{"product_id":"recombinant-e3-ligase-ubr5hectg2216-v2799gsgsgsδe2307-d2499","title":"Recombinant \u003cb\u003eUBR5\u003c\/b\u003e (G2216-V2799)GSGSGS(ΔE2307-D2499), HECT Domain, Ubiquitin Protein E3 Ligase Component N-Recognin 5","description":"\u003cp\u003e\u003cmeta charset=\"UTF-8\"\u003e \u003cmeta name=\"viewport\" content=\"width=device-width, initial-scale=1.0\"\u003e\u003c\/p\u003e\n\u003cstyle\u003e\n    \/* 1. VARIABLEN \u0026 RESET *\/\n    :root {\n        --primary-color: #0dbaad;\n        --text-dark: #373636;\n        --border-light: #e0e0e0;\n    }\n\n    * { margin: 0; padding: 0; box-sizing: border-box; }\n\n    .container {\n        max-width: 1200px;\n        margin: 0 auto;\n        background-color: white;\n        padding: 20px;\n        font-family: \"Source Sans Pro\", sans-serif;\n        color: var(--text-dark);\n        line-height: 1.6;\n    }\n\n    \/* 2. 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AKKORDEON \u0026 INNEN-ÜBERSCHRIFTEN *\/\n    .accordion-container {\n        border-top: 1px solid var(--border-light);\n        margin: 20px 0;\n    }\n    .accordion-item {\n        border-bottom: 1px solid var(--border-light);\n    }\n    .accordion-header {\n        width: 100%;\n        padding: 20px 0;\n        background: none;\n        border: none;\n        display: flex;\n        justify-content: space-between;\n        align-items: center;\n        font-family: inherit;\n        font-size: 25px;\n        color: var(--primary-color) !important; \/* Türkis für Haupt-Header *\/\n        text-transform: uppercase;\n        cursor: pointer;\n        text-align: left;\n    }\n\n    \/* Styling für h4 Überschriften im Scientific Context *\/\n    .content-inner h4 {\n        color: var(--primary-color) !important;\n        text-transform: uppercase;\n        margin: 20px 0 10px 0;\n        font-size: 20px;\n    }\n\n    .icon { position: relative; width: 20px; height: 20px; flex-shrink: 0; margin-left: 10px; }\n    .icon::before, .icon::after {\n        content: '';\n        position: absolute;\n        background-color: currentColor;\n        transition: transform 0.3s ease;\n    }\n    .icon::before { width: 100%; height: 2px; top: 50%; left: 0; transform: translateY(-50%); }\n    .icon::after { width: 2px; height: 100%; left: 50%; top: 0; transform: translateX(-50%); }\n    .accordion-item.active .icon::after { transform: translateX(-50%) rotate(90deg); opacity: 0; }\n\n    .accordion-content {\n        max-height: 0;\n        overflow: hidden;\n        transition: max-height 0.5s cubic-bezier(0, 1, 0, 1);\n    }\n    .accordion-item.active .accordion-content {\n        max-height: 4000px;\n        transition: max-height 1s ease-in-out;\n    }\n    .content-inner { padding: 15px 0 35px 0; font-size: 19px; }\n\n    .sequence-box {\n        word-break: break-all;\n        font-family: monospace;\n        background: #f4f4f4;\n        padding: 15px;\n        font-size: 15px;\n        border-left: 4px solid var(--primary-color);\n        margin-top: 10px;\n    }\n\n    \/* 5. MOBILE ANPASSUNGEN *\/\n    @media (max-width: 600px) {\n        .product-top-section {\n            flex-direction: column;\n            align-items: center;\n        }\n        .image-column {\n            order: -1;\n            margin-bottom: 20px;\n            width: 100%;\n        }\n        .side-image {\n            margin-top: 0;\n            margin-left: auto;\n            margin-right: auto;\n        }\n        .custom-list { font-size: 17px; }\n        .accordion-header { font-size: 20px; }\n    }\n\/* 6. INTRO TEXT SEKTION *\/\n    .intro-section {\n        margin: 20px 0;\n        font-size: 19px; \/* Desktop Größe *\/\n        line-height: 1.8;\n    }\n\n    \/* Mobile Anpassung für den Intro-Text *\/\n    @media (max-width: 600px) {\n        .intro-section {\n            font-size: 17px; \n            text-align: left;\n            padding: 0 5px;\n        }\n    }\n  \n\u003c\/style\u003e\n\u003cdiv class=\"container\"\u003e\n\u003cdiv class=\"product-top-section\"\u003e\n\u003cdiv class=\"info-column\"\u003e\n\u003cul class=\"custom-list\"\u003e\n\u003cli\u003eCrystallizable\u003c\/li\u003e\n\u003cli\u003ePurity \u0026gt; 95%\u003c\/li\u003e\n\u003cli\u003eMonodisperse\u003c\/li\u003e\n\u003cli\u003eMelting temperature of 48°C\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"image-column\"\u003e\u003cimg class=\"side-image\" alt=\"Quality Plus Siegel\" src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/Stempel-QUALITY-PLUS-new.png?v=1771953936\"\u003e\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr\u003e\n\u003cdiv class=\"intro-section\"\u003e\n\u003cp\u003eThe nuclear UBR5 HECT E3 Ligase is a key regulator of cellular functions such as mitotic progression or DNA replication, as it transfers ubiquitin molecules to a wide range of substrates, thereby marking them for proteasomal degradation.\nOur recombinant UBR5(HECT) protein is of high, crystallography-grade quality and is well suited for researchers pursuing the development of therapeutics for targeted protein degradation.\n\u003c\/p\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003econstruct design\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003eThe construct includes the catalytic HECT-domain of UBR5 spanning residues G2216-V2799. Part of the MLLE domain was deleted (ΔE2307-D2499) and replaced with a flexible linker (GSGSGS) as part of a crystallization strategy. The catalytic cysteine in the C-terminal lobe (C-lobe) as well as the E2-binding site in the N-terminal lobe ( N-lobe) are accessible for soaking of small and middle-sized compounds.\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eProtein Properties \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eProtein Construct:\u003c\/b\u003e UBR5(HECT)(G2216-V2799)GSGSGS(ΔE2307-D2499) \n\u003cbr\u003e\u003cb\u003eSource:\u003c\/b\u003e Human\u003cbr\u003e\u003cb\u003eExpression Host:\u003c\/b\u003e \u003ci\u003eEscherichia coli\u003c\/i\u003e\u003cbr\u003e\u003cb\u003eMolecular weight [kDa]:\u003c\/b\u003e 45.1\u003cbr\u003e\u003cb\u003epI:\u003c\/b\u003e 8.39\u003cbr\u003e\u003cb\u003eExtinction Coefficient [M\u003csup\u003e-1\u003c\/sup\u003ecm\u003csup\u003e-1\u003c\/sup\u003e]:\u003c\/b\u003e 36900\u003cbr\u003e\u003cb\u003eConcentration:\u003c\/b\u003e 34.27 mg\/mL\u003cbr\u003e\u003cb\u003eStorage Buffer:\u003c\/b\u003e 20 mM HEPES pH 7.4, 200 mM NaCl, 0.5 mM TCEP, 5% glycerol \u003cbr\u003e\u003cb\u003eTag:\u003c\/b\u003e none\u003c\/p\u003e\n\u003cp style=\"margin-top: 15px;\"\u003e\u003cb\u003eAmino acid sequence:\u003c\/b\u003e\u003c\/p\u003e\n\u003cdiv class=\"sequence-box\"\u003eGGFEVKESKFRREMEKLRNQQSRDLSLEVDRDRDLLIQQTMRQLNNHFGRRCATTPMAVHRVKVTFKDEPGEGSGVARSFYTAIAQAFLSNGSGSGSDNAPLFYQPGKRGFYTPRPGKNTEARLNCFRNIGRILGLCLLQNELCPITLNRHVIKVLLGRKVNWHDFAFFDPVMYESLRQLILASQSSDADAVFSAMDLAFAIDLCKEEGGGQVELIPNGVNIPVTPQNVYEYVRKYAEHRMLVVAEQPLHAMRKGLLDVLPKNSLEDLTAEDFRLLVNGCGEVNVQMLISFTSFNDESGENAEKLLQFKRWFWSIVEKMSMTERQDLVYFWTSSPSLPASEEGFQPMPSITIRPPDDQHLPTANTCISRLYVPLYSSKQILKQKLLLAIKTKNFGFV\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eQuality Plus\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eQC Data:\u003c\/b\u003e \u003ca href=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/UBR5_datasheet_NewVersion.pdf?v=1776158056\" target=\"_blank\"\u003eDatasheet\u003c\/a\u003e\u003cbr\u003e\u003cb\u003ePurity SDS:\u003c\/b\u003e \u0026gt;95 % \u003cbr\u003e\u003cb\u003eHydrodynamic Radius (nm):\u003c\/b\u003e 3.7\u003cbr\u003e\u003cb\u003ePolydispersity Index (PDI): \u003c\/b\u003e 0.1\u003cbr\u003e\u003cb\u003eT\u003csub\u003eon\u003c\/sub\u003e (°C):\u003c\/b\u003e 43.9\u003cbr\u003e\u003cb\u003eT\u003csub\u003em\u003c\/sub\u003e (°C):\u003c\/b\u003e 48.1\u003cbr\u003e\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eScientific context \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003ch4\u003eStructure and function\u003c\/h4\u003e\n\u003cp\u003eThe nuclear E3 Ligase UBR5 belongs to the family of HECT Ligases, which is next to RING E3 Ligases one of the two major E3 Ligase classes. HECT Ligases typically operate as single-chain enzymes, incorporating both substrate-binding and catalytic components within the same polypeptide structure. The HECT domain itself consists of a large N-lobe which recruits E2-ubiquitin complexes and a smaller C-lobe which contains the catalytic cysteine involved in ubiquitin transfer. \nThe basis for the recognition of a wide range of substrates is given through a high degree of structural heterogeneity that enables independence from adaptor proteins. The catalytic C-terminal HECT-domain, though, is highly conserved throughout the HECT-type E3 ligases: It catalyzes the ubiquitin transfer from the ubiquitin-loaded E2 to the substrate and thus determines UBR5 activity. Interestingly, recent research indicates that UBR5 has a preference for already ubiquitinated substrates, and might act as an efficient ubiquitin chain elongator (Hodakova, 2023). UBR5 typically occurs in a dimeric state that can further oligomerize into trimers or tetramers.\n\u003c\/p\u003e\n\n\u003cbr\u003e\n\u003ch4\u003eUBR5 as an important drug target\u003c\/h4\u003e\n\u003cp\u003eUBR5 has been associated with tumor-suppressing effects as well as enhancement of tumor growth, which can be explained by the large substrate diversity of UBR5. Especially its localisation in the nucleus, makes UBR5 an interesting target in the cancer therapeutics field. One example is the suppression of UBR5 in pancreatic cancer, which has been shown to raise the chemotherapeutic sensitivity of pancreatic cancer cells to Gemcitabine - a pancreatic tumor suppressor (Du et al., 2024). \nApart from that, the UBR5 drug development approach focuses on harnessing its activity to degrade oncogenic proteins like transcription factors or nuclear receptors via targeted protein degradation. Here, strategies involve enhancing the degradation of native UBR5-targets by molecular glues that improve substrate recruitment or ligands that expose the degron sequence of e.g. oncogenic transcription factors (Taherbhoy et al., 2023). \n\u003c\/p\u003e\n\u003cbr\u003e\n\u003cdiv style=\"font-size: 15px; margin-top: 25px; border-top: 1px dotted #ccc; padding-top: 15px;\"\u003e\n\u003cb\u003eReferences:\u003c\/b\u003e \u003cbr\u003eHodáková Z, Grishkovskaya I, Brunner HL, Bolhuis DL, Belačić K, Schleiffer A, Kotisch H, Brown NG, Haselbach D.\u003cb\u003e(2023)\u003c\/b\u003e Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5. \u003cb\u003eEMBO Journal.\u003c\/b\u003e doi: \u003ca href=\"https:\/\/link.springer.com\/article\/10.15252\/embj.2022113348\" target=\"_blank\"\u003e10.15252\/embj.2022113348.\u003c\/a\u003e\n  \n\u003cbr\u003e\u003cbr\u003eDu, Y., Yang, Z., Shi, H. et al. \u003cb\u003e(2024)\u003c\/b\u003e.E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA. \u003cb\u003eNature.\u003c\/b\u003e doi: \u003ca href=\"https:\/\/www.nature.com\/articles\/s41419-024-06729-z\" target=\"_blank\"\u003e10.1038\/s41419-024-06729-z\u003c\/a\u003e\n\n\u003cbr\u003e\u003cbr\u003eTaherbhoy, Asad M., Daniels, Danette L. \u003cb\u003e(2023)\u003c\/b\u003e. Harnessing UBR5 for targeted protein degradation of key transcriptional regulators. \u003cb\u003eCell Press.\u003c\/b\u003e doi: \u003ca href=\"https:\/\/doi.org\/10.1016\/j.tips.2023.09.001\" target=\"_blank\"\u003e10.1016\/j.tips.2023.09.001\u003c\/a\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e","brand":"CrystalsFirst Shop","offers":[{"title":"1 mg","offer_id":57272836981119,"sku":null,"price":1500.0,"currency_code":"EUR","in_stock":true},{"title":"5 mg","offer_id":57272837013887,"sku":null,"price":6750.0,"currency_code":"EUR","in_stock":true},{"title":"10 mg","offer_id":57272837046655,"sku":null,"price":12000.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/UBR5-purple.jpg?v=1778612727","url":"https:\/\/shop.crystalsfirst.com\/products\/recombinant-e3-ligase-ubr5hectg2216-v2799gsgsgs%ce%b4e2307-d2499","provider":"CrystalsFirst GmbH","version":"1.0","type":"link"}