Recombinant Human Protein cereblon(CRBN)

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Code CSB-BP842761HU
Size US$1888Purchase it in Cusabio online store
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Description

The gene fragment corresponding to the 1-442aa of the human CRBN protein was synthesized, with appropriate restriction sites suitable for in-frame cloning into an expression vector, with C-terminal 9xHis tag. The Baculovirus was transformed with the expression vector, and the clone was expressed upon certain induction. After the induced cell centrifugation, the recombinant protein was purified from the cell extract and presented as C-terminal 9xHis-tagged fusion. This recombinant human CRBN protein's purity is greater than 85% assayed by SDS-PAGE. The CRBN protein ran to a band of about 56 kDa molecular weight on the gel, indicating a glycosylated form of the protein.

Cereblon (CRBN) is a common direct target of thalidomide and related compounds and works as a Cullin Ring 4 E3 ubiquitin ligase (CRL4) with DDB1, CUL4, and ROC1. CRBN the molecular target of lenalidomide and pomalidomide, is a substrate receptor of the cullin ring E 3 ubiquitin ligase complex, CRL 4 CRBN. In early reports, Researchers identifed that a novel cereblon modulator recruits GSPT1 to the CRL4-CRBN ubiquitin ligase. The substrate specificity of CRL4CRBN is modulated by thalidomide-related compounds. Ablation ofCRBNinduces loss of type I collagen and SCH in mouse skin by fibroblast senescence via the p38 MAPK pathway. The CRBN, CUL4A and DDB1 expression predicts the response to immunomodulatory drugs and survival of multiple myeloma patients. Cereblon modulator CC-885 inducesCRBN-dependent ubiquitination and degradation of CDK4 in multiple myeloma.

Purity Greater than 85% as determined by SDS-PAGE.
Target Names CRBN
Uniprot No. Q96SW2
Research Area Neuroscience
Alternative Names CRBN; AD-006; Protein cereblon
Species Homo sapiens (Human)
Source Baculovirus
Expression Region 1-442aa
Target Protein Sequence MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 52.5 kDa
Protein Length Full Length
Tag Info C-terminal 9xHis-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time 3-7 business days
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

Customer Reviews and Q&A

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 Q&A
Q:

Does it exist in its properly folded state such that it is biologically active? What buffer is being used?

A:
Thanks for your inquiry.1. We haven't tested the activity of this protein. This protein has been ordered for more than 10 times but we haven't received any feedback about the activity yet.
This literature mentions co-expression using the BP system and the expressed protein is used in subsequent studies.
(Recombinant baculovirus of ZZ-His-CRBN and DDB1-StrepTag (ST) were generated and amplified using Bac-to-Bac baculovirus expression system from Invitrogen in Sf9 insect cells.
ZZ-His-CRBN and DDB1-ST were co-expressed in High Five (Tni) insect in 10L wave bags at 27 ºC using un-supplemented ESF921 media from Expression Systems. )
Here is the link of the literature: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496085/
The protein we provide is full length and the expression host used by BP system is Sf9, meanwhile, this protein is purified under mild conditions, which should have activity in theory.
2. Our default storage buffer is Tris-based buffer, 50% glycerol. If you have special requirement for the storage buffer, please tell us and we will try to satisfy.
Q:

I have one more questions about CSB-BP842761HU protein.
What is the concentration of the remaining 90ug product?

A:
Thanks for your inquiry. The 90ug stock protein is liquid form, concentration 0.1mg/ml.
Buffer: 0.2 μm sterile filtered 20 mM Tris-HCl,0.5M NaCl,pH 8.0,50%glycerol

Target Background

Function
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 (Probable). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1. May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism.
Gene References into Functions
  1. mitochondrially expressed CRBN exhibited protease activity, and was induced by oxidative stress. PMID: 27417535
  2. We sequenced CRBN-thalidomide binding region in 38 thalidomide embryopathy individuals and 136 Brazilians without congenital anomalies, and performed in silico analyses. Eight variants were identified, seven intronic and one in 3'UTR. PMID: 27751757
  3. These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to Autosomal-recessive non-syndromic intellectual disability (ARNS-ID)and provide new insight into genotype-phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. PMID: 28143899
  4. CRBN expression is of prognostic value in MM patients ineligible for ASCT treated with thalidomide as an immunomodulatory drug. With low expression indicating a possible suboptimal treatment outcome, measurement of CRBN expression might serve as additional prognostic tool in the personalized treatment approach. PMID: 27618360
  5. Plasmablast differentiation, whether induced by BAFF or CD40L, is prevented by modulation of CRBN activity with CC-220, which induces degradation of the B cell differentiation factors Aiolos and Ikaros. Downregulation of these B cell differentiation processes by CC-220 modulation of CRBN provides a new therapeutic approach to treating B cell-mediated pathology in SLE. PMID: 28848067
  6. High CRBN expression is associated with multiple myeloma. PMID: 28017969
  7. CRBN negatively regulates TLR4 signaling via attenuation of TRAF6 and TAB2 ubiquitination. PMID: 27468689
  8. Compared with newly diagnosed multiple myeloma, an increased prevalence of mutations in the Ras pathway genes KRAS, NRAS, and/or BRAF (72%), as well as TP53 (26%), CRBN (12%), and CRBN pathway genes (10%) was observed. PMID: 27458004
  9. dual assay demonstrated superior Cereblon IHC measurement in MM samples compared with the single IHC assay using a published commercial rabbit polyclonal Cereblon antibody and could be used to explore the potential utility of Cereblon as a biomarker in the clinic PMID: 26186254
  10. IRF4 and CRBN polymorphisms affect risk and response to treatment in multiple myeloma PMID: 28083618
  11. overview of the current understanding of mechanism of action of Immunomodulatory drugs via CRBN and prospects for the development of new drugs that degrade protein of interest. PMID: 27460676
  12. 45.2 of multiple myeloma patients were CRBN(+). Among patients treated with thalidomide-based regimens, CRBN(+) patients showed a better treatment response than did CRBN-negative patients. There was no significant difference in survival outcomes between thalidomide- and bortezomib-based regimens in CRBN(+) patients. PMID: 27365142
  13. GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. PMID: 26990986
  14. Structural dynamics of the cereblon ligand binding domain. PMID: 26024445
  15. Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels. PMID: 26021757
  16. Data suggest that cereblon (CRBN) expression in peripheral blood chronic lymphocytic leukemia (CLL) cells is independent of prognostic factors and may be considered a potential biomarker. PMID: 24925210
  17. High levels of full-length CRBN mRNA in lower risk 5q deletion patients are necessary for the efficacy of lenalidomide. PMID: 25284710
  18. A copy number gain of CRBN gene might be responsible for developmental delay/intellectual disability. PMID: 25858704
  19. Although abnormal CRBN function may be associated with intellectual disability disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. PMID: 26188093
  20. Studied the protein cereblon , which has been recently indentified as a primary target of thalidomide and its C-terminal part as responsible for binding thalidomide within a domain carrying several invariant cysteine and tryptophan residues. PMID: 25569776
  21. The study presents the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide. PMID: 25108355
  22. structures of the DDB1-CRBN complex bound to thalidomide, lenalidomide and pomalidomide PMID: 25043012
  23. CRBN expression in bone marrow myeloma cells is associated with superior treatment response to lenalidomide in refractory myeloma and thalidomide/dexamethasone in new patients. CRBN is a crucial factor for the anti-MM effect of immunomodulators. PMID: 24687382
  24. CRBN expression may provide a biomarker to predict response to Immunomodulatory drugs in patients with MM and its high expression can serve as a marker of good prognosis. PMID: 24118365
  25. CRBN and IRF4 have been shown to be associated with response to lenalidomide in patients, these findings do not translate back to HMCLs, which could be attributable to factors present in the bone marrow microenvironment. PMID: 23992230
  26. In the three intrinsically IMiD-resistant cell lines that clearly express detectable levels of cereblon, the absence of CRBN and DDB1 mutations suggest that potential cereblon-independent mechanisms of resistance exist PMID: 24166296
  27. Presents a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4(CRBN) , leading to their ubiquitination, subsequent proteasomal degradation and T cell activation. PMID: 24328678
  28. Data indicate that low cereblon (CRBN) expression can predict resistance to immunomodulatory drug (IMiD monotherapy and is a predictive biomarker for survival outcomes. PMID: 24129344
  29. Findings suggest an approach for the treatment of mental retardation associated with cereblon nonsense mutation. PMID: 23983124
  30. We investigated the role of CRBN in response to lenalidomide in myelodysplastic syndrome infants without chromosome 5 deletion. PMID: 23434730
  31. We conclude that CRBN expression may be associated with the clinical efficacy of thalidomide. PMID: 23233657
  32. These findings suggest that CRBN may modulate proteasome activity by directly interacting with the beta7 subunit. PMID: 23026050
  33. Data show that in a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNbeta production. PMID: 22698399
  34. CRBN is an essential requirement for immunoregulatory drugs activity and a possible biomarker for the clinical assessment of antimyeloma efficacy. PMID: 21860026
  35. CRBN directly interacts with the alpha1 subunit of AMP-activated protein kinase (AMPK alpha1) and inhibits the activation of AMPK activation. PMID: 21232561
  36. The results suggest that mutCRBN may cause ARNSID by disrupting the developmental regulation of BK(Ca) in brain regions that are critical for memory and learning. PMID: 20131966
  37. A nonsense mutation causing a premature stop codon in CRBN was found in a large kindred with mild mental retardation. ATP-dependent degradation of proteins may play a role in memory and learning. PMID: 15557513
  38. This may suggest new functions of CRBN in cell nucleolus besides its mitochondria protease activity in cytoplasm. PMID: 17380424
  39. Nonsense mutation (R419X) CRBN disturbs the development of adult brain BK(Ca) isoforms. These changes are predicted to result in BK(Ca) channels with a higher intracellular Ca(2+) sensitivity, faster activation, and slower deactivation kinetics. PMID: 18414909

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Involvement in disease Mental retardation, autosomal recessive 2A (MRT2A)
Subcellular Location Cytoplasm. Nucleus. Membrane; Peripheral membrane protein.
Protein Families CRBN family
Tissue Specificity Widely expressed. Highly expressed in brain.
Database Links

HGNC: 30185

OMIM: 607417

KEGG: hsa:51185

STRING: 9606.ENSP00000231948

UniGene: Hs.18925

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