ORC5

UniProt ID: A0A9L0JAR4
Organism: Equus asinus
Review Status: COMPLETE
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Gene Description

ORC5 is a subunit of the six-subunit origin recognition complex (ORC1-6), the AAA+ ATPase assembly that binds DNA replication origins in the nucleus and, with CDC6 and CDT1, loads the MCM2-7 helicase to form the pre-replication complex that licenses origins for replication initiation. ORC5 has an N-terminal AAA+-like ATPase domain with a Walker A P-loop, a lid domain and a C-terminal winged-helix domain whose beta-hairpin lies next to origin DNA; ATP binding by ORC5 is needed for assembly of human ORC, and ORC5 forms part of the stable ORC2-5 core. In human cells chromatin-bound ORC5 is multi-mono-ubiquitylated by OBI1 in S phase, which promotes origin firing. The donkey product A0A9L0JAR4 (440 aa) is one of several Ensembl transcript products of the single donkey ORC5 gene; it matches human ORC5 over residues 1-421, including the P-loop and the DNA-proximal hairpin, but ends in a 19-residue alternative C-terminal segment in place of the conserved 14-residue mammalian ORC5 C-terminus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000808 origin recognition complex
IEA
GO_REF:0000002 		ACCEPT
Summary: ORC5 is a core subunit of the origin recognition complex.
Reason: Human ORC5 is one of the six ORC subunits and forms part of the stable ORC2-5 core seen by cryo-EM. A0A9L0JAR4 is a product of the single donkey ORC5 gene (PTHR12705:SF0, the only subfamily of this one-subunit family, which also holds human, yeast and plant ORC5), and is identical in architecture to human ORC5 over residues 1-421 (AAA+ domain, lid and winged-helix). Its alternative C-terminus replaces only the last 14 residues of the canonical protein, so complex membership is expected to be retained, although no product-specific test exists.
Supporting Evidence:
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6.
PMID:32808929
The absence of ORC1 revealed a compact, stable complex of ORC2-5.
file:EQUAS/ORC5/ORC5-bioinformatics/RESULTS-rereview.md
Human ORC5 Walker A (residues 37-44) GHTASGKT vs A0A9L0JAR4 GHTASGKT; human DNA-proximal beta-hairpin H398 vs A0A9L0JAR4 residue 398 H.
GO:0003688 DNA replication origin binding
IEA
GO_REF:0000118 		ACCEPT
Summary: ORC binds replication origins; ORC5 contributes DNA-proximal surfaces to the complex.
Reason: Origin binding is a property of the ORC assembly, to which ORC5 contributes: human ORC structures place positively charged regions of ORC1-5 next to the bound DNA and identify the ORC5-ORC3 interface as a hinge for DNA binding; the ORC5 winged-helix beta-hairpin places H398 next to DNA. A0A9L0JAR4 conserves the P-loop and H398 and is unchanged from human over residues 1-421. ORC5 has no origin binding activity on its own: the activity belongs to the complex, which ORC5 contributes to. Accepted on that basis (core_functions records it as contributes_to). The TreeGrafter node also carries this term for the whole subfamily.
Supporting Evidence:
PMID:32808929
The Ξ²-hairpin loop in ORC5 of HsORC also consists of a positively-charged residue H398 in close proximity to DNA
file:EQUAS/ORC5/ORC5-bioinformatics/RESULTS-rereview.md
Human ORC5 Walker A (residues 37-44) GHTASGKT vs A0A9L0JAR4 GHTASGKT; human DNA-proximal beta-hairpin H398 vs A0A9L0JAR4 residue 398 H.
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
Component of the origin recognition complex (ORC) that binds origins of replication.
PMID:32808929
ORC subunits 1–5 contain regions with positively-charged residues proximal to the DNA.
PMID:32808929
revealing a hinge at the ORC5Β·ORC3 interface that may facilitate ORC binding to DNA
GO:0005634 nucleus
IEA
GO_REF:0000120 		ACCEPT
Summary: ORC5 is a nuclear protein.
Reason: Human ORC5 localizes to the nucleus and chromatin (PMID:31160578), consistent with its replication-origin role; the donkey gene is its one-to-one ortholog.
Supporting Evidence:
PMID:31160578
Altogether, these results showed that chromatin-bound ORC3/5 become multi-mono-ubiquitylated concomitantly with origin firing.
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
Nucleus {ECO:0000269|PubMed:31160578}.
GO:0005664 nuclear origin of replication recognition complex
IEA
GO_REF:0000118 		ACCEPT
Summary: Nuclear origin of replication recognition complex is the specific complex term for eukaryotic ORC.
Reason: The specific eukaryotic ORC term, transferred by TreeGrafter from the PANTHER PTHR12705 node; human ORC5 is an experimentally established subunit of nuclear ORC and the donkey gene is its one-to-one ortholog in the same (single) PANTHER subfamily. Retained for this alternative-C-terminus product on the same basis as the ORC row.
Supporting Evidence:
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6.
PMID:32808929
The absence of ORC1 revealed a compact, stable complex of ORC2-5.
file:EQUAS/ORC5/ORC5-bioinformatics/RESULTS-rereview.md
Human ORC5 Walker A (residues 37-44) GHTASGKT vs A0A9L0JAR4 GHTASGKT; human DNA-proximal beta-hairpin H398 vs A0A9L0JAR4 residue 398 H.
GO:0006260 DNA replication
IEA
GO_REF:0000120 		TOO GENERAL
Summary: DNA replication is correct but entailed by the accepted DNA replication initiation.
Reason: ORC acts at the initiation step of DNA replication; DNA replication initiation is the informative process.
Supporting Evidence:
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
GO:0006270 DNA replication initiation
IEA
GO_REF:0000118 		ACCEPT
Summary: DNA replication initiation is the core process: ORC loads the pre-replication complex at origins.
Reason: ORC5, as an ORC subunit, participates directly in origin recognition and pre-RC assembly that license replication initiation.
Supporting Evidence:
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
Component of the origin recognition complex (ORC) that binds origins of replication.

Core Functions

Subunit of the nuclear origin recognition complex. As part of the ATP-dependent ORC2-5 core, ORC5 contributes to origin DNA binding by the complex (through its winged-helix beta-hairpin) and to the ORC platform on which the pre-replication complex is assembled for DNA replication initiation.

Directly Involved In:
DNA replication initiation
Cellular Locations:
nucleus
In Complex:
nuclear origin of replication recognition complex
Supporting Evidence:
  • file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
    Component of the origin recognition complex (ORC) that binds origins of replication.
  • file:EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt
    ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
  • PMID:32808929
    ORC subunits 1–5 contain regions with positively-charged residues proximal to the DNA.
  • PMID:17716973
    Mutations in the ATP-binding sites of Orc4 or Orc5
  • file:EQUAS/ORC5/ORC5-bioinformatics/RESULTS-rereview.md
    Human ORC5 Walker A (residues 37-44) GHTASGKT vs A0A9L0JAR4 GHTASGKT; human DNA-proximal beta-hairpin H398 vs A0A9L0JAR4 residue 398 H.

References

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Suggested Questions for Experts

Q: Is the A0A9L0JAR4 transcript, with its alternative C-terminal segment (residues 422-440), expressed in donkey tissues, or is it a gene-model artefact? The full-length canonical-type product is A0A9L0I6Y4.

Q: Should ORC5 carry an ATP binding molecular function term, given that its Walker A motif is required for ATP-dependent assembly of human ORC?

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML Β· ORC5-protnlm-predictions-review.yaml Β· Review status: COMPLETE

Assessment of 2 ProtNLM2 GO predictions for donkey ORC5 product A0A9L0JAR4 (440 aa), one of several products of the single donkey ORC5 gene. It matches human ORC5 over residues 1-421 (AAA+ domain with the Walker A P-loop, lid, and winged-helix with the DNA-proximal H398 hairpin) and ends in a 19-residue alternative C-terminal segment in place of the conserved 14-residue mammalian C-terminus; no known ORC5 activity or localization signal maps to those 14 residues. Nucleus is correct for this product and already in donkey GOA (CNN). DNA replication is correct but less precise than the DNA replication initiation annotation already in GOA (LSP). ProtNLM2 also emitted non-GO function text for this accession ("Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent ... ORC is required to assemble the pre-replication complex necessary to initiate DNA replication"), which closely mirrors the existing ARBA function text of the donkey record and is not scored here.

Source documents: projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv Β· genes/EQUAS/ORC5/ORC5-uniprot.txt Β· genes/EQUAS/ORC5/ORC5-goa.tsv Β· genes/EQUAS/ORC5/ORC5-bioinformatics/human_O43913-uniprot.txt Β· genes/EQUAS/ORC5/ORC5-bioinformatics/RESULTS.md Β· genes/EQUAS/ORC5/ORC5-bioinformatics/RESULTS-rereview.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0006260 DNA replication GO_BP
LSP β€” Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-10-14
Review rationale: Human ORC5 is a subunit of ORC, which binds origins and is required to assemble the pre-replication complex that initiates DNA replication. This product, A0A9L0JAR4, keeps the AAA+ domain with the Walker A P-loop (GHTASGKT), the lid and the winged-helix with the DNA-proximal H398, matching human ORC5 at 402 of residues 1-420; it lacks only the last 14 residues of the canonical C-terminus, which are replaced by an alternative segment and have no known role in ORC assembly or replication. DNA replication is therefore correct for this product. Donkey GOA contains this exact term (combined IEA) and the more specific descendant DNA replication initiation (TreeGrafter), so the prediction is less precise than an existing annotation.
Supporting Evidence:
GO:0005634 nucleus GO_CC
CNN β€” Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-10-14
Review rationale: Human ORC5 is experimentally localized to the nucleus and chromatin (PMID:9765232; PMID:31160578 via UniProt), and ORC acts on nuclear replication origins. Human ORC5 has no annotated nuclear localization signal in its C-terminal 14 residues, the only canonical region this product A0A9L0JAR4 lacks; it retains the AAA+, lid and winged-helix regions that build the ORC2-5 core, so nuclear localization is expected for this product. The exact term is already in donkey GOA (combined IEA), so the prediction is correct but not novel.
Supporting Evidence:

Deep Research

Cyberian

(ORC5-deep-research-cyberian.md)

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πŸ“š Additional Documentation

Notes

(ORC5-notes.md)

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Bioinformatics Results

(RESULTS.md)

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πŸ“„ View Raw YAML

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