2 μg DDB1/CRBN run on 4-12% SDS-PAGE gel under reducing conditions, then visualized with Colloidal Coomassie Blue Stain.
Formulation: 40 mM HEPES, 100 mM NaCl, 10% Glycerol, 1 mM EDTA, 1 mM TCEP, pH 7.6
Shipping: The product is shipped with dry ice or equivalent. Upon receipt, store it immediately at the temperature recommended below.
Storage and Stability: Use a manual defrost freezer and avoid repeated freeze-thaw cycles. Aliquot and store ≤ -70°C (stable for 24 months from date of receipt).
Protein Sequence: MGHHHHHHHHGSENLYFQSMAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL;MWSHPQFEKGGGSGGGSGGSAWSHPQFEKGSLEVLFQGPMSYNYVVTAQKPTAVNGCVTGHFTSAEDLNLLIAKNTRLEIYVVTAEGLRPVKEVGMYGKIAVMELFRPKGESKDLLFILTAKYNACILEYKQSGESIDIITRAHGNVQDRIGRPSETGIIGIIDPECRMIGLRLYDGLFKVIPLDRDNKELKAFNIRLEELHVIDVKFLYGCQAPTICFVYQDPQGRHVKTYEVSLREKEFNKGPWKQENVEAEASMVIAVPEPFGGAIIIGQESITYHNGDKYLAIAPPIIKQSTIVCHNRVDPNGSRYLLGDMEGRLFMLLLEKEEQMDGTVTLKDLRVELLGETSIAECLTYLDNGVVFVGSRLGDSQLVKLNVDSNEQGSYVVAMETFTNLGPIVDMCVVDLERQGQGQLVTCSGAFKEGSLRIIRNGIGIHEHASIDLPGIKGLWPLRSDPNRETDDTLVLSFVGQTRVLMLNGEEVEETELMGFVDDQQTFFCGNVAHQQLIQITSASVRLVSQEPKALVSEWKEPQAKNISVASCNSSQVVVAVGRALYYLQIHPQELRQISHTEMEHEVACLDITPLGDSNGLSPLCAIGLWTDISARILKLPSFELLHKEMLGGEIIPRSILMTTFESSHYLLCALGDGALFYFGLNIETGLLSDRKKVTLGTQPTVLRTFRSLSTTNVFACSDRPTVIYSSNHKLVFSNVNLKEVNYMCPLNSDGYPDSLALANNSTLTIGTIDEIQKLHIRTVPLYESPRKICYQEVSQCFGVLSSRIEVQDTSGGTTALRPSASTQALSSSVSSSKLFSSSTAPHETSFGEEVEVHNLLIIDQHTFEVLHAHQFLQNEYALSLVSCKLGKDPNTYFIVGTAMVYPEEAEPKQGRIVVFQYSDGKLQTVAEKEVKGAVYSMVEFNGKLLASINSTVRLYEWTTEKELRTECNHYNNIMALYLKTKGDFILVGDLMRSVLLLAYKPMEGNFEEIARDFNPNWMSAVEILDDDNFLGAENAFNLFVCQKDSAATTDEERQHLQEVGLFHLGEFVNVFCHGSLVMQNLGETSTPTQGSVLFGTVNGMIGLVTSLSESWYNLLLDMQNRLNKVIKSVGKIEHSFWRSFHTERKTEPATGFIDGDLIESFLDISRPKMQEVVANLQYDDGSGMKREATADDLIKVVEELTRIH
Background Information and Alternate Names
Species & domain architecture
An N-terminal helical bundle anchors DDB1; a central LON-like domain provides structural scaffolding; the C-terminal CULT module forms the conserved ligand pocket that binds thalidomide analogues.
UPS pathway role
The CRL4-CRBN E3 ligase (CUL4A/B–RBX1–DDB1–CRBN) selects lysine’s on substrates for ubiquitin transfer. Extensive research indicates that binding of immunomodulatory drugs (“IMiD’s”) remodels CRBN’s surface to recruit zinc-finger transcription factors (IKZF1/3, ZNF91), kinases (CK1α) and translation factors (GSPT1). Substrates that are bound by CRBN only in the presence of IMiD’s are known as “neo-substrates.”
Relevance to TPD & disease biology
IMiD anti-myeloma drugs, next-generation CELMoDs (iberdomide, mezigdomide) and SuFEx-diversified CRBN ligands leverage this switchable selectivity for targeted protein degradation, while germ-line loss-of-function mutations cause autosomal-recessive intellectual-development disorder. Expanding CRBN’s neo-substrate scope remains a frontier for oncology and neuro-degeneration research.
References
Liu Y., Bai J., Li D., et al. (2025) Trends Biochem Sci. 50 (2): 134-142. PMID 39753433
Carter T.R., et al. (2024) Bioorg Med Chem. 104: 117699. PMID 38608634
Costacurta M., et al. (2024) FEBS J. 291 (22): 4892-4912 PMID 38975872
Federspiel J.D., et al. (2024) Mol Cell Proteomics 23 (7): 100797 PMID 38866076
Kroupova A., et al. (2024) Nat Commun. 15: 8885. PMID 39406745
