CUL3 Recombinant Monoclonal Antibody

Code CSB-RA898115A0HU
Size US$210
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  • IHC image of CSB-RA898115A0HU diluted at 1:100 and staining in paraffin-embedded human breast cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
  • IHC image of CSB-RA898115A0HU diluted at 1:100 and staining in paraffin-embedded human prostate cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
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Product Details

Uniprot No.
Target Names
CUL3
Alternative Names
Cullin-3 (CUL-3), CUL3, KIAA0617
Species Reactivity
Human
Immunogen
A synthesized peptide derived from human Cullin 3
Immunogen Species
Homo sapiens (Human)
Conjugate
Non-conjugated
Clonality
Monoclonal
Isotype
Rabbit IgG
Clone No.
7B6
Purification Method
Affinity-chromatography
Concentration
It differs from different batches. Please contact us to confirm it.
Buffer
Rabbit IgG in phosphate buffered saline, pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Liquid
Tested Applications
ELISA, IHC
Recommended Dilution
Application Recommended Dilution
IHC 1:50-1:200
Troubleshooting and FAQs
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
Lead Time
Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Description

CUL3 is a molecular scaffold of cullin 3-ring ubiquitin ligase (CRL3), which can be activated by covalent binding to NEDD8, a process called neddylation. CUL3, with the help of its various substrate recognition proteins, also known as adaptors containing BTB domains, recognizes specific substrates for ubiquitination and then executes proteasomal degradation. A reduction in CUL3 expression in vascular smooth muscle (VSM) causes abnormal vasoconstriction and hence hypertension. Recent studies have demonstrated that silencing CUL3 in the trophoblast cells leads to decreased trophoblast invasion and may contribute to the onset of preeclampsia (PE).

The recombinant CUL3 antibody was prepared by obtaining the antibody genes, cloning the genes into a plasma vector to construct vector clone, transfecting the vector clone into a mammalian cell line for transient expression, and purifying the antibody by Affinity-chromatography. This recombinant CUL3 antibody has been verified to detect the CUL3 protein from Human in the ELISA, IHC.

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Target Background

Function
Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4. The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway. The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis. The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity. The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry. The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1. By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation.
Gene References into Functions
  1. The CRL3 complexes evolved to fulfill a pivotal role in mammalian cell differentiation. PMID: 29249570
  2. Significantly mutated gene CUL3 displayed strong antiproliferation function in Esophageal Squamous Cell Carcinoma but not in Esophageal Adenocarcinomas. PMID: 28860350
  3. we demonstrated that cullin 3 plays a promoting role in the malignant progression of nasopharyngeal carcinoma PMID: 28429677
  4. our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with tumorigenesis and drug resistance in head and neck squamous cell cancer . PMID: 29306329
  5. CUL3 rs17479770 variant could be a protective factor in the pathogenesis of essential hypertension. PMID: 28804198
  6. Cullin 3 regulates ADAM17-mediated ectodomain shedding of AREG. PMID: 29550478
  7. CUL3 mutation is associated with Pseudohypoaldosteronism types II PMID: 28593901
  8. a loss of CULLIN3 represents a common signaling node for controlling the activity of intracellular WNT and SHH signaling pathways mediated by ID1 PMID: 27477274
  9. The roles of cullin 3-based ubiquitin E3 ligases as key players in the process of various signals in endothelial cell function and angiogenesis. PMID: 28981750
  10. Downregulation of Cul3 led to a marked increase in RhoA protein expression after 6 days of adipocytes differentiation, suggesting that Cul3 is involved in the regulation of RhoA stability. PMID: 28499918
  11. CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells PMID: 27664236
  12. this work identifies both calcium and CUL3 co-adaptors as important regulators of ubiquitylation events that control human development. PMID: 27716508
  13. Together, the data indicate that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and formation of multivesicular bodies by ubiquitinating and degrading EPS15 at endosomes. PMID: 27008177
  14. Data show that Cullin3 exerts its function through promoting breast-cancer metastasis suppressor 1 (BRMS1) protein degradation, which was associated with epithelial-mesenchymal transition (EMT), migration and invasion. PMID: 26544623
  15. CUL3 acts as a tumor suppressor by regulating oxidative stress PMID: 25995385
  16. The authors find that the KCTD proteins 5, 6, 9 and 17 bind to Cul3 with high affinity, while the KCTD proteins 1 and 16 do not have detectable binding. PMID: 26334369
  17. Data show that the differentiation of LiSa-2 preadipocytes is associated with an increase of cullin-associated and neddylation-dissociated 1 (CAND1), COP9 signalosome (CSN), neddylated cullin 3 (Cul3) and the BTB protein Keap1. PMID: 26219975
  18. Heterodimeric CUL3 proteinubiquitylates TIAM1.CUL3 regulates TIAM1 abundance and subsequent RAC1 signaling. PMID: 25684205
  19. these findings indicate that the designed stapled peptides can efficiently mimic protein-protein interactions and are potentially able to modulate fundamental biological processes involving Cul3. PMID: 25848797
  20. these results suggest an essential role for CUL3 in the invasion and migration of trophoblast cells, and dysregulation of its expression may be associated with the onset of pre-eclampsia PMID: 26021998
  21. The KCTD5/cullin3 complex stabilizes ZNF711 transcription factor.Formation of trimeric complexes of KCTD5/cullin3 with MCM7, ZNF711 and FAM193B. PMID: 26188516
  22. Cul3 deletion mutations (associated with hypertension), impair ubiquitin ligase activity toward RhoA. PMID: 26100637
  23. Studied the DNA-level mechanisms affecting KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex as a regulator of NRF2 levels in ovarian cancer. PMID: 25114896
  24. REVIEW: latest advances in basic research on the biology of Cul3 and how it could help to direct drug discovery efforts on this target PMID: 24024173
  25. Hyperkalemic hypertension-associated cul3 mutations depletes KLHL3, preventing WNK degradation, despite increased CUL3-mediated WNK ubiquitylation. PMID: 25250572
  26. This study identified a new set of Cul3-binding proteins known as CLWs via tandem affinity purification and LC/MS-MS analysis. PMID: 25011449
  27. data suggest a new paradigm for Hsp90-modulated assembly of a Cul3/DBC2 E3 ubiquitin ligase complex that may extend to other E3 ligase complexes. PMID: 24608665
  28. Regulation of WNK4 by CUL3 and its relationship to blood pressure regulation and electrolyte homeostasis. [Review] PMID: 24518042
  29. CUL3 and KLHL3 gene products are physiologically important regulators of thiazide-sensitive distal nephron sodium chloride reabsorption. PMID: 24266877
  30. CUL3/KLHL22 may contact two distinct motifs within PLK1 protein, consistent with the bivalent mode of substrate targeting. PMID: 24067371
  31. genetic analysis to detect the CUL3 mutation and to enable intervention early in the disease course would be beneficial for infants with suspected pseudohypoaldosteronism type II PMID: 23689903
  32. In a patient with pseudohypoaldosteronism type III, the Cullin 3 gene showed abnormal splicing caused by modification of exon 9. PMID: 23902721
  33. analysis of how mutations of KLHL3 show less ability to ubiquitinate WNK4 because of KLHL3's low stability and/or decreased binding to CUL3 or WNK4 PMID: 23962426
  34. Disease causing mutations in human KLHL3 disrupt the interaction with CUL3, a crystallographic study. PMID: 23573258
  35. Co-expression of KLHL2 and Cullin3 decreases the abundance of WNK1, WNK3 and WNK4 within HEK293T cells. PMID: 23838290
  36. CUL3 and KLHL3 have roles in in electrolyte homeostasis and in Pseudohypoaldosteronism type II PMID: 23576762
  37. Cul3 modulated the aggressive phenotype of cancer cells by modifying the expression of cytoskeleton proteins involved in bladder cancer aggressiveness. PMID: 23308193
  38. Somatic mutation in CUL3 gene is associated with sporadic form of papillary renal cell carcinoma. PMID: 23365135
  39. changes in conformation rather than dissociation from Cul3 inactivate the repressor function of Keap1 leading to Nrf2 stabilization PMID: 23454126
  40. analysis of crystal structures of the BTB-BACK domains of KLHL11 both alone and in complex with Cul3 PMID: 23349464
  41. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. PMID: 23387299
  42. these results demonstrate that KBTBD13 is a putative substrate adaptor for Cul3-RL that functions as a muscle specific ubiquitin ligase, and thereby implicate the ubiquitin proteasome pathway in the pathogenesis of KBTBD13-associated NEM. PMID: 22542517
  43. These results suggest a crucial role of Cul3 in regulating late steps in the endolysosomal trafficking pathway. PMID: 22219362
  44. fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis PMID: 22266938
  45. KLHL7 forms a dimer, assembles with Cul3 through its BTB and BACK domains, and exerts E3 activity. PMID: 21828050
  46. Nrf2 regulates Cul3-Rbx1 by controlling regulation of expression and induction of Cul3-Rbx1 PMID: 20452971
  47. Data show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2. PMID: 19768582
  48. KLHL20-Cul3-ROC1 is an E3 ligase for DAPK ubiquitination PMID: 20389280
  49. KLHL21 localizes to midzone microtubules in anaphase & recruits aurora B & Cul3 to this region; results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B PMID: 19995937
  50. Data show that Keap1 associates with the N-terminal region of Cullin 3 through the IVR domain and promotes the ubiquitination of Nrf2 in cooperation with the Cullin 3-Roc1 complex. PMID: 15282312

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Involvement in disease
Pseudohypoaldosteronism 2E (PHA2E)
Subcellular Location
Nucleus. Golgi apparatus. Cell projection, cilium, flagellum. Cytoplasm, cytoskeleton, spindle. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole.
Protein Families
Cullin family
Tissue Specificity
Brain, spermatozoa, and testis (at protein level). Widely expressed.
Database Links

HGNC: 2553

OMIM: 603136

KEGG: hsa:8452

STRING: 9606.ENSP00000264414

UniGene: Hs.372286

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