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1  structure 186  species 0  interactions 219  sequences 3  architectures

Family: ORC6 (PF05460)

Summary: Origin recognition complex subunit 6 (ORC6)

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This is the Wikipedia entry entitled "ORC6". More...

ORC6 Edit Wikipedia article

Origin recognition complex, subunit 6
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ORC6; ORC6L
External IDs OMIM607213 MGI1929285 HomoloGene8635 GeneCards: ORC6 Gene
RNA expression pattern
PBB GE ORC6L 219105 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 23594 56452
Ensembl ENSG00000091651 ENSMUSG00000031697
UniProt Q9Y5N6 Q3TQX1
RefSeq (mRNA) NM_014321 NM_001163791
RefSeq (protein) NP_055136 NP_001157263
Location (UCSC) Chr 16:
46.72 – 46.73 Mb
Chr 8:
85.3 – 85.31 Mb
PubMed search [1] [2]
Origin recognition complex subunit 6 (ORC6)
Identifiers
Symbol ORC6
Pfam PF05460
InterPro IPR008721

Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene.[1][2]

Background[edit]

The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins.

Function[edit]

The protein encoded by this gene is a subunit of the ORC complex. It has been shown that this protein and ORC1 are loosely associated with the core complex consisting of ORC2, -3, -4 and -5. Gene silencing studies with small interfering RNA demonstrated that this protein plays an essential role in coordinating chromosome replication and segregation with cytokinesis.[2]

Interactions[edit]

ORC6 has been shown to interact with MCM5,[3] ORC2,[3][4] Replication protein A1,[3] ORC4,[3] DBF4,[3] ORC3,[3][4] CDC45-related protein,[3] MCM4[3] and Cell division cycle 7-related protein kinase.[3]

References[edit]

  1. ^ Dhar SK, Dutta A (Nov 2000). "Identification and characterization of the human ORC6 homolog". J Biol Chem 275 (45): 34983–8. doi:10.1074/jbc.M006069200. PMID 10945994. 
  2. ^ a b "Entrez Gene: ORC6L origin recognition complex, subunit 6 like (yeast)". 
  3. ^ a b c d e f g h i Kneissl, Margot; Pütter Vera, Szalay Aladar A, Grummt Friedrich (Mar 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. (England) 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. ISSN 0022-2836. PMID 12614612. 
  4. ^ a b Vashee, S; Simancek P, Challberg M D, Kelly T J (Jul 2001). "Assembly of the human origin recognition complex". J. Biol. Chem. (United States) 276 (28): 26666–73. doi:10.1074/jbc.M102493200. ISSN 0021-9258. PMID 11323433. 


Further reading[edit]



This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Origin recognition complex". More...

Origin recognition complex Edit Wikipedia article

Origin recognition complex subunit 2
Identifiers
Symbol ORC2
Pfam PF04084
InterPro IPR007220
Origin recognition complex (ORC) subunit 3 N-terminus
Identifiers
Symbol ORC3_N
Pfam PF07034
InterPro IPR010748
Origin recognition complex subunit 6 (ORC6)
Identifiers
Symbol ORC6
Pfam PF05460
InterPro IPR008721
Potential role of Cdc6 at the initiation of DNA replication.[1]

In molecular biology, ORC or origin recognition complex is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes.[2][3][4] ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle.[5] ORC directs DNA replication throughout the genome and is required for its initiation.[6][7][8] ORC bound at replication origins serves as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-Mcm7 complex.[9][10][11] Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase.[12][13][14] Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase.[5][15][16][17]

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR).[6][7][8] ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers.[8][18][19]

Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity.[20] The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability.[11] The ATPase activity of Orc1 is involved in formation of the pre-RC.[21][22][23] ATP binding by Orc5 is crucial for the stability of ORC as a whole. Only the Orc1-5 subunits are required for origin binding; Orc6 is essential for maintenance of pre-RCs once formed.[24] Interactions within ORC suggest that Orc2-3-6 may form a core complex.[5]

References[edit]

  1. ^ Borlado LR, Méndez J (February 2008). "CDC6: from DNA replication to cell cycle checkpoints and oncogenesis". Carcinogenesis 29 (2): 237–43. doi:10.1093/carcin/bgm268. PMID 18048387. 
  2. ^ Origin Recognition Complex at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Dutta A, Bell SP (1997). "Initiation of DNA replication in eukaryotic cells". Annu. Rev. Cell Dev. Biol. 13: 293–332. doi:10.1146/annurev.cellbio.13.1.293. PMID 9442876. 
  4. ^ Chesnokov IN (2007). "Multiple functions of the origin recognition complex". Int. Rev. Cytol. 256: 69–109. doi:10.1016/S0074-7696(07)56003-1. PMID 17241905. 
  5. ^ a b c Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T (December 2007). "Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins". FEMS Yeast Res. 7 (8): 1263–9. doi:10.1111/j.1567-1364.2007.00298.x. PMID 17825065. 
  6. ^ a b Bell SP, Stillman B (May 1992). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature 357 (6374): 128–34. doi:10.1038/357128a0. PMID 1579162. 
  7. ^ a b Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (November 1995). "The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing". Cell 83 (4): 563–8. doi:10.1016/0092-8674(95)90096-9. PMID 7585959. 
  8. ^ a b c Gibson DG, Bell SP, Aparicio OM (June 2006). "Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae". Genes Cells 11 (6): 557–73. doi:10.1111/j.1365-2443.2006.00967.x. PMID 16716188. 
  9. ^ Rao H, Stillman B (March 1995). "The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators". Proc. Natl. Acad. Sci. U.S.A. 92 (6): 2224–8. doi:10.1073/pnas.92.6.2224. PMC 42456. PMID 7892251. 
  10. ^ Rowley A, Cocker JH, Harwood J, Diffley JF (June 1995). "Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC". EMBO J. 14 (11): 2631–41. PMC 398377. PMID 7781615. 
  11. ^ a b Speck C, Chen Z, Li H, Stillman B (November 2005). "ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA". Nat. Struct. Mol. Biol. 12 (11): 965–71. doi:10.1038/nsmb1002. PMC 2952294. PMID 16228006. 
  12. ^ Kelly TJ, Brown GW (2000). "Regulation of chromosome replication". Annu. Rev. Biochem. 69: 829–80. doi:10.1146/annurev.biochem.69.1.829. PMID 10966477. 
  13. ^ Bell SP, Dutta A (2002). "DNA replication in eukaryotic cells". Annu. Rev. Biochem. 71: 333–74. doi:10.1146/annurev.biochem.71.110601.135425. PMID 12045100. 
  14. ^ Stillman B (February 2005). "Origin recognition and the chromosome cycle". FEBS Lett. 579 (4): 877–84. doi:10.1016/j.febslet.2004.12.011. PMID 15680967. 
  15. ^ Weinreich M, Liang C, Chen HH, Stillman B (September 2001). "Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11211–7. doi:10.1073/pnas.201387198. PMC 58709. PMID 11572976. 
  16. ^ Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature 411 (6841): 1068–73. doi:10.1038/35082600. PMID 11429609. 
  17. ^ Archambault V, Ikui AE, Drapkin BJ, Cross FR (August 2005). "Disruption of mechanisms that prevent rereplication triggers a DNA damage response". Mol. Cell. Biol. 25 (15): 6707–21. doi:10.1128/MCB.25.15.6707-6721.2005. PMC 1190345. PMID 16024805. 
  18. ^ Triolo T, Sternglanz R (May 1996). "Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing". Nature 381 (6579): 251–3. doi:10.1038/381251a0. PMID 8622770. 
  19. ^ Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J (June 1997). "The origin recognition complex, SIR1, and the S phase requirement for silencing". Science 276 (5318): 1547–51. doi:10.1126/science.276.5318.1547. PMID 9171055. 
  20. ^ Klemm RD, Austin RJ, Bell SP (February 1997). "Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex". Cell 88 (4): 493–502. doi:10.1016/S0092-8674(00)81889-9. PMID 9038340. 
  21. ^ Klemm RD, Bell SP (July 2001). "ATP bound to the origin recognition complex is important for preRC formation". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8361–7. doi:10.1073/pnas.131006898. PMC 37444. PMID 11459976. 
  22. ^ Bowers JL, Randell JC, Chen S, Bell SP (December 2004). "ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication". Mol. Cell 16 (6): 967–78. doi:10.1016/j.molcel.2004.11.038. PMID 15610739. 
  23. ^ Randell JC, Bowers JL, Rodri­guez HK, Bell SP (January 2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Mol. Cell 21 (1): 29–39. doi:10.1016/j.molcel.2005.11.023. PMID 16387651. 
  24. ^ Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP (November 2006). "An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes". EMBO J. 25 (21): 5150–8. doi:10.1038/sj.emboj.7601391. PMC 1630405. PMID 17053779. 

Further reading[edit]

This article incorporates text from the public domain Pfam and InterPro IPR007220

This article incorporates text from the public domain Pfam and InterPro IPR010748

This article incorporates text from the public domain Pfam and InterPro IPR008721

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Origin recognition complex subunit 6 (ORC6) Provide feedback

This family consists of several eukaryotic origin recognition complex subunit 6 (ORC6) proteins. Despite differences in their structure and sequences among eukaryotic replicators, ORC is a conserved feature of replication initiation in all eukaryotes. ORC-related genes have been identified in organisms ranging from S. pombe to plants to humans. All DNA replication initiation is driven by a single conserved eukaryotic initiator complex termed he origin recognition complex (ORC). The ORC is a six protein complex. The function of ORC is reviewed in [1].

Literature references

  1. Bell SP; , Genes Dev 2002;16:659-672.: The origin recognition complex: from simple origins to complex functions. PUBMED:11914271 EPMC:11914271

  2. Collier TM, Coopwood TB, Treadaway JP; , Angiology. 1975;26:518-520.: Mesenteric thrombosis associated with oral contraceptives. PUBMED:1053592 EPMC:1053592

  3. Dhar SK, Dutta A; , J Biol Chem. 2000;275:34983-34988.: Identification and characterization of the human ORC6 homolog. PUBMED:10945994 EPMC:10945994


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008721

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded in yeast by ORC1-6 [PUBMED:17241905]. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle [PUBMED:17825065]. ORC directs DNA replication throughout the genome and is required for its initiation [PUBMED:1579162, PUBMED:7585959, PUBMED:16716188]. ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex [PUBMED:7892251, PUBMED:7781615, PUBMED:16228006]. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase [PUBMED:10966477, PUBMED:12045100, PUBMED:15680967]. Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase [PUBMED:17825065, PUBMED:11572976, PUBMED:11429609, PUBMED:16024805].

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) [PUBMED:1579162, PUBMED:7585959, PUBMED:16716188]. ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers [PUBMED:16716188, PUBMED:8622770, PUBMED:9171055].

Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity [PUBMED:9038340]. The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability [PUBMED:16228006]. The ATPase activity of Orc1 is involved in formation of the pre-RC [PUBMED:11459976, PUBMED:15610739, PUBMED:16387651]. ATP binding by Orc5 is crucial for the stability of ORC as a whole. Only the Orc1-5 subunits are required for origin binding; Orc6 is essential for maintenance of pre-RCs once formed [PUBMED:17053779]. Interactions within ORC suggest that Orc2-3-6 may form a core complex [PUBMED:17825065].

ORC homologues have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans [PUBMED:9442876].

This entry represents subunit 6, which directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; interacts with Spp1 and with trimethylated histone H3; phosphorylated by Cdc28 [PUBMED:11914271, PUBMED:14574415].

In Saccharomyces cerevisiae (Baker's yeast), both ends of the Orc6 interact with Cdt1 [PUBMED:18006685] and the N terminus mediates an interaction with the S-phase cyclin Clb5 [PUBMED:15105375].

Gene Ontology

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Seed source: Pfam-B_16189 (release 8.0)
Previous IDs: ORC6; ORC6_1;
Type: Family
Author: Moxon SJ
Number in seed: 28
Number in full: 219
Average length of the domain: 235.70 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 72.06 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.9 20.8
Noise cut-off 20.4 20.2
Model length: 353
Family (HMM) version: 8
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Structures

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