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Ube2w-KO 基因敲除小鼠
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基本信息
基因研究概述
质控标准
基因
基因全称
ubiquitin-conjugating enzyme E2W (putative)
基因别称
6130401J04Rik
染色体号
Chr 1 (Mouse)
NCBI ID
转录本 ID
NCBI: NM_025773 | Ensembl: ENSMUST00000117146
修饰方式
全身性基因敲除
靶向范围
Exon 2~5
敲除长度
~21.7 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成，建议您在购买前查询最新的数据库和相关文献，以获取最准确的表型信息。
表型提示
MGI:1914049Mice homozygous for a knock-out allele exhibit partial prenatal, neonatal and early postnatal lethality, reduced male fertility and skin defects.
基因UBE2W，也称为Ubiquitin-conjugating enzyme E2W，是一种重要的蛋白质编码基因。它在泛素化过程中发挥着重要作用，而泛素化是一种调节蛋白质功能的机制，涉及将泛素分子共价连接到靶蛋白上。UBE2W在DNA损伤修复中可能具有关键作用[1]。此外，UBE2W还在蛋白质的N-末端进行非典型的泛素化，这可能影响蛋白质的稳定性和功能[6]。
UBE2W在多种癌症中表现出异常表达，并可能与肿瘤的免疫抑制和转移有关。例如，在乳腺癌中，UBE2W的高表达与DNA修复相关基因突变水平、DNA甲基转移酶和BRCA1/2表达显著相关[1]。此外，UBE2W的高表达可能促进乳腺癌细胞的免疫抑制和转移，并导致内分泌治疗耐药性增加，从而恶化患者的预后[1]。
UBE2W还与多种神经退行性疾病相关，包括亨廷顿病和帕金森病。研究发现，UBE2W的缺乏可以减少亨廷顿病相关蛋白htt的聚集，并增加可溶性单体的水平，从而降低htt诱导的细胞毒性[5]。此外，UBE2W还与α-突触核蛋白的水平相关，α-突触核蛋白是帕金森病和相关神经退行性疾病的重要致病因素[2]。
UBE2W的功能与其与其他蛋白质的相互作用密切相关。例如，UBE2W可以与Cbl蛋白相互作用，Cbl蛋白是一种E3泛素连接酶，参与受体酪氨酸激酶的负调控[4]。此外，UBE2W还可以与RNF4相互作用，RNF4是一种SUMO靶向泛素连接酶，参与DNA损伤反应[3]。
UBE2W在多种疾病中发挥重要作用，包括癌症、神经退行性疾病和DNA损伤修复。UBE2W的异常表达和功能改变可能与疾病的发病机制和预后相关。因此，UBE2W可能成为潜在的生物标志物和治疗靶点，为相关疾病的研究和临床应用提供新的思路和策略。
参考文献：
1. Yuan, Yan, Xiao, Wei-Wei, Xie, Wei-Hao, Li, Rong-Zhen, Gao, Yuan-Hong. 2021. Prognostic value of ubiquitin E2 UBE2W and its correlation with tumor-infiltrating immune cells in breast cancer. In BMC cancer, 21, 479. doi:10.1186/s12885-021-08234-4.
2. Santhosh Kumar, Saranya, Naseri, Nima N, Pather, Sarshan R, Rhoades, Elizabeth, Shalem, Ophir. 2024. Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. In Science advances, 10, eadj4767. doi:10.1126/sciadv.adj4767.
3. Maure, Jean-François, Moser, Sandra C, Jaffray, Ellis G, F Alpi, Arno, Hay, Ronald T. 2016. Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage. In Scientific reports, 6, 26178. doi:10.1038/srep26178.
4. Davies, Christopher W, Vidal, Simon E, Phu, Lilian, Kirkpatrick, Donald S, Koerber, James T. 2021. Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W. In Nature communications, 12, 4608. doi:10.1038/s41467-021-24669-6.
5. Liyasova, Mariya S, Ma, Ke, Voeller, Donna, Klevit, Rachel E, Lipkowitz, Stanley. 2019. Cbl interacts with multiple E2s in vitro and in cells. In PloS one, 14, e0216967. doi:10.1371/journal.pone.0216967.
6. Wang, Bo, Merillat, Sean A, Vincent, Michael, Scaglione, Kenneth Matthew, Paulson, Henry L. 2015. Loss of the Ubiquitin-conjugating Enzyme UBE2W Results in Susceptibility to Early Postnatal Lethality and Defects in Skin, Immune, and Male Reproductive Systems. In The Journal of biological chemistry, 291, 3030-42. doi:10.1074/jbc.M115.676601.
7. Wang, Bo, Zeng, Li, Merillat, Sean A, Scaglione, Kenneth M, Paulson, Henry L. 2017. The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin. In Neurobiology of disease, 109, 127-136. doi:10.1016/j.nbd.2017.10.002.
8. Anyona, Samuel B, Cheng, Qiuying, Raballah, Evans, Ouma, Collins, Perkins, Douglas J. 2022. Ingestion of hemozoin by peripheral blood mononuclear cells alters temporal gene expression of ubiquitination processes. In Biochemistry and biophysics reports, 29, 101207. doi:10.1016/j.bbrep.2022.101207.
9. Tatham, Michael H, Plechanovová, Anna, Jaffray, Ellis G, Salmen, Helena, Hay, Ronald T. . Ube2W conjugates ubiquitin to α-amino groups of protein N-termini. In The Biochemical journal, 453, 137-45. doi:10.1042/BJ20130244.
10. Chauhan, Abhishek Singh, Tiwari, Madhu, Indoliya, Yuvraj, Chakrabarty, Debasis, Tripathi, Rudra Deo. 2023. Identification and validation of reference genes in vetiver (Chrysopogon zizanioides) root transcriptome. In Physiology and molecular biology of plants : an international journal of functional plant biology, 29, 613-627. doi:10.1007/s12298-023-01315-7.
参考文献：
1. Yuan, Yan, Xiao, Wei-Wei, Xie, Wei-Hao, Li, Rong-Zhen, Gao, Yuan-Hong. 2021. Prognostic value of ubiquitin E2 UBE2W and its correlation with tumor-infiltrating immune cells in breast cancer. In BMC cancer, 21, 479. doi:10.1186/s12885-021-08234-4. https://pubmed.ncbi.nlm.nih.gov/33931024/
2. Santhosh Kumar, Saranya, Naseri, Nima N, Pather, Sarshan R, Rhoades, Elizabeth, Shalem, Ophir. 2024. Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons. In Science advances, 10, eadj4767. doi:10.1126/sciadv.adj4767. https://pubmed.ncbi.nlm.nih.gov/38335281/
3. Maure, Jean-François, Moser, Sandra C, Jaffray, Ellis G, F Alpi, Arno, Hay, Ronald T. 2016. Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage. In Scientific reports, 6, 26178. doi:10.1038/srep26178. https://pubmed.ncbi.nlm.nih.gov/27185577/
4. Liyasova, Mariya S, Ma, Ke, Voeller, Donna, Klevit, Rachel E, Lipkowitz, Stanley. 2019. Cbl interacts with multiple E2s in vitro and in cells. In PloS one, 14, e0216967. doi:10.1371/journal.pone.0216967. https://pubmed.ncbi.nlm.nih.gov/31120930/
5. Wang, Bo, Zeng, Li, Merillat, Sean A, Scaglione, Kenneth M, Paulson, Henry L. 2017. The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin. In Neurobiology of disease, 109, 127-136. doi:10.1016/j.nbd.2017.10.002. https://pubmed.ncbi.nlm.nih.gov/28986324/
6. Tatham, Michael H, Plechanovová, Anna, Jaffray, Ellis G, Salmen, Helena, Hay, Ronald T. . Ube2W conjugates ubiquitin to α-amino groups of protein N-termini. In The Biochemical journal, 453, 137-45. doi:10.1042/BJ20130244. https://pubmed.ncbi.nlm.nih.gov/23560854/
| 精子检测 | ① 冷冻前验证精子活力观察 ② 冷冻验证每批次进行复苏验证 | 交付状态 | 活体/精子 |
| 环境标准 | SPF | 供应地区 | 中国 |
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