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A DISINTEGRIN-LIKE AND METALLOPROTEINASE WITH THROMBOSPONDIN TYPE 1 MOTIF, 5; ADAMTS5 OKDB#: 1939
 Symbols: A DISINTEGRIN-LIKE AND METALLOPROTEINASE WITH THRO Species: human
 Synonyms: AGGRECANASE 2| ADAMTS11, FORMERLY|  Locus: 21q21-q22 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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R-L INTERACTIONS   MGI

DNA Microarrays
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link to BioGPS
General Comment NCBI Summary: This gene encodes a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5), which is a member of the ADAMTS 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 enzyme encoded by this gene contains 2 C-terminal TS motifs and functions as aggrecanase to cleave aggrecan, a major proteoglycan of cartilage. This gene is composed of 8 exons.
General function Enzyme
Comment
Cellular localization Secreted
Comment
Ovarian function Follicle development, Ovulation, Follicle rupture, Luteinization
Comment
Expression regulated by
Comment
Ovarian localization Granulosa, Luteal cells
Comment Madan P et al 2003 reported the expression of Messenger RNA for ADAMTS Subtypes Changes in the Periovulatory Follicle After the Gonadotropin Surge and During Luteal Development and Regression in Cattle. Extensive remodeling of the extracellular matrix occurs in the ovary during the periovulatory period. Although matrix metalloproteinases and their endogenous inhibitors, tissue inhibitors of metalloproteinases, are believed to play integral roles in this highly regulated series of cellular events, their specific roles remain unclear. Recent cloning studies have identified a novel family of metalloproteinases, the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family. The regulated expression of distinct ADAMTS subtypes has been shown to be required for tissue morphogenesis during embryonic development and for maintaining the integrity of tissues in the adult. In these studies, multiple ADAMTS subtypes were found in the bovine ovary using a reverse transcription-polymerase chain reaction strategy. In particular, ADAMTS-1, -2, -3, -4, -5 (also known as ADAMTS-11), -7, -8 and -9 but not ADAMTS-6, -10, or -12 mRNA transcripts were detected in granulosa cells of non-atretic ovarian follicles and corpora lutea. The levels of mRNA for these ovarian ADAMTS were up-, or down-regulated or remained unchanged in the granulosa and/or theca cells of the dominant follicle following the preovulatory surge of gonadotropins depending on the subtype and/or the cell compartment and in the corpus luteum during the luteal phase of the estrous cycle. The complex expression patterns observed for the distinct ADAMTS subtypes in the granulosa and theca cells of the periovulatory follicle and in luteal tissues of the bovine ovary suggest that these novel proteases mediate, at least in part, the remodeling events underlying folliculogenesis and ovulation and the formation, maintenance and regression of the corpus luteum.
Follicle stages Preovulatory, Corpus luteum
Comment Richards JS, et al 2005 reported regulated Expression of ADAMTS Family Members in Follicles and Cumulus Oocyte Complexes and Evidence for Specific and Redundant Patterns During Ovulation. Protease cascades are essential for many biological events including the LH induced process of ovulation. ADAMTS1 (A Disintegrin and Metalloproteinase with Thrombospondin-like repeats-1) is expressed and hormonally regulated in the ovary by LH and the progesterone receptor (PR). To determine if other family members might be expressed and regulated in the rodent ovary, those closely related to ADAMTS1 (ADAMTS4 and ADAMTS5) were analyzed in the mouse ovary by RT-PCR as well as by Western blot, immunohisto- and immunocytochemical analyses using highly specific antibodies. Prior to ovulation, ADAMTS4 and ADAMTS5 were co-expressed in granulosa cells of most follicles whereas ADAMTS5 was also present in granulosa cells of atretic follicles. Following ovulation, ADAMTS1 and ADAMTS4 (but not ADAMTS5) were expressed in multiple cell types, including those within the highly vascular ovulation cone that marks the site of follicle rupture, endothelial cells of newly forming corpora lutea as well as cumulus cells within the ovulated cumulus cell oocyte complex (COC). Versican, a substrate for ADAMTS1 and ADAMTS4, co-localized with these proteases and hylauronan (HA) on the cumulus cell surface. To further characterize induction of these proteases and associated molecules, COCs and granulosa cells were isolated from preovulatory follicles and treated with FSH. In expanded COCs and differentiated granulosa cells, FSH induced expression of ADAMTS4 and versican message and protein whereas increased levels of ADAMTS1 protein were observed in the media of granulosa cells where it was stabilized by heparin in this in vitro system. These studies provide the first evidence that ADAMTS1, ADAMTS4 and ADAMTS5 are expressed in spacio-temporal patterns that suggest distinct as well as some overlapping functions, that relate to the broad expression pattern of versican in granulosa cells of small follicles, expanded COCs, and endothelial cells of the mouse ovary.
Phenotypes
Mutations 1 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Stanton H et al. Aggrecan is the major proteoglycan in cartilage, endowing this tissue with the unique capacity to bear load and resist compression. In arthritic cartilage, aggrecan is degraded by one or more 'aggrecanases' from the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteinases. ADAMTS1, 8 and 9 have weak aggrecan-degrading activity. However, they are not thought to be the primary aggrecanases because ADAMTS1 null mice are not protected from experimental arthritis, and cleavage by ADAMTS8 and 9 is highly inefficient. Although ADAMTS4 and 5 are expressed in joint tissues, and are known to be efficient aggrecanases in vitro, the exact contribution of these two enzymes to cartilage pathology is unknown. Here we show that ADAMTS5 is the major aggrecanase in mouse cartilage, both in vitro and in a mouse model of inflammatory arthritis. Our data suggest that ADAMTS5 may be a suitable target for the development of new drugs designed to inhibit cartilage destruction in arthritis, although further work will be required to determine whether ADAMTS5 is also the major aggrecanase in human arthritis.

Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
KEGG Pathways
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created: July 19, 2003, 5:50 p.m. by: hsueh   email:
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last update: Sept. 6, 2006, 12:10 p.m. by: hsueh    email:



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