ORC2 explained

Symbol:	ORC2
Origin recognition complex subunit 2
Pfam:	PF04084
Interpro:	IPR007220

Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans.^{[1] [2]}

Function

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.

Interactions

ORC2 has been shown to interact with:

• CDC6,^[3]
• DBF4,
• MCM10,^[4]
  • MCM2 MCM4,
• MCM5,
• MCM6,
• MCM7,
• ORC1,^{[5] [6] [7] [8]}
• ORC3,^{[5] [7] [9] [10]}
• ORC4,^{[5] [7] [11] [12]}
• ORC5,^{[5] [7] [11] [13]}
• ORC6,^{[5] [7]} and
• Replication protein A1.^[5]

Further reading

• Gavin KA, Hidaka M, Stillman B . Conserved initiator proteins in eukaryotes . Science . 270 . 5242 . 1667–1671 . 1996 . 7502077 . 10.1126/science.270.5242.1667 . 43633493 .
• Saha P, Thome KC, Yamaguchi R, Hou Z, Weremowicz S, Dutta A . The human homolog of Saccharomyces cerevisiae CDC45 . J. Biol. Chem. . 273 . 29 . 18205–18209 . 1998 . 9660782 . 10.1074/jbc.273.29.18205 . free .
• Ritzi M, Baack M, Musahl C, Romanowski P, Laskey RA, Knippers R . Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin . J. Biol. Chem. . 273 . 38 . 24543–24549 . 1998 . 9733749 . 10.1074/jbc.273.38.24543 . free .
• 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 . latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant . Neuron . 23 . 1 . 45–54 . 1999 . 10402192 . 10.1016/S0896-6273(00)80752-7 . 781511 . free .
• Jiang W, McDonald D, Hope TJ, Hunter T . Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication . EMBO J. . 18 . 20 . 5703–5713 . 1999 . 10523313 . 1171637 . 10.1093/emboj/18.20.5703 .
• Natale DA, Li CJ, Sun WH, DePamphilis ML . 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 . 2728–2738 . 2000 . 10835370 . 212765 . 10.1093/emboj/19.11.2728 .
• Thome KC, Dhar SK, Quintana DG, 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. . 275 . 45 . 35233–35241 . 2001 . 10954718 . 10.1074/jbc.M005765200 . free .
• Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F . 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 . 4769–4777 . 2001 . 11095689 . 115166 . 10.1093/nar/28.23.4769 .
• Vashee S, Simancek P, Challberg MD, Kelly TJ . Assembly of the human origin recognition complex . J. Biol. Chem. . 276 . 28 . 26666–26673 . 2001 . 11323433 . 10.1074/jbc.M102493200 . free .
• Dhar SK, Delmolino L, Dutta A . Architecture of the human origin recognition complex . J. Biol. Chem. . 276 . 31 . 29067–29071 . 2001 . 11395502 . 10.1074/jbc.M103078200 . free .
• Dhar SK, Yoshida K, Machida Y, Khaira P, Chaudhuri B, Wohlschlegel JA, Leffak M, Yates J, Dutta A . Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin . Cell . 106 . 3 . 287–296 . 2001 . 11509178 . 10.1016/S0092-8674(01)00458-5 . 12479646 . free .
• Izumi M, Yatagai F, Hanaoka F . Cell cycle-dependent proteolysis and phosphorylation of human Mcm10 . J. Biol. Chem. . 276 . 51 . 48526–31 . 2002 . 11602595 . 10.1074/jbc.M107190200 . free .
• Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T . Nuclear organization of DNA replication initiation proteins in mammalian cells . J. Biol. Chem. . 277 . 12 . 10354–10361 . 2002 . 11779870 . 10.1074/jbc.M111398200 . free .
• Schaarschmidt D, Ladenburger EM, Keller C, Knippers R . Human Mcm proteins at a replication origin during the G1 to S phase transition . Nucleic Acids Res. . 30 . 19 . 4176–4185 . 2002 . 12364596 . 140533 . 10.1093/nar/gkf532 .
• Matheos D, Ruiz MT, Price GB, Zannis-Hadjopoulos M . Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication . Biochim. Biophys. Acta . 1578 . 1–3 . 59–72 . 2002 . 12393188 . 10.1016/S0167-4781(02)00497-9 .
• Kneissl M, Pütter V, Szalay AA, Grummt F . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . J. Mol. Biol. . 327 . 1 . 111–128 . 2003 . 12614612 . 10.1016/S0022-2836(03)00079-2 .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Origin recognition complex subunit 2 (ORC2)

Notes and References

1. Takahara K, Bong M, Brevard R, Eddy RL, Haley LL, Sait SJ, Shows TB, Hoffman GG, Greenspan DS . 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 . 119–122 . October 1996 . 8808289 . 10.1006/geno.1996.0018 .
2. Web site: Entrez Gene: ORC2L origin recognition complex, subunit 2-like (yeast).
3. Méndez J, Stillman B . 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. . 20 . 22 . 8602–12 . November 2000 . 11046155 . 102165 . 10.1128/mcb.20.22.8602-8612.2000.
4. Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F . 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 . 4769–77 . December 2000 . 11095689 . 115166 . 10.1093/nar/28.23.4769.
5. Kneissl M, Pütter V, Szalay AA, Grummt F . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . J. Mol. Biol. . 327 . 1 . 111–28 . March 2003 . 12614612 . 10.1016/s0022-2836(03)00079-2.
6. Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T . Nuclear organization of DNA replication initiation proteins in mammalian cells . J. Biol. Chem. . 277 . 12 . 10354–61 . March 2002 . 11779870 . 10.1074/jbc.M111398200 . free .
7. Vashee S, Simancek P, Challberg MD, Kelly TJ . Assembly of the human origin recognition complex . J. Biol. Chem. . 276 . 28 . 26666–73 . July 2001 . 11323433 . 10.1074/jbc.M102493200 . free .
8. Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B . Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication . Mol. Cell . 9 . 3 . 481–91 . March 2002 . 11931757 . 10.1016/s1097-2765(02)00467-7. free .
9. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage . Science . 316 . 5828 . 1160–6 . May 2007 . 17525332 . 10.1126/science.1140321 . 2007Sci...316.1160M . 16648052 .
10. 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 . latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant . Neuron . 23 . 1 . 45–54 . May 1999 . 10402192 . 10.1016/s0896-6273(00)80752-7. 781511 . free .
11. Dhar SK, Delmolino L, Dutta A . Architecture of the human origin recognition complex . J. Biol. Chem. . 276 . 31 . 29067–71 . August 2001 . 11395502 . 10.1074/jbc.M103078200 . free .
12. Quintana DG, ((Hou Zh)), Thome KC, Hendricks M, Saha P, Dutta A . Identification of HsORC4, a member of the human origin of replication recognition complex . J. Biol. Chem. . 272 . 45 . 28247–51 . November 1997 . 9353276 . 10.1074/jbc.272.45.28247. free .
13. Quintana DG, Thome KC, ((Hou Zh)), Ligon AH, Morton CC, Dutta A . ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases . J. Biol. Chem. . 273 . 42 . 27137–45 . October 1998 . 9765232 . 10.1074/jbc.273.42.27137. free .