4a3o | pdb_00004a3o
CRYSTAL STRUCTURE OF THE USP15 DUSP-UBL MONOMER
Structural highlights
Function[UBP15_HUMAN] Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedUSP4, 11 and 15 are three closely related paralogues of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. The DUSP domain and the UBL domain in these proteins are juxtaposed which may provide a functional unit conferring specificity. We determined the structures of the USP15 DUSP-UBL double domain unit in monomeric and dimeric states. We then conducted comparative analysis of the structural and physical properties of all three DUSP-UBL units. We identified structural features that dictate different dispositions between constituent domains, which in turn may influence respective binding properties. Structured summary of protein interactions: USP15 and USP15bind by molecular sieving (View Interaction: 1, 2) USP15 and USP15physically interact by molecular sieving (View interaction) USP4 and USP4bind by molecular sieving (View Interaction: 1, 2) USP15 and USP15bind by X ray scattering (View interaction) USP11 and USP11bind by molecular sieving (View interaction) USP4 and USP4bind by nuclear magnetic resonance (View interaction) USP15 and USP15bind by X-ray crystallography (View interaction). Structural variability of the ubiquitin specific protease DUSP-UBL double domains.,Elliott PR, Liu H, Pastok MW, Grossmann GJ, Rigden DJ, Clague MJ, Urbe S, Barsukov IL FEBS Lett. 2011 Nov 4;585(21):3385-90. Epub 2011 Oct 10. PMID:22001210[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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