Gene Symbol: ORC5
Description: origin recognition complex subunit 5
Alias: ORC5L, ORC5P, ORC5T, PPP1R117, origin recognition complex subunit 5, protein phosphatase 1, regulatory subunit 117
Species: human
Products:     ORC5

Top Publications

  1. Bell S, Dutta A. DNA replication in eukaryotic cells. Annu Rev Biochem. 2002;71:333-74 pubmed
    ..We emphasize recent progress in determining the function of the different replication factors once they have been assembled at the origin. ..
  2. Mimura S, Yamaguchi T, Ishii S, Noro E, Katsura T, Obuse C, et al. Cul8/Rtt101 forms a variety of protein complexes that regulate DNA damage response and transcriptional silencing. J Biol Chem. 2010;285:9858-67 pubmed publisher
    ..We also found other Cul8-Mms1-binding proteins Ctf4, Esc2, and Orc5 using yeast two-hybrid screening...
  3. Neves Costa A, Will W, Vetter A, Miller J, Varga Weisz P. The SNF2-family member Fun30 promotes gene silencing in heterochromatic loci. PLoS ONE. 2009;4:e8111 pubmed publisher
    ..to sensitivity to the topoisomerase I poison camptothecin and to severe cell cycle progression defects when the Orc5 subunit is mutated...
  4. Li N, Lam W, Zhai Y, Cheng J, Cheng E, Zhao Y, et al. Structure of the origin recognition complex bound to DNA replication origin. Nature. 2018;559:217-222 pubmed publisher
    ..insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA...
  5. Kim S, Ho J, Jin H, Lee S, Lee S, Hong S, et al. Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines. Investig Clin Urol. 2016;57:63-72 pubmed publisher
    ..These genes were PRKAR2A, PRKAR2B, CYCS, BCL2, BIRC3, DFFB, CASP6, CDK6, CCNE1, STEAP3, MCM7, ORC2, ORC5, ANAPC1, and ANAPC7, CDC7, CDC27, and SKP1...
  6. Stark M, Tom L, Boyle G, Bonazzi V, Soyer H, Herington A, et al. The "melanoma-enriched" microRNA miR-4731-5p acts as a tumour suppressor. Oncotarget. 2016;7:49677-49687 pubmed publisher
    ..These data revealed that miR-4731 regulates multiple genes associated with the cell cycle (e.g. CCNA2, ORC5L, and PCNA) and the melanosome (e.g. RAB7A, CTSD, and GNA13)...
  7. Syed S, Desler C, Rasmussen L, Schmidt K. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression. PLoS Genet. 2016;12:e1006451 pubmed publisher
    ..N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex...
  8. Keller C, Ladenburger E, Kremer M, Knippers R. The origin recognition complex marks a replication origin in the human TOP1 gene promoter. J Biol Chem. 2002;277:31430-40 pubmed
    ..Nascent strand abundance assays gave no indication that the heterochromatin sequence serves as a replication initiation site, suggesting that an ORC on this site may perform functions other than replication initiation. ..
  9. Ishiai M, Dean F, Okumura K, Abe M, Moon K, Amin A, et al. Isolation of human and fission yeast homologues of the budding yeast origin recognition complex subunit ORC5: human homologue (ORC5L) maps to 7q22. Genomics. 1997;46:294-8 pubmed
    ..pombe, and S. cerevisiae Orc5p, respectively. We have localized the human ORC5 gene (ORC5L) to chromosome 7 using Southern and PCR analysis of DNA isolated from a panel of human/rodent somatic cell hybrids ..

More Information


  1. Volkening M, Hoffmann I. Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin. Mol Cell Biol. 2005;25:1560-8 pubmed
    ..These results suggest that hMCM8 is a crucial component of the pre-RC and that the interaction between hMCM8 and hcdc6 is required for pre-RC assembly. ..
  2. Klemm R, Austin R, Bell S. Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell. 1997;88:493-502 pubmed
    ..cerevisiae. Origin recognition by ORC requires ATP. Here, we demonstrate that two subunits, Orc1p and Orc5p, bind ATP and that Orc1p also hydrolyzes ATP...
  3. Tugal T, Zou Yang X, Gavin K, Pappin D, Canas B, Kobayashi R, et al. The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p. J Biol Chem. 1998;273:32421-9 pubmed
    ..of the 43- and 48-kDa proteins that copurified with Orc1p and Orc2p led to their identification as the Orc4p and Orc5p subunits, respectively...
  4. Sar F, Lindsey Boltz L, Subramanian D, Croteau D, Hutsell S, Griffith J, et al. Human claspin is a ring-shaped DNA-binding protein with high affinity to branched DNA structures. J Biol Chem. 2004;279:39289-95 pubmed
  5. Clarke C, Clarke P. DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system. Biochem J. 2005;388:705-12 pubmed
    ..This cell-free system will facilitate further biochemical analysis of the Chk1 pathway in humans. ..
  6. Kuo A, Song J, Cheung P, Ishibe Murakami S, Yamazoe S, Chen J, et al. The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature. 2012;484:115-9 pubmed publisher
  7. Ranjan A, Gossen M. A structural role for ATP in the formation and stability of the human origin recognition complex. Proc Natl Acad Sci U S A. 2006;103:4864-9 pubmed
    ..ATP is essential for the maintenance of ORC integrity and facilitates complex formation. Thus, besides its previously identified role in DNA binding, ATP serves also as a structural cofactor for human ORC. ..
  8. Jiang W, McDonald D, Hope T, Hunter T. Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication. EMBO J. 1999;18:5703-13 pubmed
    ..These results indicate that the HsCdc7-HsDbf4 kinase is directly involved in regulating the initiation of DNA replication by targeting MCM2 protein in mammalian cells. ..
  9. Giri S, Chakraborty A, Sathyan K, Prasanth K, Prasanth S. Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner. J Cell Sci. 2016;129:417-29 pubmed publisher
    ..We demonstrate that human Orc5, unlike other ORC subunits, when ectopically tethered to a chromatin locus, induces large-scale chromatin ..
  10. Shen Z, Sathyan K, Geng Y, Zheng R, Chakraborty A, Freeman B, et al. A WD-repeat protein stabilizes ORC binding to chromatin. Mol Cell. 2010;40:99-111 pubmed publisher
    ..Our results suggest ORCA-mediated association of ORC to chromatin is critical to initiate preRC assembly in G1 and chromatin organization in post-G1 cells. ..
  11. Dhar S, Delmolino L, Dutta A. Architecture of the human origin recognition complex. J Biol Chem. 2001;276:29067-71 pubmed
    ..The C-terminal region of ORC3 was, however, necessary to bring ORC4 and ORC5 into the core complex...
  12. Kopytova D, Popova V, Kurshakova M, Shidlovskii Y, Nabirochkina E, Brechalov A, et al. ORC interacts with THSC/TREX-2 and its subunits promote Nxf1 association with mRNP and mRNA export in Drosophila. Nucleic Acids Res. 2016;44:4920-33 pubmed publisher
    ..ORC subunits interacted with the Nxf1 receptor mediating the bulk mRNA export. The knockdown of Orc5 led to a drop in the Nxf1 association with mRNP, while Orc3 knockdown increased the level of mRNP-bound Nxf1...
  13. Maurer S, Ludt K, Soppa J. Characterization of Copy Number Control of Two Haloferax volcanii Replication Origins Using Deletion Mutants and Haloarchaeal Artificial Chromosomes. J Bacteriol. 2018;200: pubmed publisher
    ..had a lower genome copy number and a higher level of fitness than the wild type, in stark contrast to the oriC2-orc5 (ori2) deletion mutant...
  14. Pinto S, Quintana D, Smith P, Mihalek R, Hou Z, Boynton S, et al. latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Neuron. 1999;23:45-54 pubmed
    ..Human and Drosophila LAT both associate with ORC2 and are related to yeast ORC3, suggesting that LAT functions in DNA replication during cell proliferation. ..
  15. Quintana D, Thome K, Hou Z, Ligon A, Morton C, Dutta A. ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases. J Biol Chem. 1998;273:27137-45 pubmed
    ..HsORC5p is a 50-kDa protein whose sequence is 38% identical and 62% similar to ORC5p from Drosophila melanogaster...
  16. Siddiqui K, Stillman B. ATP-dependent assembly of the human origin recognition complex. J Biol Chem. 2007;282:32370-83 pubmed
    ..Mutations in the ATP-binding sites of Orc4 or Orc5 impair complex assembly, whereas Orc1 ATP binding is not required...
  17. Thome K, Dhar S, Quintana D, Delmolino L, Shahsafaei A, Dutta A. Subsets of human origin recognition complex (ORC) subunits are expressed in non-proliferating cells and associate with non-ORC proteins. J Biol Chem. 2000;275:35233-41 pubmed
    ..Orc2, Orc3, and Orc5 also are detected in non-proliferating cells like cardiac myocytes, adrenal cortical cells, and neurons, suggesting ..
  18. Vashee S, Simancek P, Challberg M, Kelly T. Assembly of the human origin recognition complex. J Biol Chem. 2001;276:26666-73 pubmed
    ..The endogenous HsORC, identified in these experiments, contained homologues of Orc1-Orc5 but lacked a putative homologue of Orc6...
  19. Wohlschlegel J, Dwyer B, Dhar S, Cvetic C, Walter J, Dutta A. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science. 2000;290:2309-12 pubmed
    ..In the normal cell cycle, Cdt1 is present only in G1 and S, whereas geminin is present in S and G2 phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1. ..
  20. Herbig U, Marlar C, Fanning E. The Cdc6 nucleotide-binding site regulates its activity in DNA replication in human cells. Mol Biol Cell. 1999;10:2631-45 pubmed
    ..Microinjection of either mutant protein into human cells in G1 inhibited DNA replication, suggesting that ATP binding and hydrolysis by HsCdc6 are essential for DNA replication. ..
  21. Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon K, et al. The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Nucleic Acids Res. 2000;28:4769-77 pubmed
    ..HsMcm10 also interacted with Orc2, Mcm2 and Mcm6 proteins in the yeast two-hybrid system. These results suggest that HsMcm10 may function in DNA replication through the interaction with Orc and Mcm2-7 complexes. ..
  22. Fröhling S, Nakabayashi K, Scherer S, Dohner H, Dohner K. Mutation analysis of the origin recognition complex subunit 5 (ORC5L) gene in adult patients with myeloid leukemias exhibiting deletions of chromosome band 7q22. Hum Genet. 2001;108:304-9 pubmed
    The ORC5L gene encoding a subunit of the human origin recognition complex (ORC) maps to chromosome band 7q22, a region frequently deleted in adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)...