UHRF1

Ubiquitin-like with PHD and ring finger domains 1
PDB rendering based on 2faz.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2FAZ​, 2L3R​, 2LGG​, 2LGK​, 2LGL​, 2PB7​, 3ASK​, 3ASL​, 3BI7​, 3CLZ​, 3DB3​, 3DB4​, 3DWH​, 3FL2​, 3SHB​, 3SOU​, 3SOW​, 3SOX​, 3T6R​, 3ZVY​, 3ZVZ​, 4GY5​, 4QQD​
Identifiers
Symbols	UHRF1 ; ICBP90; Np95; RNF106; hNP95; hUHRF1; huNp95
External IDs	OMIM: 607990 MGI: 1338889 HomoloGene: 7866 GeneCards: UHRF1 Gene
EC number	6.3.2.19
Gene ontology Molecular function • core promoter proximal region sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • ubiquitin-protein transferase activity • protein binding • zinc ion binding • methyl-CpG binding • ligase activity • nucleosomal histone binding • methylated histone binding • histone binding • identical protein binding • hemi-methylated DNA-binding • ubiquitin protein ligase activity Cellular component • nuclear chromatin • euchromatin • heterochromatin • nucleus • replication fork • nuclear matrix Biological process • negative regulation of transcription from RNA polymerase II promoter • DNA repair • transcription, DNA-templated • cell cycle • cell proliferation • maintenance of DNA methylation • histone monoubiquitination • gene expression • histone ubiquitination • positive regulation of cellular protein metabolic process • DNA methylation on cytosine • regulation of gene expression, epigenetic • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • positive regulation of transcription from RNA polymerase II promoter • protein autoubiquitination • positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	29128	18140
Ensembl	ENSG00000276043	ENSMUSG00000001228
UniProt	Q96T88	Q8VDF2
RefSeq (mRNA)	NM_001048201	NM_001111078
RefSeq (protein)	NP_001041666	NP_001104548
Location (UCSC)	Chr 19: 4.9 – 4.96 Mb	Chr 17: 56.3 – 56.32 Mb
PubMed search

Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the UHRF1 gene.^[1][2]

Function

This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA sequences, and recruits the main DNA methyltransferase gene, DNMT1, to regulate chromatin structure and gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating topoisomerase II alpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint. Multiple transcript variants encoding different isoforms have been found for this gene.^[1]

Clinical significance

UHRF1 has recently been identified as a novel oncogene in hepatocellular carcinoma, the primary type of liver cancer.^[3]

References

1. "Entrez Gene: UHRF1 ubiquitin-like, containing PHD and RING finger domains, 1".
2. Hopfner R, Mousli M, Jeltsch JM, Voulgaris A, Lutz Y, Marin C, Bellocq JP, Oudet P, Bronner C (Jan 2000). "ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression". Cancer Research 60 (1): 121–8. PMID 10646863.
3. http://www.cell.com/cancer-cell/abstract/S1535-6108%2814%2900031-2

Further reading

• Ku DH, Chang CD, Koniecki J, Cannizzaro LA, Boghosian-Sell L, Alder H, Baserga R (Apr 1991). "A new growth-regulated complementary DNA with the sequence of a putative trans-activating factor". Cell Growth & Differentiation : The Molecular Biology Journal of the American Association for Cancer Research 2 (4): 179–86. PMID 1868030.
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M (Sep 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549. Check date values in: |year= / |date= mismatch (help)
• Hopfner R, Mousli M, Jeltsch JM, Voulgaris A, Lutz Y, Marin C, Bellocq JP, Oudet P, Bronner C (Jan 2000). "ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression". Cancer Research 60 (1): 121–8. PMID 10646863.
• Hopfner R, Mousli M, Garnier JM, Redon R, du Manoir S, Chatton B, Ghyselinck N, Oudet P, Bronner C (Mar 2001). "Genomic structure and chromosomal mapping of the gene coding for ICBP90, a protein involved in the regulation of the topoisomerase IIalpha gene expression". Gene 266 (1-2): 15–23. doi:10.1016/S0378-1119(01)00371-7. PMID 11290415.
• Mousli M, Hopfner R, Abbady AQ, Monté D, Jeanblanc M, Oudet P, Louis B, Bronner C (Jul 2003). "ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells". British Journal of Cancer 89 (1): 120–7. doi:10.1038/sj.bjc.6601068. PMC 2394215. PMID 12838312.
• Citterio E, Papait R, Nicassio F, Vecchi M, Gomiero P, Mantovani R, Di Fiore PP, Bonapace IM (Mar 2004). "Np95 is a histone-binding protein endowed with ubiquitin ligase activity". Molecular and Cellular Biology 24 (6): 2526–35. doi:10.1128/MCB.24.6.2526-2535.2004. PMC 355858. PMID 14993289.
• Arima Y, Hirota T, Bronner C, Mousli M, Fujiwara T, Niwa S, Ishikawa H, Saya H (Feb 2004). "Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition". Genes to Cells : Devoted to Molecular & Cellular Mechanisms 9 (2): 131–42. doi:10.1111/j.1356-9597.2004.00710.x. PMID 15009091.
• Abbady AQ, Bronner C, Trotzier MA, Hopfner R, Bathami K, Muller CD, Jeanblanc M, Mousli M (Dec 2003). "ICBP90 expression is downregulated in apoptosis-induced Jurkat cells". Annals of the New York Academy of Sciences 1010: 300–3. doi:10.1196/annals.1299.052. PMID 15033738. Check date values in: |year= / |date= mismatch (help)
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (Jun 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. Check date values in: |year= / |date= mismatch (help)
• Trotzier MA, Bronner C, Bathami K, Mathieu E, Abbady AQ, Jeanblanc M, Muller CD, Rochette-Egly C, Mousli M (Jun 2004). "Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase IIalpha expression". Biochemical and Biophysical Research Communications 319 (2): 590–5. doi:10.1016/j.bbrc.2004.05.028. PMID 15178447.
• Unoki M, Nishidate T, Nakamura Y (Oct 2004). "ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain". Oncogene 23 (46): 7601–10. doi:10.1038/sj.onc.1208053. PMID 15361834.
• Abbady AQ, Bronner C, Bathami K, Muller CD, Jeanblanc M, Mathieu E, Klein JP, Candolfi E, Mousli M (Aug 2005). "TCR pathway involves ICBP90 gene down-regulation via E2F binding sites". Biochemical Pharmacology 70 (4): 570–9. doi:10.1016/j.bcp.2005.05.012. PMID 15964557.
• Jeanblanc M, Mousli M, Hopfner R, Bathami K, Martinet N, Abbady AQ, Siffert JC, Mathieu E, Muller CD, Bronner C (Nov 2005). "The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle". Oncogene 24 (49): 7337–45. doi:10.1038/sj.onc.1208878. PMID 16007129.
• Jenkins Y, Markovtsov V, Lang W, Sharma P, Pearsall D, Warner J, Franci C, Huang B, Huang J, Yam GC, Vistan JP, Pali E, Vialard J, Janicot M, Lorens JB, Payan DG, Hitoshi Y (Dec 2005). "Critical role of the ubiquitin ligase activity of UHRF1, a nuclear RING finger protein, in tumor cell growth". Molecular Biology of the Cell 16 (12): 5621–9. doi:10.1091/mbc.E05-03-0194. PMC 1289407. PMID 16195352. Check date values in: |year= / |date= mismatch (help)
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (Oct 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
• Muto M, Fujimori A, Nenoi M, Daino K, Matsuda Y, Kuroiwa A, Kubo E, Kanari Y, Utsuno M, Tsuji H, Ukai H, Mita K, Takahagi M, Tatsumi K (Nov 2006). "Isolation and Characterization of a Novel Human Radiosusceptibility Gene, NP95". Radiation Research 166 (5): 723–33. doi:10.1667/RR0459.1. PMID 17067204.