS2. By RT-PCR analysis we demonstrated that ADAMTS14 is expressed in human retina and also at low levels in adult brain, lung and placenta.

ADAM Proteins↗