Recombinant Human Fizzy-related protein homolog (FZR1)

Code CSB-EP892473HU
MSDS
Size $224
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP892473HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) FZR1.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP892473HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) FZR1.
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Product Details

Purity
Greater than 90% as determined by SDS-PAGE.
Target Names
FZR1
Uniprot No.
Research Area
Cell Biology
Alternative Names
CDC20 like 1b; CDC20 like protein 1; CDC20-like protein 1; CDC20C; CDH1; Cdh1/Hct1 homolog; Fizzy related protein 1; Fizzy related protein; Fizzy related protein homolog; Fizzy-related protein homolog; Fizzy/cell division cycle 20 related 1; FYR; FZR 1; FZR 2; Fzr; FZR_HUMAN; Fzr1; Fzr1 protein; FZR2; HCDH 1; HCDH; hCDH1; KIAA1242
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1-493aa
Target Protein Sequence
MDQDYERRLLRQIVIQNENTMPRVTEMRRTLTPASSPVSSPSKHGDRFIPSRAGANWSVNFHRINENEKSPSQNRKAKDATSDNGKDGLAYSALLKNELLGAGIEKVQDPQTEDRRLQPSTPEKKGLFTYSLSTKRSSPDDGNDVSPYSLSPVSNKSQKLLRSPRKPTRKISKIPFKVLDAPELQDDFYLNLVDWSSLNVLSVGLGTCVYLWSACTSQVTRLCDLSVEGDSVTSVGWSERGNLVAVGTHKGFVQIWDAAAGKKLSMLEGHTARVGALAWNAEQLSSGSRDRMILQRDIRTPPLQSERRLQGHRQEVCGLKWSTDHQLLASGGNDNKLLVWNHSSLSPVQQYTEHLAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTLTGQPLQCIDTGSQVCNLAWSKHANELVSTHGYSQNQILVWKYPSLTQVAKLTGHSYRVLYLAMSPDGEAIVTGAGDETLRFWNVFSKTRSTKESVSVLNLFTRIR
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
70.8kDa
Protein Length
Full Length of Isoform 2
Tag Info
N-terminal 6xHis-SUMO-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
Tris-based buffer,50% glycerol
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
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
Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
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.

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Target Background

Function
Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR).
Gene References into Functions
  1. Cdh1-dependent degradation of FoxM1 is required to shut down transcriptional activation of mitotic regulators during exit from mitosis. PMID: 18758239
  2. Cdh1 reciprocally regulates the Rb pathway through competing with E2F1 to bind the hypophosphorylated form of Rb. PMID: 19477924
  3. Data report that a nuclear-localized portion of the stress-activated kinase JNK is degraded by the APC/C(Cdh1) during exit from mitosis and the G1 phase of the cell cycle. PMID: 20581839
  4. We identified the known APC/C regulator Cdh1 and the F-box protein Fbxl15 as specific modulators of N-cyclin B1-luciferase steady-state levels and turnover. Collectively, our studies suggest that analyzing the steady-state levels of luciferase fusion proteins in parallel facilitates identification of specific regulators of protein turnover. PMID: 28296622
  5. Findings document the differential expression, subcellular localization and cell-cycle-regulatory activity of alternatively spliced human CDH1 isoforms. PMID: 12797865
  6. upon infection of quiescent cells human cytomegalovirus not only activates the E2F-dependent G(1)/S transcription program but also facilitates protein accumulation of APC/C substrates by rapid Cdh1 dissociation PMID: 16138013
  7. Cell cycle regulation of Six1 occurs both transcriptionally and post-translationally via phosphorylation PMID: 17130831
  8. Cdh1 may act as an important component in tumor suppression and could be considered as a novel biomarker in breast cancer. PMID: 18381934
  9. Reduced Cdh1 levels have no effect on destruction of many APC/C substrates during mitotic exit but strongly and specifically stabilize Aurora kinases. PMID: 18976910
  10. Low Cdh1 expression is associated with breast cancer. PMID: 19350629
  11. Glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1. PMID: 20080744
  12. DDB1 modulates the function of APC/C(Cdh1) in a manner independent of the Cul4-DDB1 complex PMID: 20395298
  13. Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress PMID: 20424596
  14. APC/CCdh1 is a master G0/G1 regulator and involved in differentiation and development processes. (Review) PMID: 21497201
  15. The deubiquitinase USP37 binds CDH1 and removes degradative polyubiquitin from cyclin A. USP37 was induced by E2F factors in G1, peaked at G1/S, and was degraded in late mitosis. Phosphorylation of USP37 by CDK2 stimulated its full activity. PMID: 21596315
  16. Ect2 is subject to proteasomal degradation after mitosis, following ubiquitination by the APC/C complex and its co-activator Cdh1 PMID: 21886810
  17. studies uncover a cell-cycle-independent function of Cdh1, establishing Cdh1 as an upstream component that governs Smurf1 activity PMID: 22152476
  18. In senescent cells, the DNA damage response induces proteasomal degradation of G9a and GLP, histone methyltransferases, through Cdc14B- and p21(Waf1/Cip1)-dependent activation of APC/C(Cdh1) ubiquitin ligase. PMID: 22178396
  19. APC/CCdh1 is able to ubiquitylate E2F3A in vitro, and that the degradation of E2F3A is stimulated by Cdh1, but not by Cdc20. PMID: 22580460
  20. The effect of Cdh1 on E2F1 degradation is blocked upon DNA damage. PMID: 22580462
  21. show that the Gas2l3 protein is targeted for ubiquitin-mediated proteolysis by the APC/C(Cdh1) complex, but not by the APC/C(Cdc20) complex, and is phosphorylated by Cdk1 in mitosis PMID: 23469016
  22. Data indicate that regulation of Rad17 turnover is through the Cdh1/anaphase-promoting complex pathway in breast cancer cells. PMID: 23637229
  23. NEDL2 is a novel substrate of APC/C-Cdh1 as cells exit mitosis and functions as a regulator of the metaphase to anaphase transition PMID: 24163370
  24. Results showed evidence that Wip1 underwent Cdh1-dependent proteolysis during mitosis and sustained Wip1 activity during mitosis, resulting in mitotic delay at the metaphase to anaphase transition. PMID: 25649870
  25. Using biochemistry and live cell imaging of single cells authors found that Cdh1 knockdown (kd) leads to strong nuclear stabilization of the substrates cyclin A and B and deregulated kinetics of DNA replication. PMID: 26455319
  26. Low Cdh1 expression may be important in AML biology by contributing to the differentiation block and response to therapy depending on differences in the microenvironment and the additional genetic background. PMID: 27374082
  27. APC/C(Cdc20), and APC/C(Cdh1) act successively to ensure that the disappearance of licensing inhibitors coincides exactly with a peak of Cdt1 and Cdc6. PMID: 23775192
  28. The Cells lacking Cdh1 have been shown to accumulate deoxyribonucleic acid (DNA) damage, suggesting that it may play a previously unrecognized role in maintaining genomic stability. PMID: 21768287
  29. APC/C(Cdc20) or APC/C(Cdh1) complexes regulate RAP80 stability during mitosis to the G(1) phase, and these events are critical for a novel function of RAP80 in mitotic progression. PMID: 22426463
  30. the sequential actions of the APC-c(Cdc20) and APC-c(Cdh1) ubiquitin ligases regulate the clearance of Mps1 levels and are critical for Mps1 functions during the cell cycle in human cells. PMID: 20729194
  31. Study shows that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex. PMID: 21241890
  32. APC-Cdh1 establishes a stimulus-response relationship that promotes S phase. PMID: 24356446
  33. The levels of CDC20 and CylinB1 increased and the levels of Ku70 and APC3 decreased after irradiation. APC/C(Cdh1) is involved in regulation of radiosensitivity in human NPC CNE-1 cells. PMID: 28004426
  34. Data show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents PMID: 27655696
  35. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. PMID: 27402801
  36. FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APC(FZR1) E3 ligase activity PMID: 28174173
  37. These findings identify a dynamic interplay between FZR1 and BRAF with strong implications for cell-fate determination and the tumor suppressor role of FZR1 PMID: 28373167
  38. results suggest that reduction of FZR1 increases therapeutic sensitivity of B-ALL and that transient rather than tonic inhibition of FZR1 may be a therapeutic strategy. PMID: 28143883
  39. results define a new APC/C(Cdh1) function that prevents cell cycle resumption after prolonged replication stress by inhibiting origin firing, which may act as an additional mechanism in safeguarding genome integrity. PMID: 26939887
  40. APC(Cdh1) inactivation is the commitment point when cells lose the ability to return to quiescence and decide to progress through the cell cycle. PMID: 27368103
  41. Data show that CDC20 homolog 1 (Cdh1) is O-GlcNAcylated in cultured cells. PMID: 27080259
  42. Anaphase-promoting complex/cyclosome-CDH1, rather than Cdc20, promotes the degradation of BRSK2 in vivo. PMID: 23029325
  43. Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. PMID: 20921411
  44. Cdh1-depleted HeLa cells reduced stress fiber formation significantly. The GTP-bound active Rho protein was apparently decreased in the Cdh1-depleted cells. PMID: 20530197
  45. FZR1 is not required for the completion of mitosis, but is an important regulator of G1 phase and is required for efficient DNA replication in human and mouse somatic cells. PMID: 19861496
  46. Destruction-box specificities of APC/C(fzy) and APC/C(fzr)& successive activation of APC/C by fzy & fzr establish the temporal substrate degradation pattern, explaining why some endogenous RXXL substrates are degraded by fzy & others by fzr complexes. PMID: 12198152
  47. Results indicate that Cdh1 mediates its own degradation by activating the anaphase-promoting complex/cyclosome to degrade itself. PMID: 15029244
  48. Retinoic acid downregulates Rae1, hence facilitating APC(Cdh1)-mediated Skp2 degradation leading to the arrest of cell cycle progression and neuroblastoma differentiation. PMID: 18212744
  49. during endocycles, APC/C Fzr/Cdh1 functions to reduce the levels of the mitotic cyclins and Geminin in order to facilitate the relicensing of DNA replication origins and cell cycle progression PMID: 18321983
  50. In response to genotoxic stress in G2, the phosphatase Cdc14B translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase APC/C(Cdh1), with the consequent degradation of Plk1, a prominent mitotic kinase. PMID: 18662541

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Subcellular Location
[Isoform 2]: Nucleus.; [Isoform 3]: Cytoplasm.
Protein Families
WD repeat CDC20/Fizzy family
Tissue Specificity
Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines whereas isoform 3 is expressed only at low levels in these tissues.
Database Links

HGNC: 24824

OMIM: 603619

KEGG: hsa:51343

STRING: 9606.ENSP00000378529

UniGene: Hs.413133

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