Summary: Origin recognition complex subunit 2
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "ORC2". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
|Origin recognition complex, subunit 2|
|RNA expression pattern|
|Origin recognition complex subunit 2|
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. This protein forms a core complex with ORC3, ORC4, and ORC5. It also interacts with CDC45L and MCM10, which are proteins known to be important for the initiation of DNA replication. This protein has been demonstrated to specifically associate with the origin of replication of Epstein-Barr virus in human cells, and is thought to be required for DNA replication from viral origin of replication.
ORC2 has been shown to interact with ORC1, Replication protein A1, ORC4, ORC5, ORC3, MCM4, CDC6, MCM5, MCM6, MCM7, MCM10, DBF4, MCM2 and ORC6.
- Takahara K, Bong M, Brevard R, Eddy RL, Haley LL, Sait SJ, Shows TB, Hoffman GG, Greenspan DS (October 1996). "Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L". Genomics 31 (1): 119â122. doi:10.1006/geno.1996.0018. PMID 8808289.
- "Entrez Gene: ORC2L origin recognition complex, subunit 2-like (yeast)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4999.
- Kneissl, Margot; PÃ¼tter Vera, Szalay Aladar A, Grummt Friedrich (March 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. (England) 327 (1): 111â128. doi:10.1016/S0022-2836(03)00079-2. ISSN 0022-2836. PMID 12614612.
- Fujita, Masatoshi; Ishimi Yukio, Nakamura Hiromu, Kiyono Tohru, Tsurumi Tatsuya (March 2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells". J. Biol. Chem. (United States) 277 (12): 10354â10361. doi:10.1074/jbc.M111398200. ISSN 0021-9258. PMID 11779870.
- Vashee, S; Simancek P, Challberg M D, Kelly T J (July 2001). "Assembly of the human origin recognition complex". J. Biol. Chem. (United States) 276 (28): 26666â26673. doi:10.1074/jbc.M102493200. ISSN 0021-9258. PMID 11323433.
- MÃ©ndez, Juan; Zou-Yang X Helena, Kim So-Young, Hidaka Masumi, Tansey William P, Stillman Bruce (March 2002). "Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication". Mol. Cell (United States) 9 (3): 481â491. doi:10.1016/S1097-2765(02)00467-7. ISSN 1097-2765. PMID 11931757.
- Dhar, S K; Delmolino L, Dutta A (August 2001). "Architecture of the human origin recognition complex". J. Biol. Chem. (United States) 276 (31): 29067â29071. doi:10.1074/jbc.M103078200. ISSN 0021-9258. PMID 11395502.
- Quintana, D G; Hou Zh, Thome K C, Hendricks M, Saha P, Dutta A (November 1997). "Identification of HsORC4, a member of the human origin of replication recognition complex". J. Biol. Chem. (United States) 272 (45): 28247â28251. doi:10.1074/jbc.272.45.28247. ISSN 0021-9258. PMID 9353276.
- Quintana, D G; Thome K C, Hou Z H, Ligon A H, Morton C C, Dutta A (October 1998). "ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases". J. Biol. Chem. (United States) 273 (42): 27137â27145. doi:10.1074/jbc.273.42.27137. ISSN 0021-9258. PMID 9765232.
- 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): 1160â1166. doi:10.1126/science.1140321. PMID 17525332.
- Pinto, S; Quintana D G, Smith P, Mihalek R M, Hou Z H, Boynton S, Jones C J, Hendricks M, Velinzon K, Wohlschlegel J A, Austin R J, Lane W S, Tully T, Dutta A (May. 1999). "latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant". Neuron (United States) 23 (1): 45â54. doi:10.1016/S0896-6273(00)80752-7. ISSN 0896-6273. PMID 10402192.
- MÃ©ndez, J; Stillman B (November 2000). "Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis". Mol. Cell. Biol. (United States) 20 (22): 8602â8612. doi:10.1128/MCB.20.22.8602-8612.2000. ISSN 0270-7306. PMC 102165. PMID 11046155. //www.ncbi.nlm.nih.gov/pmc/articles/PMC102165/.
- Izumi, M; Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon K Y, Hurwitz J, Yatagai F, Hanaoka F (December 2000). "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. (ENGLAND) 28 (23): 4769â4777. doi:10.1093/nar/28.23.4769. PMC 115166. PMID 11095689. //www.ncbi.nlm.nih.gov/pmc/articles/PMC115166/.
 Further reading
- Gavin KA, Hidaka M, Stillman B (1996). "Conserved initiator proteins in eukaryotes". Science 270 (5242): 1667â1671. doi:10.1126/science.270.5242.1667. PMID 7502077.
- Quintana DG, Hou Zh, Thome KC et al. (1997). "Identification of HsORC4, a member of the human origin of replication recognition complex". J. Biol. Chem. 272 (45): 28247â28251. doi:10.1074/jbc.272.45.28247. PMID 9353276.
- Saha P, Thome KC, Yamaguchi R et al. (1998). "The human homolog of Saccharomyces cerevisiae CDC45". J. Biol. Chem. 273 (29): 18205â18209. doi:10.1074/jbc.273.29.18205. PMID 9660782.
- Ritzi M, Baack M, Musahl C et al. (1998). "Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin". J. Biol. Chem. 273 (38): 24543â24549. doi:10.1074/jbc.273.38.24543. PMID 9733749.
- Quintana DG, Thome KC, Hou ZH et al. (1998). "ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases". J. Biol. Chem. 273 (42): 27137â27145. doi:10.1074/jbc.273.42.27137. PMID 9765232.
- Pinto S, Quintana DG, Smith P et al. (1999). "latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant". Neuron 23 (1): 45â54. doi:10.1016/S0896-6273(00)80752-7. PMID 10402192.
- Jiang W, McDonald D, Hope TJ, Hunter T (1999). "Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication". EMBO J. 18 (20): 5703â5713. doi:10.1093/emboj/18.20.5703. PMC 1171637. PMID 10523313. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1171637/.
- Natale DA, Li CJ, Sun WH, DePamphilis ML (2000). "Selective instability of Orc1 protein accounts for the absence of functional origin recognition complexes during the M-G(1) transition in mammals". EMBO J. 19 (11): 2728â2738. doi:10.1093/emboj/19.11.2728. PMC 212765. PMID 10835370. //www.ncbi.nlm.nih.gov/pmc/articles/PMC212765/.
- 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): 35233â35241. doi:10.1074/jbc.M005765200. PMID 10954718.
- Izumi M, Yanagi K, Mizuno T et al. (2001). "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. 28 (23): 4769â4777. doi:10.1093/nar/28.23.4769. PMC 115166. PMID 11095689. //www.ncbi.nlm.nih.gov/pmc/articles/PMC115166/.
- Vashee S, Simancek P, Challberg MD, Kelly TJ (2001). "Assembly of the human origin recognition complex". J. Biol. Chem. 276 (28): 26666â26673. 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): 29067â29071. doi:10.1074/jbc.M103078200. PMID 11395502.
- Dhar SK, Yoshida K, Machida Y et al. (2001). "Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin". Cell 106 (3): 287â296. doi:10.1016/S0092-8674(01)00458-5. PMID 11509178.
- Izumi M, Yatagai F, Hanaoka F (2002). "Cell cycle-dependent proteolysis and phosphorylation of human Mcm10". J. Biol. Chem. 276 (51): 48526â31. doi:10.1074/jbc.M107190200. PMID 11602595.
- Fujita M, Ishimi Y, Nakamura H et al. (2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells". J. Biol. Chem. 277 (12): 10354â10361. doi:10.1074/jbc.M111398200. PMID 11779870.
- Schaarschmidt D, Ladenburger EM, Keller C, Knippers R (2002). "Human Mcm proteins at a replication origin during the G1 to S phase transition". Nucleic Acids Res. 30 (19): 4176â4185. doi:10.1093/nar/gkf532. PMC 140533. PMID 12364596. //www.ncbi.nlm.nih.gov/pmc/articles/PMC140533/.
- Matheos D, Ruiz MT, Price GB, Zannis-Hadjopoulos M (2002). "Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication". Biochim. Biophys. Acta 1578 (1â3): 59â72. doi:10.1016/S0167-4781(02)00497-9. PMID 12393188.
- 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): 16899â16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/.
- Kneissl M, PÃ¼tter 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): 111â128. doi:10.1016/S0022-2836(03)00079-2. PMID 12614612.
|This article on a gene on chromosome 2 is a stub. You can help Wikipedia by expanding it.|
This is the Wikipedia entry entitled "Origin recognition complex". More...
Does Pfam agree with the content of the Wikipedia entry ?
Editing Wikipedia articles
Before you edit for the first time
You should take a few minutes to view the following pages:
How your contribution will be recorded
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, MÃ©ndez J (February 2008). "CDC6: from DNA replication to cell cycle checkpoints and oncogenesis". Carcinogenesis 29 (2): 237â43. 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: 293â332. doi:10.1146/annurev.cellbio.13.1.293. PMID 9442876.
- Chesnokov IN (2007). "Multiple functions of the origin recognition complex". Int. Rev. Cytol. 256: 69â109. 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): 1263â9. 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): 128â34. 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): 563â8. 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): 557â73. 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): 2224â8. doi:10.1073/pnas.92.6.2224. PMC 42456. PMID 7892251. //www.ncbi.nlm.nih.gov/pmc/articles/PMC42456/.
- 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): 2631â41. PMC 398377. PMID 7781615. //www.ncbi.nlm.nih.gov/pmc/articles/PMC398377/.
- 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): 965â71. doi:10.1038/nsmb1002. PMC 2952294. PMID 16228006. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2952294/.
- Kelly TJ, Brown GW (2000). "Regulation of chromosome replication". Annu. Rev. Biochem. 69: 829â80. doi:10.1146/annurev.biochem.69.1.829. PMID 10966477.
- Bell SP, Dutta A (2002). "DNA replication in eukaryotic cells". Annu. Rev. Biochem. 71: 333â74. doi:10.1146/annurev.biochem.71.110601.135425. PMID 12045100.
- Stillman B (February 2005). "Origin recognition and the chromosome cycle". FEBS Lett. 579 (4): 877â84. 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): 11211â7. doi:10.1073/pnas.201387198. PMC 58709. PMID 11572976. //www.ncbi.nlm.nih.gov/pmc/articles/PMC58709/.
- Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature 411 (6841): 1068â73. 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): 6707â21. doi:10.1128/MCB.25.15.6707-6721.2005. PMC 1190345. PMID 16024805. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1190345/.
- Triolo T, Sternglanz R (May 1996). "Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing". Nature 381 (6579): 251â3. 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): 1547â51. 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): 493â502. 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): 8361â7. doi:10.1073/pnas.131006898. PMC 37444. PMID 11459976. //www.ncbi.nlm.nih.gov/pmc/articles/PMC37444/.
- 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): 967â78. doi:10.1016/j.molcel.2004.11.038. PMID 15610739.
- Randell JC, Bowers JL, RodriÂguez HK, Bell SP (January 2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Mol. Cell 21 (1): 29â39. 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): 5150â8. doi:10.1038/sj.emboj.7601391. PMC 1630405. PMID 17053779. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1630405/.
 Further reading
- 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 subunit 2 Provide feedback
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 .
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007220
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 2, which binds the origin of replication. It plays a role in chromosome replication and mating type transcriptional silencing.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||nucleus (GO:0005634)|
|origin recognition complex (GO:0000808)|
|Biological process||DNA replication (GO:0006260)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_7065 (release 7.3);|
|Author:||Wood V, Finn RD|
|Number in seed:||31|
|Number in full:||329|
|Average length of the domain:||306.80 aa|
|Average identity of full alignment:||30 %|
|Average coverage of the sequence by the domain:||59.16 %|
|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:||9|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
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.