Summary: Origin recognition complex (ORC) subunit 3 N-terminus
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|Origin recognition complex (ORC) subunit 3 N-terminus|
|Origin recognition complex, subunit 3|
|RNA expression pattern|
The origin recognition complex (ORC) is a highly conserved six subunits 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. The protein encoded by this gene is a subunit of the ORC complex. Studies of a similar gene in Drosophila suggested a possible role of this protein in neuronal proliferation and olfactory memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene.
- Tugal T, Zou-Yang XH, Gavin K, Pappin D, Canas B, Kobayashi R, Hunt T, Stillman B (Jan 1999). "The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p". J Biol Chem 273 (49): 32421–9. doi:10.1074/jbc.273.49.32421. PMID 9829972.
- Pinto S, Quintana DG, Smith P, Mihalek RM, Hou ZH, Boynton S, Jones CJ, Hendricks M, Velinzon K, Wohlschlegel JA, Austin RJ, Lane WS, Tully T, Dutta A (Jul 1999). "latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant". Neuron 23 (1): 45–54. doi:10.1016/S0896-6273(00)80752-7. PMID 10402192.
- "Entrez Gene: ORC3L origin recognition complex, subunit 3-like (yeast)".
- 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.
- Dhar, S K; Delmolino L, Dutta A (Aug 2001). "Architecture of the human origin recognition complex". J. Biol. Chem. (United States) 276 (31): 29067–71. doi:10.1074/jbc.M103078200. ISSN 0021-9258. PMID 11395502.
- Matsuoka, Shuhei; Ballif Bryan A, Smogorzewska Agata, McDonald E Robert, Hurov Kristen E, Luo Ji, Bakalarski Corey E, Zhao Zhenming, Solimini Nicole, Lerenthal Yaniv, Shiloh Yosef, Gygi Steven P, Elledge Stephen J (May 2007). "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage". Science (United States) 316 (5828): 1160–6. doi:10.1126/science.1140321. PMID 17525332.
- 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.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Springer J, Nanda I, Hoehn K et al. (2000). "Identification and chromosomal localization of murine ORC3, a new member of the mouse origin recognition complex". Cytogenet. Cell Genet. 87 (3–4): 245–51. doi:10.1159/000015435. PMID 10702681.
- Thome KC, Dhar SK, Quintana DG et al. (2001). "Subsets of human origin recognition complex (ORC) subunits are expressed in non-proliferating cells and associate with non-ORC proteins". J. Biol. Chem. 275 (45): 35233–41. doi:10.1074/jbc.M005765200. PMID 10954718.
- Wiemann S, Weil B, Wellenreuther R et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Vashee S, Simancek P, Challberg MD, Kelly TJ (2001). "Assembly of the human origin recognition complex". J. Biol. Chem. 276 (28): 26666–73. doi:10.1074/jbc.M102493200. PMID 11323433.
- Dhar SK, Delmolino L, Dutta A (2001). "Architecture of the human origin recognition complex". J. Biol. Chem. 276 (31): 29067–71. doi:10.1074/jbc.M103078200. PMID 11395502.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Kneissl M, Pütter V, Szalay AA, Grummt F (2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. PMID 12614612.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Ramachandran N, Hainsworth E, Bhullar B et al. (2004). "Self-assembling protein microarrays". Science 305 (5680): 86–90. doi:10.1126/science.1097639. PMID 15232106.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Sibani S, Price GB, Zannis-Hadjopoulos M (2005). "Ku80 binds to human replication origins prior to the assembly of the ORC complex". Biochemistry 44 (21): 7885–96. doi:10.1021/bi047327n. PMID 15910003.
- Matsuoka S, Ballif BA, Smogorzewska A et al. (2007). "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage". Science 316 (5828): 1160–6. doi:10.1126/science.1140321. PMID 17525332.
|This article on a gene on chromosome 6 is a stub. You can help Wikipedia by expanding it.|
This is the Wikipedia entry entitled "Origin recognition complex". More...
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Origin recognition complex Edit Wikipedia article
|Origin recognition complex subunit 2|
|Origin recognition complex (ORC) subunit 3 N-terminus|
|Origin recognition complex subunit 6 (ORC6)|
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. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle. ORC directs DNA replication throughout the genome and is required for its initiation. 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. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase. 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.
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). 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.
Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity. The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability. The ATPase activity of Orc1 is involved in formation of the pre-RC. 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. Interactions within ORC suggest that Orc2-3-6 may form a core complex.
- 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.
- Origin Recognition Complex at the US National Library of Medicine Medical Subject Headings (MeSH)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Stephen P. Bell and Anindya Dutta, DNA REPLICATION IN EUKARYOTIC CELLS, Annual Review of Biochemistry, 2002. doi:10.1146/annurev.biochem.71.110601.135425. A comprehensive review of molecular DNA replication.
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 (ORC) subunit 3 N-terminus Provide feedback
This family represents the N-terminus (approximately 300 residues) of subunit 3 of the eukaryotic origin recognition complex (ORC). Origin recognition complex (ORC) is composed of six subunits that are essential for cell viability. They collectively bind to the autonomously replicating sequence (ARS) in a sequence-specific manner and lead to the chromatin loading of other replication factors that are essential for initiation of DNA replication .
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR020795
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].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||nuclear origin of replication recognition complex (GO:0005664)|
|Molecular function||DNA binding (GO:0003677)|
|Biological process||DNA replication (GO:0006260)|
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|Seed source:||Pfam-B_10452 (release 10.0)|
|Author:||Vella Briffa B|
|Number in seed:||13|
|Number in full:||289|
|Average length of the domain:||270.20 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||40.30 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.