Recombinant Human E3 ubiquitin-protein ligase RNF168 (RNF168)

中文名稱：

人RNF168重組蛋白
貨號：

CSB-BP814236HU
規格：

￥3168
圖片：
(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
其他：

產品詳情
產品評價
相關產品
靶點詳情

產品詳情

純度：

Greater than 85% as determined by SDS-PAGE.
基因名：

RNF168
Uniprot No.：

Q8IYW5
別名：

(hRNF168)(RING finger protein 168)(RING-type E3 ubiquitin transferase RNF168)
種屬：

Homo sapiens (Human)
蛋白長度：

Full Length
來源：

Baculovirus
分子量：

66.6 kDa
表達區域：

1-571aa
氨基酸序列

MALPKDAIPSLSECQCGICMEILVEPVTLPCNHTLCKPCFQSTVEKASLCCPFCRRRVSSWTRYHTRRNSLVNVELWTIIQKHYPRECKLRASGQESEEVADDYQPVRLLSKPGELRREYEEEISKVAAERRASEEEENKASEEYIQRLLAEEEEEEKRQAEKRRRAMEEQLKSDEELARKLSIDINNFCEGSISASPLNSRKSDPVTPKSEKKSKNKQRNTGDIQKYLTPKSQFGSASHSEAVQEVRKDSVSKDIDSSDRKSPTGQDTEIEDMPTLSPQISLGVGEQGADSSIESPMPWLCACGAEWYHEGNVKTRPSNHGKELCVLSHERPKTRVPYSKETAVMPCGRTESGCAPTSGVTQTNGNNTGETENEESCLLISKEISKRKNQESSFEAVKDPCFSAKRRKVSPESSPDQEETEINFTQKLIDLEHLLFERHKQEEQDRLLALQLQKEVDKEQMVPNRQKGSPDEYHLRATSSPPDKVLNGQRKNPKDGNFKRQTHTKHPTPERGSRDKNRQVSLKMQLKQSVNRRKMPNSTRDHCKVSKSAHSLQPSISQKSVFQMFQRCTK
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.
蛋白標簽：

C-terminal 10xHis-tagged
產品提供形式：

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.
緩沖液：

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.
復溶：

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.
儲存條件：

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
保質期：

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.
貨期：

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
注意事項：

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.

產品評價

靶點詳情

功能：

E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
基因功能參考文獻：
1. Results suggest that RNF168 acts as a counterpart of PARP1 in DDR and regulates the HR/NHEJ repair processes through the ubiquitination of PARP1. PMID: 30037213
2. RNF168 interacts with TOP2alpha to mediate its polyubiquitylation and RNF168 deficiency confers resistance to ICRF-193, a TOP2 catalytic inhibitor, and cytotoxic anti-cancer drug etoposide in cultured human cancers cells. PMID: 27558965
3. Ub-interacting residues in UDM2 prevent the accumulation of RNF168 to double-strand breaks sites in U2OS cells, whereas those in UDM1 have little effect. PMID: 29330428
4. We identified 85 overlapping deletions, of which six included the RPL35A gene and all should be had Diamond-Blackfan anemia (DBA).we sequenced the remaining RNF168 gene and examined her fibroblast culture for a DNA double strand break repair deficiency. These results were normal, indicating that the immunodeficiency is unlikely to result from a RNF168 deficiency. PMID: 28432740
5. deregulated RNF168/53BP1 pathway could promote tumorigenesis by selecting for a more robust, better stress-adapted cancer cell phenotype, through altered DNA repair, fueling genomic instability and tumor heterogeneity PMID: 27841863
6. The association of RNF168 with PML NBs resulted in increased ubiquitylation. PMID: 26675234
7. Results reveal an important role of USP7 in regulating ubiquitin-dependent signaling via stabilization of RNF168. PMID: 25894431
8. CK2/WIP1-mediated modulation of LSD1 phosphorylation facilitates RNF168-dependent ubiquitination and recruitment of 53BP1 to the DNA damage sites. PMID: 25999347
9. The ubiquitin ligase RNF168 is strictly dependent on the activity that UbK27 is required to promote chromatin ubiquitination following DNA damage. PMID: 25578731
10. Finding that RNF8 is less abundant than RNF168 identifies RNF8 as a rate-limiting determinant of focal repair complex assembly PMID: 25304081
11. Depletion of RNF8 or RNF168 blocks the degradation of diffusely localized nuclear 53BP1. PMID: 25337968
12. The E3 ligase RNF168 promotes both H2A ubiquitylation and neddylation. RNF168 is itself a substrate for NEDD8, and neddylation of RNF168 is necessary for its E3 ubiquitin activity. PMID: 24634510
13. The acidic patch functions within the nucleosome as nucleosomes containing a mutated acidic patch exhibit defective H2A/H2AXub by RNF168 and RING1B/BMI1 in vitro PMID: 24603765
14. Taken together, the results suggested that USP3 is a negative regulator of ubiquitination signaling, counteracting RNF168- and RNF8-mediated ubiquitination PMID: 24196443
15. Before their localization to DNA double strand breaks, RNF168 interacts with 53BP1 and modifies it through the addition of a chain of ubiquitin-polypeptides. PMID: 24324146
16. RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. PMID: 24217620
17. study unveils a functional link between DNA damage-induced poly(ADP-ribosyl)ation, SMARCA5-mediated chromatin remodeling and RNF168-dependent signaling and repair of DSBs. PMID: 23264744
18. RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. PMID: 23525009
19. Unlike RNF8, RNF168 RING domain did not stably associate with UBC13 at double-stranded DNA breaks in vitro or in vivo. PMID: 23255131
20. RNF168 is important for defects in homologous recombination caused by loss of the BRCA1 in breast cancer cells. PMID: 23055523
21. Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. Study shows that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR. PMID: 22980979
22. Inactivation of K13 and K15 reduces RNF168- dependent ubiquitination of histones H2As, while inactivation of both N- and C-terminal sites completely abolishes histone ubiquitination. PMID: 22713238
23. RNF168, its paralog RNF169, RAD18, and the BRCA1-interacting RAP80 protein accumulate at DNA double strand break sites through the use of bipartite modules composed of ubiquitin binding domains. PMID: 22742833
24. Data show RING finger (RNF) E3 ubiquitin ligase RNF8 dimerizes and binds to E2 ubiquitin-conjugating complex Ubc13/Mms2 with formation of Lys-63 ubiquitin chains, whereas the RNF168 RING domain is a monomer and does not catalyze Lys-6 ubiquitylation. PMID: 22589545
25. Data show that depletion of RNF8, as well as of the E3 ligase RNF168, reduces telomere-induced genome instability. PMID: 21857671
26. Studies indicate that Non-proteolytic ubiquitylation of chromatin surrounding DSBs, mediated by the RNF8/RNF168 ubiquitin ligase cascade, has emerged as a key mechanism for restoration of genome integrity. PMID: 21664912
27. The viral protein ICP0 targets RNF8 and RNF168 for degradation, thereby preventing the deposition of repressive ubiquitin marks and counteracting this repair protein recruitment. PMID: 21698222
28. this study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1gamma. PMID: 21784059
29. The E3 Ubiquitin ligases, RNF8 and RNF168, are recruited to DNA damage foci in late mitosis, presumably to prime sites for the DNA damage response, 53BP1, recruitment in early G1. PMID: 21412056
30. identification of a novel ubiquitin binding domain present in RNF168, and characterized the interaction surface with ubiquitin, centered on two Leu residues PMID: 21041483
31. Data identify RNF8 and RNF168, cellular histone ubiquitin ligases responsible for anchoring repair factors at sites of damage, as new targets for ICP0-mediated degradation. PMID: 20075863
32. Ubiquitin ligase does not protect cells from Nutlin-3-mediated apoptosis, indicating that RNF168 does not regulate 53BP1 protein. PMID: 20080757
33. Data show that the ATM signalling mediator proteins MDC1, RNF8, RNF168 and 53BP1 are also required for heterochromatic DSB repair. PMID: 20081839
34. RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance. PMID: 19203579
35. RNF168 is a ubiquitin ligase that functions as chromatin modifier, through histone ubiquitination; upon DNA lesions, RNF168 is recruited to DNA damage response foci where it contributes to increase the amount of ubiquitinated proteins. PMID: 19500350
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相關疾病：

Riddle syndrome (RIDDLES)
亞細胞定位：

Nucleus.
蛋白家族：

RNF168 family
數據庫鏈接：

HGNC: 26661

OMIM: 611943

KEGG: hsa:165918

STRING: 9606.ENSP00000320898

UniGene: Hs.250648