UHRF1

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.[5][6]

UHRF1
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, 5C6D, 5IAY
Identifiers
Aliases	UHRF1, ICBP90, Np95, RNF106, hNP95, hhuNp95, TDRD22, ubiquitin like with PHD and ring finger domains 1
External IDs	OMIM: 607990 MGI: 1338889 HomoloGene: 7866 GeneCards: UHRF1
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 4,903,080 bp[1] End 4,962,154 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 D Start 56,303,321 bp[2] End 56,323,486 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity • hemi-methylated DNA-binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • methyl-CpG binding • GO:0001158 core promoter proximal region sequence-specific DNA binding • metal ion binding • ubiquitin-protein transferase activity • nucleosomal histone binding • methylated histone binding • GO:0001948 protein binding • identical protein binding • transferase activity • zinc ion binding • histone binding Cellular component • euchromatin • nuclear matrix • replication fork • heterochromatin • nuclear heterochromatin • nuclear chromatin • cell nucleus Biological process • histone monoubiquitination • positive regulation of cellular protein metabolic process • regulation of transcription, DNA-templated • maintenance of DNA methylation • positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • regulation of methylation-dependent chromatin silencing • cellular response to DNA damage stimulus • protein ubiquitination • cell cycle • cellular proliferation • histone ubiquitination • DNA repair • positive regulation of transcription from RNA polymerase II promoter • protein autoubiquitination • chromatin organization • ubiquitin-dependent protein catabolic process • regulation of epithelial cell proliferation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	29128	18140
Ensembl	ENSG00000276043	ENSMUSG00000001228
UniProt	Q96T88	Q8VDF2
RefSeq (mRNA)	NM_001048201 NM_001290050 NM_001290051 NM_001290052 NM_013282	NM_001111078 NM_001111079 NM_001111080 NM_010931
RefSeq (protein)	NP_001041666 NP_001276979 NP_001276980 NP_001276981 NP_037414	NP_001104548 NP_001104549 NP_001104550 NP_035061
Location (UCSC)	Chr 19: 4.9 – 4.96 Mb	Chr 17: 56.3 – 56.32 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to hemi-methylated DNA during S-phase and recruits the main DNA methyltransferase protein, 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, and functions in the p53-dependent DNA damage checkpoint. Multiple transcript variants encoding different isoforms have been found for this gene. It was originally identified as a direct regulator of topoisomerase 2a, but this has subsequently been disproven. Uhrf1 has been extensively studied in vivo using zebrafish.

Clinical significance

UHRF1 has recently been identified as a novel oncogene in hepatocellular carcinoma, the primary type of liver cancer.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000276043 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001228 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: UHRF1 ubiquitin-like, containing PHD and RING finger domains, 1".
6. 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.
7. Mudbhary, Raksha; Hoshida, Yujin; Chernyavskaya, Yelena; Jacob, Vinitha; Villanueva, Augusto; Fiel, M. Isabel; Chen, Xintong; Kojima, Kensuke; Thung, Swan; Bronson, Roderick T.; Lachenmayer, Anja; Revill, Kate; Alsinet, Clara; Sachidanandam, Ravi; Desai, Anal; Senbanerjee, Sucharita; Ukomadu, Chinweike; Llovet, Josep M.; Sadler, Kirsten C. (2014). "UHRF1 Overexpression Drives DNA Hypomethylation and Hepatocellular Carcinoma". Cancer Cell. 25 (2): 196–209. doi:10.1016/j.ccr.2014.01.003. PMC 3951208. PMID 24486181.

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. 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. 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.