Recombinant Human E3 ubiquitin-protein ligase UHRF1 (UHRF1)

Code CSB-YP847229HU
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Source Yeast
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Code CSB-EP847229HU
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Source E.coli
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Code CSB-EP847229HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP847229HU
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Source Baculovirus
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Code CSB-MP847229HU
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Source Mammalian cell
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Product Details

Purity
>85% (SDS-PAGE)
Target Names
UHRF1
Uniprot No.
Alternative Names
Ac2-121; AL022808; E3 ubiquitin-protein ligase UHRF1; EC 6.3.2.-; FLJ21925; hNP95; hUHRF1; HuNp95; ICBP90; Inverted CCAAT box binding protein of 90 kDa; Inverted CCAAT box binding protein, 90-kD; Inverted CCAAT box-binding protein of 90 kDa; Liver regeneration-related protein LRRG126; MGC138707; NP95; Nuclear phosphoprotein 95; Nuclear phosphoprotein, 95-KD; Nuclear protein 95; Nuclear zinc finger protein Np95; RING finger protein 106; RNF106; TDRD22; Transcription factor ICBP90; Ubiquitin like containing PHD and RING finger domains protein 1; Ubiquitin like PHD and RING finger domain containing protein 1; Ubiquitin-like PHD and RING finger domain-containing protein 1; Ubiquitin-like protein containing PHD and RING finger domains 1; Ubiquitin-like with PHD and ring finger domains 1; Ubiquitin-like, containing PHD and RING finger domains, 1; Ubiquitin-like-containing PHD and RING finger domains protein 1; UHRF1; UHRF1_HUMAN
Species
Homo sapiens (Human)
Expression Region
1-793
Target Protein Sequence
MWIQVRTMDG RQTHTVDSLS RLTKVEELRR KIQELFHVEP GLQRLFYRGK QMEDGHTLFD YEVRLNDTIQ LLVRQSLVLP HSTKERDSEL SDTDSGCCLG QSESDKSSTH GEAAAETDSR PADEDMWDET ELGLYKVNEY VDARDTNMGA WFEAQVVRVT RKAPSRDEPC SSTSRPALEE DVIYHVKYDD YPENGVVQMN SRDVRARART IIKWQDLEVG QVVMLNYNPD NPKERGFWYD AEISRKRETR TARELYANVV LGDDSLNDCR IIFVDEVFKI ERPGEGSPMV DNPMRRKSGP SCKHCKDDVN RLCRVCACHL CGGRQDPDKQ LMCDECDMAF HIYCLDPPLS SVPSEDEWYC PECRNDASEV VLAGERLRES KKKAKMASAT SSSQRDWGKG MACVGRTKEC TIVPSNHYGP IPGIPVGTMW RFRVQVSESG VHRPHVAGIH GRSNDGAYSL VLAGGYEDDV DHGNFFTYTG SGGRDLSGNK RTAEQSCDQK LTNTNRALAL NCFAPINDQE GAEAKDWRSG KPVRVVRNVK GGKNSKYAPA EGNRYDGIYK VVKYWPEKGK SGFLVWRYLL RRDDDEPGPW TKEGKDRIKK LGLTMQYPEG YLEALANRER EKENSKREEE EQQEGGFASP RTGKGKWKRK SAGGGPSRAG SPRRTSKKTK VEPYSLTAQQ SSLIREDKSN AKLWNEVLAS LKDRPASGSP FQLFLSKVEE TFQCICCQEL VFRPITTVCQ HNVCKDCLDR SFRAQVFSCP ACRYDLGRSY AMQVNQPLQT VLNQLFPGYG NGR
Protein Length
full length protein
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
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 before Lyophilization
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℃/-80℃. 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
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
Please contact us to get it.

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Target Background

Function
Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF1 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation.
Gene References into Functions
  1. Our novel findings strongly indicate that inactivation of the Notch signaling pathway impedes hepatocellular carcinoma progress via reduction of ICBP90. PMID: 30309512
  2. Using an integrative approach that combines small angle X-ray scattering, NMR spectroscopy, and molecular dynamics simulations, we characterized the dynamics of the tandem tudor domain-plant homeodomain (TTD-PHD) histone reader module, including its 20-residue interdomain linker. PMID: 29074623
  3. UHRF1 deficiency leads to the induction of EMT by activating the CXCR4/AKT-JNK/IL-6 signaling pathway, thereby contributing to the expansion of cancer stem-like cells PMID: 28584306
  4. studies support a noncompetitive model for UHRF1 and DNMT1 chromatin recruitment to replicating chromatin and define a role for hemimethylated linker DNA as a regulator of UHRF1 ubiquitin ligase substrate selectivity. PMID: 30104358
  5. Lys4 methylation on H3 peptide has an insignificant effect on combinatorial recognition of R2 and K9me2 on H3 by the UHRF1 TTD-PHD. We propose that subtle variations of key residues at the binding pocket determine status specific recognition of histone methyl-lysines by the reader domains. PMID: 29656054
  6. Study provides evidence that elevated expression of UHRF1 plays an important role in melanoma cell proliferation and progression, and it can be used as a prognostic biomarker for melanoma. PMID: 29620240
  7. The emodininduced downregulation of UHRF1 led to an increase in the level of DNA methyltransferase 3A. PMID: 28901428
  8. Findings confirmed that UHRF1 is a gene driver in medulloblastoma (MB) and, revealed that UHRF1 is in a modulation axis downstream of miR-378. Its promoter region is targeted by miR-378 which negatively regulates its expression in MB cells. PMID: 28901497
  9. UHRF1 controls both CDH1 and antisense-directed non coding RNA RCDH1-AS by directly binding this bidirectional promoter region. PMID: 29466696
  10. Epigenetic enhancement of the post-replicative DNA mismatch repair of mammalian genomes by a Hemi-(m)CpG-Np95-Dnmt1 axis has been demonstrated for humans and mice. PMID: 27886214
  11. These results suggest that tumor-promoting functions of UHRF1 in retinoblastoma are largely independent of its role in DNA methylation. PMID: 28467809
  12. UHRF1 is a key epigenetic regulator of DNA methylation in esophageal squamous cell carcinoma and might be a potential target for cancer treatment PMID: 27507047
  13. Elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in hepatocellular carcinoma. PMID: 28060737
  14. Results find the overexpression of the anti-apoptotic UHRF1 to coordinate the epigenetic silencing of several tumor suppressor genes in many human haematological and solid cancers causing apoptosis inhibition. [review] PMID: 27839516
  15. our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in bladder cancer cells by regulating UHRF1 PMID: 27072587
  16. The results indicated that globular adiponectin inhibited the prooncogenic effects of leptin via AdipoR2-mediated suppression of UHRF1 PMID: 28285359
  17. Hemi-methylated CpGs DNA recognition activates UHRF1 ubiquitylation towards multiple lysines on the H3 tail adjacent to the UHRF1 histone-binding site. PMID: 27595565
  18. Down-regulation of UHRF1 is an important mechanism of PIM1-mediated cellular senescence. PMID: 28394343
  19. UHRF1 gene expression levels correlates with the major pathological characteristics of transitional cell carcinoma samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer. PMID: 28128913
  20. decreased UHRF1 expression is a key initial event in the suppression of DNMT1-mediated DNA methylation and in the consequent induction of senescence via increasing WNT5A expression PMID: 28100769
  21. Our results provide insights into the molecular basis of DNMT1 dysfunction in hereditary sensory and autonomic neuropathies with dementia and hearing loss patients and emphasize the importance of the TS domain in the regulation of DNA methylation in pluripotent and differentiating cells PMID: 28334952
  22. results identify UHRF1 as a novel HSP90 client protein and shed light on the regulation of UHRF1 stability and function. PMID: 27489107
  23. Down-regulation of UHRF1 by RNAi inhibited proliferation and clonogenic ability of medullobastoma cell lines with cell cycle arrest in G1/G2-phase. Cells transfected with lenti-shUHRF1 showed increased p16 expression and location shift of CDK4 in medulloblastoma cells. PMID: 27449774
  24. Our study uncovered that UHRF1 overexpressed in cervical squamous cell carcinoma and silent UHRF1 gene can reduce tumorigenicity of the CaSki cells by decreasing its proliferation capacity and making it stagnate at G0 and G1 phases as well as accelerating its apoptosis PMID: 27431502
  25. The overexpression of UHRF1 was correlated with the stage and grade of gastric cancer and is associated with the genotype distribution of MiR-146a rs2910164. PMID: 26896831
  26. Studies indicate that ubiquitin like with PHD and ring finger domains 1 protein (UHRF1) interacts with DNA interstrand crosslinks (ICLs) both in vitro and in vivo. PMID: 26700964
  27. Results showed that UHRF1 was overexpressed in almost all of the prostate cancer cell (PCa) lines. Its expression levels were correlated with some clinical features of PCa suggesting it as an independent prognostic factor for biochemical recurrence. PMID: 26884069
  28. UHRF1 promotes osteosarcoma cell invasion by downregulating the expression of Ecadherin and increasing epithelialtomesenchymal transition in an Rb1dependent manner. PMID: 26548607
  29. Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its H3 histone recognition. PMID: 27045799
  30. UHRF1 was over-expressed in hepatocellular carcinoma tissues compared to the adjacent normal tissues and UHRF1 expression shared significant relevance with distant metastasis, cancer area and HBV. PMID: 26464697
  31. results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer PMID: 26768845
  32. These findings identify ICBP90 as a key regulator of MIF transcription and provide functional insight into the regulation of the polymorphic MIF locus. PMID: 26752645
  33. miR-124 could control the fate of target gene UHRF1 mRNA by binding 3'-UTR PMID: 26310391
  34. This study showed that UHRF1 interacts directly with BRCA1 and is involved in DNA double-strand break repair. PMID: 26727879
  35. Findings demonstrated the inhibitory effect of MEG3 in vivo and vitro and illuminated that MEG3 could be a potential biomarker for the survival of hepatocellular carcinoma (HCC) patients. Its expression seemed to be regulated by UHRF1 in HCC. PMID: 25641194
  36. K-Ras drives UHRF1 expression, establishing a novel link between this oncogene and Nrf2-mediated cellular protection. PMID: 26497117
  37. UHRF1 is overexpressed in serum and gastric tissue of stomach cancer patients. PMID: 26161699
  38. The downregulation of UHRF1 by Torin-1 was partially due to a decrease in the UHRF1 mRNA level. Torin-2 effectively inhibited hepatocellular carcinoma cell proliferation through induction of autophagy PMID: 26239364
  39. UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation. PMID: 26147747
  40. UHRF1 could act as a new oncogenic factor in ovarian cancer and be a potential molecular target for ovarian cancer gene therapy. PMID: 26070868
  41. UHRF1 promotes recruitment of lesion-processing activities via its affinity to recognize DNA damage PMID: 25818288
  42. describe a mechanism of interstrand crosslink (ICL) sensing and propose that UHRF1 is a critical factor that binds to ICLs. In turn, this binding is necessary for the subsequent recruitment of FANCD2, which allows the DNA repair process to initiate PMID: 25801034
  43. results are consistent with a "reader" role, in which the SRA domain scans DNA sequences for hemimethylated CpG sites without perturbation of the structure of contacted nucleotides. PMID: 26368281
  44. High UHRF1 expression is associated with ovarian cancer. PMID: 25743796
  45. The global DNA hypomethylation induced by the DNMT1/PCNA/UHRF1 disruption is an oncogenic event of human tumorigenesis. PMID: 24637615
  46. miR-9 could repress the expression of UHRF1, and function as a tumor-suppressive microRNA in colorectal cancer. PMID: 25940709
  47. UHRF1 may play a pivotal role in suppressing the malignant alteration of cancer cells. PMID: 25572953
  48. Promoter hypermethylation and down-expression of let-7a-3 may play a role in DN by targeting UHRF1. PMID: 26049093
  49. UHRF1 regulates p53 ubiquitination and p53-dependent cell apoptosis in clear cell renal cell carcinoma. PMID: 26102039
  50. our study demonstrated that UHRF1 played an oncogenic role in the progression of pancreatic cancer, and UHRF1 might be a promising target for the treatment of pancreatic cancer. PMID: 25416862

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Involvement in disease
Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression.
Subcellular Location
Nucleus. Note=Localizes to replication foci. Enriched in pericentric heterochromatin. Also localizes to euchromatic regions.
Tissue Specificity
Expressed in thymus, bone marrow, testis, lung and heart. Overexpressed in breast cancer.
Database Links

HGNC: 12556

OMIM: 607990

KEGG: hsa:29128

UniGene: Hs.108106

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