NARF

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IEA GO_REF:0000044	UNDECIDED	Summary: Nuclear localization is well established for the canonical NARF protein (Q9UHQ1). On J3KS48 this row comes from a UniProt subcellular-location statement that is itself ARBA-derived, not from any assay of this product. Reason: The localization claim is true of the NARF gene's canonical product: FLAG-tagged NARF is exclusively nuclear in HeLa cells, and endogenous NARF is in the nuclear fraction. J3KS48, however, is a 217-residue alternative gene-model product. Independent re-mapping shows it keeps canonical residues 1-128 and 174-258 and lacks 129-173 and nearly all of 259-456, including all of the small-subunit-like domain and most of the large-subunit-like domain. No nuclear localization signal or prelamin-A-binding region has been mapped in NARF, so we cannot tell whether the deletions keep the localization determinants. No experiment reports J3KS48 protein specifically. The Ser29 phosphopeptide behind the PE level lies in the shared N-terminus, so it cannot tell J3KS48 apart from canonical NARF. Because the donor is the same gene, a nuclear location is plausible, but it is not established for this truncated product, so I leave the row UNDECIDED rather than accept or remove it. PANTHER places canonical NARF in subfamily PTHR11615:SF124 (NUCLEAR PRELAMIN A RECOGNITION FACTOR). The PAINT node PTN002614243 propagates lamin binding and lamin filament to Q9UHQ1, but not to J3KS48. Supporting Evidence: PMID:10514485 When a FLAG epitope-tagged Narf is expressed in HeLa cells, it is exclusively nuclear and partially co-localizes with the nuclear lamina. file:human/NARF/NARF-deep-research-falcon.md nuclear/nuclear-lamina localization should remain the primary annotation file:human/NARF/NARF-bioinformatics/RESULTS-rereview.md J3KS48 lacks Q9UHQ1 129-173 (an internal 45-residue segment) and essentially all of 259-455. file:human/NARF/NARF-bioinformatics/RESULTS.md Selected J3KS48 has 217 residues; reference Q9UHQ1 has 456 residues.

GO Term

Evidence

Action

Reason

IEA
GO_REF:0000044

UNDECIDED

Summary: Nuclear localization is well established for the canonical NARF protein (Q9UHQ1). On J3KS48 this row comes from a UniProt subcellular-location statement that is itself ARBA-derived, not from any assay of this product.

Reason: The localization claim is true of the NARF gene's canonical product: FLAG-tagged NARF is exclusively nuclear in HeLa cells, and endogenous NARF is in the nuclear fraction. J3KS48, however, is a 217-residue alternative gene-model product. Independent re-mapping shows it keeps canonical residues 1-128 and 174-258 and lacks 129-173 and nearly all of 259-456, including all of the small-subunit-like domain and most of the large-subunit-like domain. No nuclear localization signal or prelamin-A-binding region has been mapped in NARF, so we cannot tell whether the deletions keep the localization determinants. No experiment reports J3KS48 protein specifically. The Ser29 phosphopeptide behind the PE level lies in the shared N-terminus, so it cannot tell J3KS48 apart from canonical NARF. Because the donor is the same gene, a nuclear location is plausible, but it is not established for this truncated product, so I leave the row UNDECIDED rather than accept or remove it. PANTHER places canonical NARF in subfamily PTHR11615:SF124 (NUCLEAR PRELAMIN A RECOGNITION FACTOR). The PAINT node PTN002614243 propagates lamin binding and lamin filament to Q9UHQ1, but not to J3KS48.

Supporting Evidence:

PMID:10514485

When a FLAG epitope-tagged Narf is expressed in HeLa cells, it is exclusively nuclear and partially co-localizes with the nuclear lamina.

file:human/NARF/NARF-deep-research-falcon.md

nuclear/nuclear-lamina localization should remain the primary annotation

file:human/NARF/NARF-bioinformatics/RESULTS-rereview.md

J3KS48 lacks Q9UHQ1 129-173 (an internal 45-residue segment) and essentially all of 259-455.

file:human/NARF/NARF-bioinformatics/RESULTS.md

Selected J3KS48 has 217 residues; reference Q9UHQ1 has 456 residues.

ProtNLM2 External predictions

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

The selected short NARF product has no demonstrated 4Fe–4S cluster binding. The accompanying function paragraph confuses NARF/IOP2 with the experimentally distinguished CIA paralog NARFL/IOP1.

Source documents: genes/human/NARF/NARF-protnlm-source.json · genes/human/NARF/NARF-notes.md

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

GO:0051539 4 iron, 4 sulfur cluster binding GO_MF

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-10 · file:human/NARF/NARF-protnlm-source.json

Review rationale: UNC. Neither J3KS48 nor the canonical NARF product Q9UHQ1 carries any iron-sulfur annotation in GOA, and no experiment has shown a bound Fe-S cluster in NARF, so the term would be novel but is unsupported. Hydrogenase-family (PTHR11615) homology makes cysteine-ligated cluster binding a hypothesis only; the family review keeps NARF/IOP2 distinct from NARFL/IOP1 and transfers no Fe-S term to NARF. A report of in vitro H2 production with a sequence-inferred [4Fe4S] cluster concerns recombinant IOP1/NARFL, not NARF, so it does not transfer across this paralog split. At the product level the required feature is unresolved. J3KS48 is a 217-residue product lacking much of the 456-residue reference, including Cys172, the C-terminal Cys374/Cys378 pair of the large-subunit-like domain and the whole small-subunit-like domain, so a complete hydrogenase-like cluster site is unlikely, but it keeps the N-terminal cysteine-rich region (12 of 15 cysteines), and no mapping establishes whether any cluster site in NARF depends only on the lost cysteines. The IOP2 knockdown result distinguishes CIA function but does not test cluster occupancy, so it neither validates nor refutes the claim.

Supporting Evidence:

file:human/NARF/NARF-bioinformatics/RESULTS.md: "Selected J3KS48 has 217 residues; reference Q9UHQ1 has 456 residues."
file:human/NARF/NARF-bioinformatics/RESULTS-rereview.md: "It loses Cys172 and the C-terminal Cys374/Cys378 pair inside PF02906, and all of PF02256."
file:human/NARF/NARF-bioinformatics/RESULTS-rereview.md: "J3KS48 keeps the N-terminal cysteine-rich region and roughly the first 40% of the hydrogenase-like large-subunit domain."
PMID:18270200: "Knockdown of IOP2, in contrast, had no effect on either."
PMID:40073536: "both HsIOP1 and SsCIAO3 may contain four conserved cysteine residues, forming a [4Fe4S] cluster"

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Bioinformatics Results

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Protnlm Function Review

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Gene Description

Existing Annotations Review

References

Suggested Questions for Experts

Suggested Experiments

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

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