Pathway Human Homo sapiens

Activation of the pre-replicative complex

R-HSA-68962 in Reactome release 97: under 2 parents, with 33 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-68962 (mouse), R-RNO-68962 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-68962.6
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2004-07-06
Last updated: 2021-12-08
Events inside: 9, counted from the record

In S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding by Orc1 is unaffected by the association of ORC with origin DNA (ARS) sequences, but ATP hydrolysis is ARS-dependent, being suppressed by associated double-stranded DNA and stimulated by associated single-stranded DNA. These data are consistent with the hypothesis that ORC functions as an ATPase switch, hydrolyzing bound ATP and changing state as DNA unwinds at the origin immediately before replication. It is attractive to speculate that ORC likewise functions as a switch as human pre-replicative complexes are activated, but human Orc proteins are not well enough characterized to allow the model to be critically tested. mRNAs encoding human orthologs of all six Orc proteins have been cloned, and ATP-binding amino acid sequence motifs have been identified in Orc1, Orc4, and Orc5. Interactions among proteins expressed from the cloned genes have been characterized, but the ATP-binding and hydrolyzing properties of these proteins and complexes of them have not been determined.

Literature Reactome attaches

ATP bound to the origin recognition complex is important for preRC formation.Proc Natl Acad Sci U S A, 2001, vol. 98, p. 8361-7PubMed 11459976
ATPase switches controlling DNA replication initiation.Curr Opin Cell Biol, 2000, vol. 12, p. 280-5PubMed 10801458
Architecture of the human origin recognition complex.J Biol Chem, 2001, vol. 276, p. 29067-71PubMed 11395502
Assembly of the human origin recognition complex.J Biol Chem, 2001, vol. 276, p. 26666-73PubMed 11323433
Conserved initiator proteins in eukaryotes.Science, 1996, vol. 270, p. 1667-71PubMed 7502077
Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex.Cell, 1997, vol. 88, p. 493-502PubMed 9038340
Identification of HsORC4, a member of the human origin of replication recognition complex.J Biol Chem, 1997, vol. 272, p. 28247-51PubMed 9353276
Nuclear organization of DNA replication initiation proteins in mammalian cells.J Biol Chem, 2002, vol. 277, p. 10354-61PubMed 11779870
ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases.J Biol Chem, 1998, vol. 273, p. 27137-45PubMed 9765232
Orc6 involved in DNA replication, chromosome segregation, and cytokinesis.Science, 2002, vol. 297, p. 1026-31PubMed 12169736
Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding.EMBO J, 2000, vol. 19, p. 4774-82PubMed 10970868
The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p.J Biol Chem, 1999, vol. 273, p. 32421-9PubMed 9829972
latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant.Neuron, 1999, vol. 23, p. 45-54PubMed 10402192

Reactome's record lists 14 orthologous events, R-RNO-68962 (Rattus norvegicus), R-MMU-68962 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"Activation of the pre-replicative complex". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-68962 with StableID: R-HSA-68962.6 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 33 genes in this human pathway; showing 1 to 33, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneCDC45	AuthorityHGNC:1739	Mapping file id8318 NCBI file	EvidenceTAS
GeneCDC6	AuthorityHGNC:1744	Mapping file id990 NCBI file	EvidenceTAS
GeneCDC7	AuthorityHGNC:1745	Mapping file id8317 NCBI file	EvidenceTAS
GeneCDK2	AuthorityHGNC:1771	Mapping file id1017 NCBI file	EvidenceTAS
GeneCDT1	AuthorityHGNC:24576	Mapping file id81620 NCBI file	EvidenceTAS
GeneDBF4	AuthorityHGNC:17364	Mapping file id10926 NCBI file	EvidenceTAS
GeneGMNN	AuthorityHGNC:17493	Mapping file id51053 NCBI file	EvidenceTAS
GeneMCM10	AuthorityHGNC:18043	Mapping file id55388 NCBI file	EvidenceTAS
GeneMCM2	AuthorityHGNC:6944	Mapping file id4171 NCBI file	EvidenceTAS
GeneMCM3	AuthorityHGNC:6945	Mapping file id4172 NCBI file	EvidenceTAS
GeneMCM4	AuthorityHGNC:6947	Mapping file id4173 NCBI file	EvidenceTAS
GeneMCM5	AuthorityHGNC:6948	Mapping file id4174 NCBI file	EvidenceTAS
GeneMCM6	AuthorityHGNC:6949	Mapping file id4175 NCBI file	EvidenceTAS
GeneMCM7	AuthorityHGNC:6950	Mapping file id4176 NCBI file	EvidenceTAS
GeneMCM8	AuthorityHGNC:16147	Mapping file id84515 NCBI file	EvidenceTAS
GeneORC1	AuthorityHGNC:8487	Mapping file id4998 NCBI file	EvidenceTAS
GeneORC2	AuthorityHGNC:8488	Mapping file id4999 NCBI file	EvidenceTAS
GeneORC3	AuthorityHGNC:8489	Mapping file id23595 NCBI file	EvidenceTAS
GeneORC4	AuthorityHGNC:8490	Mapping file id5000 NCBI file	EvidenceTAS
GeneORC5	AuthorityHGNC:8491	Mapping file id5001 NCBI file	EvidenceTAS
GeneORC6	AuthorityHGNC:17151	Mapping file id23594 NCBI file	EvidenceTAS
GenePOLA1	AuthorityHGNC:9173	Mapping file id5422 NCBI file	EvidenceTAS
GenePOLA2	AuthorityHGNC:30073	Mapping file id23649 NCBI file	EvidenceTAS
GenePOLE	AuthorityHGNC:9177	Mapping file id5426 NCBI file	EvidenceTAS
GenePOLE2	AuthorityHGNC:9178	Mapping file id5427 NCBI file	EvidenceTAS
GenePOLE3	AuthorityHGNC:13546	Mapping file id54107 NCBI file	EvidenceTAS
GenePOLE4	AuthorityHGNC:18755	Mapping file id56655 NCBI file	EvidenceTAS
GenePRIM1	AuthorityHGNC:9369	Mapping file id5557 NCBI file	EvidenceTAS
GenePRIM2	AuthorityHGNC:9370	Mapping file id5558 NCBI file	EvidenceTAS
GeneRPA1	AuthorityHGNC:10289	Mapping file id6117 NCBI file	EvidenceTAS
GeneRPA2	AuthorityHGNC:10290	Mapping file id6118 NCBI file	EvidenceTAS
GeneRPA3	AuthorityHGNC:10291	Mapping file id6119 NCBI file	EvidenceTAS
GeneRPA4	AuthorityHGNC:30305	Mapping file id29935 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.