Gene Symbol: Np95
Description: ubiquitin-like, containing PHD and RING finger domains, 1
Alias: AL022808, ICBP90, Np95, RNF106, E3 ubiquitin-protein ligase UHRF1, RING-type E3 ubiquitin transferase UHRF1, mUhrf1, nuclear protein 95, nuclear zinc finger protein Np95, ubiquitin-like PHD and RING finger domain-containing protein 1, ubiquitin-like-containing PHD and RING finger domains protein 1
Species: mouse
Products:     Np95

Top Publications

  1. Uemura T, Kubo E, Kanari Y, Ikemura T, Tatsumi K, Muto M. Temporal and spatial localization of novel nuclear protein NP95 in mitotic and meiotic cells. Cell Struct Funct. 2000;25:149-59 pubmed
    Expression of novel NP95 (nuclear protein, 95 kDa), which contains a leucine zipper motif, a zinc finger motif, a putative cyclin A/E-cyclin-dependent protein kinase 2 phosphorylation site, and retinoblastoma protein-binding motifs, is ..
  2. Miura M, Watanabe H, Sasaki T, Tatsumi K, Muto M. Dynamic changes in subnuclear NP95 location during the cell cycle and its spatial relationship with DNA replication foci. Exp Cell Res. 2001;263:202-8 pubmed
    We determined the expression and subcellular localization of nuclear protein NP95 during the cell cycle in mouse 3T3 cells...
  3. Papait R, Pistore C, Grazini U, Babbio F, Cogliati S, Pecoraro D, et al. The PHD domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin. Mol Biol Cell. 2008;19:3554-63 pubmed publisher
    ..Np95-ICBP90 (m- and h-UHRF1) is a histone-binding protein expressed only in proliferating cells...
  4. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo T, et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007;450:908-12 pubmed
    ..The Np95 (also known as Uhrf1 and ICBP90) protein binds methylated CpG through its SET and RING finger-associated (SRA) domain...
  5. Bostick M, Kim J, Esteve P, Clark A, Pradhan S, Jacobsen S. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317:1760-4 pubmed
    ..that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation...
  6. Kim J, Esteve P, Jacobsen S, Pradhan S. UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells. Nucleic Acids Res. 2009;37:493-505 pubmed publisher
    ..Thus, our results suggest that UHRF1 may serve as a focal point of transcriptional regulation mediated by G9a and other chromatin modification enzymes. ..
  7. Bonapace I, Latella L, Papait R, Nicassio F, Sacco A, Muto M, et al. Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. J Cell Biol. 2002;157:909-14 pubmed
    ..In this study, we identified the gene encoding Np95, a murine nuclear phosphoprotein, as an early target of E1A-induced transcriptional events...
  8. Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature. 2008;455:818-21 pubmed publisher
    ..The protein UHRF1 (also known as Np95 and ICBP90) recognizes hemi-methylation sites via a SET and RING-associated (SRA) domain and directs Dnmt1 to these sites...
  9. Hashimoto H, Horton J, Zhang X, Bostick M, Jacobsen S, Cheng X. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature. 2008;455:826-9 pubmed publisher
    ..Hence, UHRF1 contains a previously unknown DNA-binding module and is the first example of a non-enzymatic, sequence-specific DNA-binding protein domain to use the base flipping mechanism to interact with DNA. ..

More Information


  1. Citterio E, Papait R, Nicassio F, Vecchi M, Gomiero P, Mantovani R, et al. Np95 is a histone-binding protein endowed with ubiquitin ligase activity. Mol Cell Biol. 2004;24:2526-35 pubmed
    b>Np95 is an important determinant in cell cycle progression. Its expression is tightly regulated and becomes detectable shortly before the entry of cells into S phase. Accordingly, Np95 is absolutely required for the G1/S transition...
  2. Papait R, Pistore C, Negri D, Pecoraro D, Cantarini L, Bonapace I. Np95 is implicated in pericentromeric heterochromatin replication and in major satellite silencing. Mol Biol Cell. 2007;18:1098-106 pubmed
    ..b>Np95 is a cell cycle regulated and is a nuclear histone-binding protein that also recruits HDAC-1 to target promoters...
  3. Fujimori A, Matsuda Y, Takemoto Y, Hashimoto Y, Kubo E, Araki R, et al. Cloning and mapping of Np95 gene which encodes a novel nuclear protein associated with cell proliferation. Mamm Genome. 1998;9:1032-5 pubmed
    We previously obtained a monoclonal antibody (Th-10a mAb) that recognizes a single 95-kDa mouse nuclear protein (NP95). Immunostaining analyses revealed that the NP95 was specifically stained in the S phase of normal mouse thymocytes...
  4. Unoki M, Nishidate T, Nakamura Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004;23:7601-10 pubmed
    b>ICBP90, inverted CCAAT box-binding protein of 90 kDa, has been reported as a regulator of topoisomerase IIalpha expression...
  5. Muto M, Utsuyama M, Horiguchi T, Kubo E, Sado T, Hirokawa K. The characterization of the monoclonal antibody Th-10a, specific for a nuclear protein appearing in the S phase of the cell cycle in normal thymocytes and its unregulated expression in lymphoma cell lines. Cell Prolif. 1995;28:645-57 pubmed
    ..The nuclear protein(s) detected by Th-10a monoclonal antibody was mostly 95 kDa and also 83 kDa polypeptide. The results also indicated that the 95 kDa nuclear protein was phosphorylated in vivo. ..
  6. Zhao J, Chen X, Song G, Zhang J, Liu H, Liu X. Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes. Proc Natl Acad Sci U S A. 2017;114:E142-E151 pubmed publisher
  7. Fang J, Cheng J, Wang J, Zhang Q, Liu M, Gong R, et al. Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition. Nat Commun. 2016;7:11197 pubmed publisher
    ..When TTD-PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin. Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1. ..
  8. Meng H, Harrison D, Meehan R. MBD4 interacts with and recruits USP7 to heterochromatic foci. J Cell Biochem. 2015;116:476-85 pubmed publisher
    ..The ability of MBD4 to directly interact with and recruit USP7 to chromocenters implicates it as an additional factor that can potentially regulate Dnmt1 activity during cell proliferation. ..
  9. Maenohara S, Unoki M, Toh H, Ohishi H, Sharif J, Koseki H, et al. Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. PLoS Genet. 2017;13:e1007042 pubmed publisher
    ..Our study reveals multiple functions of UHRF1 during the global epigenetic reprogramming of oocytes and early embryos...
  10. Hashimoto H, Horton J, Zhang X, Cheng X. UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications. Epigenetics. 2009;4:8-14 pubmed
    ..We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication. ..
  11. Ding G, Chen P, Zhang H, Huang X, Zang Y, Li J, et al. Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery. J Biol Chem. 2016;291:20125-35 pubmed publisher
    ..Taken together, our results identify UHRF1 as a novel HSP90 client protein and shed light on the regulation of UHRF1 stability and function. ..
  12. Hervouet E, Lalier L, Debien E, Cheray M, Geairon A, Rogniaux H, et al. Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS ONE. 2010;5:e11333 pubmed publisher
    ..We identify the genetic and epigenetic alterations which collectively promote the acquisition of tumor/glioma traits by human astrocytes and glial progenitor cells as that promoting high proliferation and apoptosis evasion. ..
  13. Sharif J, Endo T, Nakayama M, Karimi M, Shimada M, Katsuyama K, et al. Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA. Cell Stem Cell. 2016;19:81-94 pubmed publisher
    ..Conditional deletions reveal that both Dnmt1 and Np95 are essential for maintenance DNA methylation...
  14. Obata Y, Furusawa Y, Endo T, Sharif J, Takahashi D, Atarashi K, et al. The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. Nat Immunol. 2014;15:571-9 pubmed publisher
    ..Thus, Uhrf1-dependent epigenetic silencing of Cdkn1a was required for the maintenance of gut immunological homeostasis. This mechanism enforces symbiotic host-microbe interactions without an inflammatory response. ..
  15. Oda M, Oxley D, Dean W, Reik W. Regulation of lineage specific DNA hypomethylation in mouse trophectoderm. PLoS ONE. 2013;8:e68846 pubmed publisher
    ..Interestingly, Dnmt1 localization was restored by exogenous Np95/Uhrf1, a Dnmt1 chaperone required for Dnmt1-targeting to replication foci, yet DNA methylation levels remained low...
  16. Karg E, Smets M, Ryan J, Forne I, Qin W, Mulholland C, et al. Ubiquitome Analysis Reveals PCNA-Associated Factor 15 (PAF15) as a Specific Ubiquitination Target of UHRF1 in Embryonic Stem Cells. J Mol Biol. 2017;: pubmed publisher
    ..In summary, we identified novel ubiquitination targets that link UHRF1 to transcriptional regulation and DNA damage response...
  17. Yamashita M, Inoue K, Saeki N, Ideta Otsuka M, Yanagihara Y, Sawada Y, et al. Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression. Development. 2018;145: pubmed publisher
  18. Nady N, Lemak A, Walker J, Avvakumov G, Kareta M, Achour M, et al. Recognition of multivalent histone states associated with heterochromatin by UHRF1 protein. J Biol Chem. 2011;286:24300-11 pubmed publisher
  19. Mistry H, Gibson L, Yun J, Sarras H, Tamblyn L, McPherson J. Interplay between Np95 and Eme1 in the DNA damage response. Biochem Biophys Res Commun. 2008;375:321-5 pubmed publisher
    ..Here, we report mammalian Eme1 interacts with Np95, an E3 ubiquitin ligase that participates in chromatin modification, replication-linked epigenetic maintenance and ..
  20. Berkyurek A, Suetake I, Arita K, Takeshita K, Nakagawa A, Shirakawa M, et al. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA. J Biol Chem. 2014;289:379-86 pubmed publisher
    ..The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center. ..
  21. Liu X, Gao Q, Li P, Zhao Q, Zhang J, Li J, et al. UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9. Nat Commun. 2013;4:1563 pubmed publisher
    ..In addition, our study indicates that UHRF1 mediates cross-talk between H3K9 methylation and DNA methylation at the level of DNA methylation maintenance. ..
  22. Qi S, Wang Z, Li P, Wu Q, Shi T, Li J, et al. Non-germ Line Restoration of Genomic Imprinting for a Small Subset of Imprinted Genes in Ubiquitin-like PHD and RING Finger Domain-Containing 1 (Uhrf1) Null Mouse Embryonic Stem Cells. J Biol Chem. 2015;290:14181-91 pubmed publisher
  23. Lu L, Kuang H, Korakavi G, Yu X. Topoisomerase II regulates the maintenance of DNA methylation. J Biol Chem. 2015;290:851-60 pubmed publisher
    ..Inhibiting this activity impairs DNA methylation at multiple genomic loci. We have uncovered a novel mechanism during the maintenance of DNA methylation. ..
  24. Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, et al. Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature. 2013;502:249-53 pubmed publisher is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an ..
  25. Shamma A, Suzuki M, Hayashi N, Kobayashi M, Sasaki N, Nishiuchi T, et al. ATM mediates pRB function to control DNMT1 protein stability and DNA methylation. Mol Cell Biol. 2013;33:3113-24 pubmed publisher
    ..Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. ..
  26. Bracht T, Hagemann S, Loscha M, Megger D, Padden J, Eisenacher M, et al. Proteome analysis of a hepatocyte-specific BIRC5 (survivin)-knockout mouse model during liver regeneration. J Proteome Res. 2014;13:2771-82 pubmed publisher
    ..Our results show that the E3 ubiquitin-protein ligase UHRF1 is strongly up-regulated during liver regeneration independently of BIRC5. ..
  27. Bashtrykov P, Jankevicius G, Jurkowska R, Ragozin S, Jeltsch A. The UHRF1 protein stimulates the activity and specificity of the maintenance DNA methyltransferase DNMT1 by an allosteric mechanism. J Biol Chem. 2014;289:4106-15 pubmed publisher
    ..These findings show that apart from the targeting of DNMT1 to the replicated DNA UHRF1 increases the activity and specificity of DNMT1, thus exerting a multifaceted influence on the maintenance of DNA methylation. ..
  28. Graf U, Casanova E, Wyck S, Dalcher D, Gatti M, Vollenweider E, et al. Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways. Nat Cell Biol. 2017;19:763-773 pubmed publisher
    ..Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency. ..
  29. Smets M, Link S, Wolf P, Schneider K, Solis V, Ryan J, et al. DNMT1 mutations found in HSANIE patients affect interaction with UHRF1 and neuronal differentiation. Hum Mol Genet. 2017;26:1522-1534 pubmed publisher
    ..Our results provide insights into the molecular basis of DNMT1 dysfunction in HSANIE patients and emphasize the importance of the TS domain in the regulation of DNA methylation in pluripotent and differentiating cells. ..
  30. De Vos M, El Ramy R, Quenet D, Wolf P, Spada F, Magroun N, et al. Poly(ADP-ribose) polymerase 1 (PARP1) associates with E3 ubiquitin-protein ligase UHRF1 and modulates UHRF1 biological functions. J Biol Chem. 2014;289:16223-38 pubmed publisher
    ..functional poly(ADP-ribose)-mediated interaction of PARP1 with the E3 ubiquitin ligase UHRF1 (also known as NP95, ICBP90) that influences two UHRF1-regulated cellular processes...
  31. Muto M, Kanari Y, Kubo E, Takabe T, Kurihara T, Fujimori A, et al. Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks. J Biol Chem. 2002;277:34549-55 pubmed
    b>NP95, which contains a ubiquitin-like domain, a cyclin A/E-Cdk2 phosphorylation site, a retinoblastoma (Rb) binding motif, and a ring finger domain, has been shown to be colocalized as foci with proliferating cell nuclear antigen in early ..
  32. Mori T, Li Y, Hata H, Kochi H. NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein. FEBS Lett. 2004;557:209-14 pubmed
    We previously reported the association of a novel Np95/ICBP90-like RING finger protein (NIRF) with a novel PEST-containing nuclear protein (PCNP)...
  33. Ramesh V, Bayam E, Cernilogar F, Bonapace I, Schulze M, Riemenschneider M, et al. Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration. Genes Dev. 2016;30:2199-2212 pubmed
    ..of neural stem cells (NSCs) and their progeny, we examined Uhrf1 (ubiquitin-like PHD ring finger-1; also known as Np95), as it is highly expressed in NSCs of the developing brain and rapidly down-regulated upon differentiation...
  34. Qin W, Leonhardt H, Spada F. Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1. J Cell Biochem. 2011;112:439-44 pubmed publisher
    ..Overexpression of Uhrf1 and Usp7 resulted in opposite changes in the ubiquitination status and stability of Dnmt1. Our findings suggest that, by balancing Dnmt1 ubiquitination, Usp7 and Uhrf1 fine tune Dnmt1 stability. ..
  35. Cui Y, Chen X, Zhang J, Sun X, Liu H, Bai L, et al. Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis. Cell Rep. 2016;15:256-63 pubmed publisher
    Uhrf1 (also known as Np95) is a regulator of DNA methylation and histone ubiquitination and plays an important role in embryogenesis and tumorigenesis...
  36. Albino D, Brizzolara A, Moretti S, Falugi C, Mirisola V, Scaruffi P, et al. Gene expression profiling identifies eleven DNA repair genes down-regulated during mouse neural crest cell migration. Int J Dev Biol. 2011;55:65-72 pubmed publisher
    ..Our model of enriched murine NCCs and neural crest-derived cells can be used to elucidate the key roles of genes during normal embryonic development and in cancer pathogenesis. ..
  37. Dugas J, Tai Y, Speed T, Ngai J, Barres B. Functional genomic analysis of oligodendrocyte differentiation. J Neurosci. 2006;26:10967-83 pubmed
  38. Daxinger L, Harten S, Oey H, Epp T, Isbel L, Huang E, et al. An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse. Genome Biol. 2013;14:R96 pubmed
    ..Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines. ..
  39. Zhang J, Gao Q, Li P, Liu X, Jia Y, Wu W, et al. S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance. Cell Res. 2011;21:1723-39 pubmed publisher
  40. Meilinger D, Fellinger K, Bultmann S, Rothbauer U, Bonapace I, Klinkert W, et al. Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells. EMBO Rep. 2009;10:1259-64 pubmed publisher
    Recent studies have indicated that nuclear protein of 95 kDa (Np95) is essential for maintaining genomic methylation by recruiting DNA methyltransferase (Dnmt) 1 to hemi-methylated sites...