This entry includes proteins with reprolysin-like metallopeptidase domains and includes ADAM10 (also known as myelin-associated metalloendopeptidase, MEROPS identifier M12.210), ADAM17 (also known as tumour necrosis factor alpha-convertase, MEROPS identifier M12.217), kuzbanian (MEROPS identifiers M12.211 and M12.322) and ADM-4 (MEROPS identifier M12.329) [].
Disintegrin and metalloproteinase domain-containing protein 10 (also known as ADAM10 or Kuzbanian; MEROPS identifier M12.210) is an endopeptidase () []. In humans and mice, it cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. It is responsible for the proteolytic release of several other cell-surface proteins. It controls the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis []. The Drosophila orthologue is classified separately in the MEROPS database as M12.211.
Ras-related protein Rab14 is a small GTPase that mediates endocytic recycling and functions in phagosome maturation [, ]. Rab14 and its exchange factor FAM116 regulates the specific endocytic transport of ADAM10 and thereby N-cadherin shedding and cell motility [, ]. Rab14 regulates claudin-2 trafficking, which is required for epithelial morphogenesis []. It regulates apical targeting in polarised epithelial cells []. Rab14 also regulates the interaction of phagosomes with early endocytic compartments and the maturation of macrophage phagosomes containing the fungal pathogen Candida albicans []. Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus aureus [].
The family of type 2 integral membrane protein (ITM2) consists of three members, ITM2A, ITM2B and ITM2C []. Members of this family contain a BRICHOS domain, which possesses chaperone activity [,].ITM2A is a target gene of GATA-3, a T cell-specific transcription factor [].ITM2B is proteolytically cleaved at three locations; cleavage by furin in the C-terminal region generates a 23-residue peptide (ABri23), processing by ADAM10 results in release of the BRICHOS domain from the membrane-bound N-terminal part and intramembrane cleavage by SPPL2a/2b liberates the intracellular domain []. ITM2B (BRI2) is a target of BCL6 transcriptional repression and a short form of the ITM2B protein, similarly to other targets of BCL6, induces apoptosis in hematopoietic cell lines []. ITM2B interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production [, ]. ITM2C (BRI3) also inhibits amyloid precursor protein processing, but through a different mechanism to ITM2B [].
This entry includes the alpha subunit of meprin (MEROPS identifier M12.002).Meprins are metazoan zinc metallopeptidases belonging to MEROPS peptidase family M12 (clan MA(M)), subfamily M12A (astacin family). They are complex and structurally unique homo- or heterotetrameric glycoproteins composed of evolutionarily related alpha and/or beta subunits that contain disulphide-bridged dimers. The two subunits are differentially expressed and processed to yield latent and active proteases as well as membrane-associated and secreted forms. They are excellent models of homo- and hetero-oligomeric enzymes that are regulated at the transcriptional and post translational levels []. Each chain contains an astacin domain, MAM, MATH, and AM (after MATH) domains [], and an EGF-like domain.The astacin domain is a Zn-metalloprotease domain characterised by a unique 18-amino acid signature sequence, HEXXHXXGFXHEXXRXDR [], which begins with the zinc binding motif HEXXH. The MAM domain is necessary for correct folding and transport through the secretory pathway. The MATH domain is required for folding of an activatable zymogen, and the AM domain is important for activity against proteins and efficient secretion of the protein. Meprin is able to cleave a variety of substrates and has a role in matrix remodeling, inflammation, and cell-cell and cell-matrix processes []. Known substrates include FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10 and tenascin-C [].
Meprins are metazoan zinc metallopeptidases belonging to MEROPS peptidase family M12 (clan MA(M)), subfamily M12A (astacin family). They are complex and structurally unique homo- or heterotetrameric glycoproteins composed of evolutionarily related alpha and/or beta subunits that contain disulphide-bridged dimers. The two subunits are differentially expressed and processed to yield latent and active proteases as well as membrane-associated and secreted forms. They are excellent models of homo- and hetero-oligomeric enzymes that are regulated at the transcriptional and post translational levels []. Each chain contains an astacin domain, MAM, MATH, and AM (after MATH) domains [], and an EGF-like domain.The astacin domain is a Zn-metalloprotease domain characterised by a unique 18-amino acid signature sequence, HEXXHXXGFXHEXXRXDR [], which begins with the zinc binding motif HEXXH. The MAM domain is necessary for correct folding and transport through the secretory pathway. The MATH domain is required for folding of an activatable zymogen, and the AM domain is important for activity against proteins and efficient secretion of the protein. Meprin is able to cleave a variety of substrates and has a role in matrix remodeling, inflammation, and cell-cell and cell-matrix processes []. Known substrates include FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10 and tenascin-C [].
This entry represents the meprin beta subunit (MEROPS identifier M12.004).Meprins are metazoan zinc metallopeptidases belonging to MEROPS peptidase family M12 (clan MA(M)), subfamily M12A (astacin family). They are complex and structurally unique homo- or heterotetrameric glycoproteins composed of evolutionarily related alpha and/or beta subunits that contain disulphide-bridged dimers. The two subunits are differentially expressed and processed to yield latent and active proteases as well as membrane-associated and secreted forms. They are excellent models of homo- and hetero-oligomeric enzymes that are regulated atthe transcriptional and post translational levels []. Each chain contains an astacin domain, MAM, MATH, and AM (after MATH) domains [], and an EGF-like domain.The astacin domain is a Zn-metalloprotease domain characterised by a unique 18-amino acid signature sequence, HEXXHXXGFXHEXXRXDR [], which begins with the zinc binding motif HEXXH. The MAM domain is necessary for correct folding and transport through the secretory pathway. The MATH domain is required for folding of an activatable zymogen, and the AM domain is important for activity against proteins and efficient secretion of the protein. Meprin is able to cleave a variety of substrates and has a role in matrix remodeling, inflammation, and cell-cell and cell-matrix processes []. Known substrates include FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10 and tenascin-C [].
