A2FPI7

UniProt ID: A2FPI7
Organism: Trichomonas vaginalis G3
Review Status: DRAFT
Aliases:
TVAG_233530 TVAG_559790
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Gene Description

A2FPI7 (ORFs TVAG_233530 and TVAG_559790, two identical loci in the G3 draft assembly) is a predicted 129-amino-acid protein of the parabasalid parasite Trichomonas vaginalis that consists almost entirely of a single KilA-N domain (residues ~19-127). KilA-N is a winged helix-turn-helix-like module first defined in proteins of large bacterial and eukaryotic DNA viruses and proposed to be a DNA-binding domain; it shares a fold with, and is the likely viral ancestor of, the APSES DNA-binding domain of fungal transcription factors such as yeast Mbp1 and Swi4. A2FPI7 belongs to PANTHER family PTHR48135, a KilA-N lineage of bacteria and phages that has undergone a massive lineage-specific expansion in T. vaginalis (over 1,300 of ~1,670 family members are T. vaginalis proteins); it is not an ortholog of the characterised fungal APSES factors, and no member of its family has been studied experimentally. A2FPI7 is therefore best described as a probable, uncharacterised DNA-binding protein; its binding specificity, subcellular location, targets and biological role are unknown, and the protein has not been detected experimentally (UniProt protein existence level 4, predicted).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003677 DNA binding
ISM
file:TRIV3/A2FPI7/A2FPI7-uniprot.txt 		NEW
Summary: GOA has no annotations for A2FPI7; this row is a proposed annotation. A2FPI7 is a stand-alone KilA-N domain (Pfam PF04383 24-126, SMART SM01252 28-127, PROSITE PS51301 19-124). Iyer et al. (2002) defined KilA-N as a conserved DNA-binding domain of viral regulators and argued from fold-level evidence that it is homologous to the fungal APSES DNA-binding domain, whose DNA binding is experimentally established (Mbp1 crystal structure and MCB-binding assays; see genes/yeast/MBP1). A2FPI7's own family (PTHR48135, a phage/bacterial KilA-N lineage expanded in T. vaginalis) contains no experimentally characterised member, and A2FPI7 has no pairwise-detectable similarity to the Mbp1 APSES domain (z = 1.25), though it is clearly similar to the phage P1 KilA KilA-N region (z = 7.4).
Reason: Kept as a proposed, domain-level molecular function. DNA binding is the one property attributed to the whole KilA-N/APSES superfamily rather than to a particular subfamily, and the A2FPI7 protein is nothing but that domain, so the general term is appropriate and nothing more specific (sequence-specific binding, cis-regulatory region binding, transcription factor activity) is transferable: those properties are established only in the fungal APSES families PTHR43828/PTHR47792, which A2FPI7 does not belong to. Confidence is moderate; the inference rests on superfamily homology, not on an experimental member of PTHR48135. The previous version of this row also cited a machine-learning prediction; that has been dropped and is not used as evidence.
Supporting Evidence:
PMID:11897024
the amino-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses
PMID:11897024
The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain.
file:TRIV3/A2FPI7/A2FPI7-uniprot.txt
/note="KilA-N"
file:TRIV3/A2FPI7/A2FPI7-bioinformatics/RESULTS.md
DNA binding is a domain-level (superfamily fold) inference; no member of PTHR48135 has experimental evidence of DNA binding or of any other molecular function.

Core Functions

Probable DNA binding through a stand-alone KilA-N domain, inferred at the superfamily level (KilA-N/APSES fold). Binding specificity, partners and any regulatory role are unknown; no member of the A2FPI7 PANTHER family (PTHR48135) has been characterised experimentally, so subfamily-specific APSES functions are not transferred.

Molecular Function:
DNA binding
Supporting Evidence:
  • PMID:11897024
    The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain.
  • file:TRIV3/A2FPI7/A2FPI7-bioinformatics/RESULTS.md
    DNA binding is a domain-level (superfamily fold) inference; no member of PTHR48135 has experimental evidence of DNA binding or of any other molecular function.

References

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Suggested Questions for Experts

Q: Is A2FPI7 (TVAG_233530/TVAG_559790) expressed at the protein level in T. vaginalis, and where in the cell does it localize?

Q: Do the >1,300 PTHR48135 KilA-N proteins of T. vaginalis derive from a single lateral transfer from a phage or bacterium followed by expansion, and are they associated with transposable elements or viral-like genomic segments?

Q: Does the A2FPI7 KilA-N domain bind double-stranded DNA, and if so with any sequence preference, given that the only experimentally characterised KilA-N-fold domains are the fungal APSES domains in different PANTHER families?

Suggested Experiments

Experiment: Express recombinant A2FPI7 and test DNA binding by EMSA with random and designed probes, followed by SELEX or protein-binding microarray if binding is observed; mutate the predicted recognition helix as a control.

Hypothesis: A2FPI7 binds double-stranded DNA via its KilA-N domain.

Type: EMSA

Experiment: Express epitope-tagged A2FPI7 in T. vaginalis and determine localization by immunofluorescence with DAPI co-staining.

Hypothesis: A2FPI7 localizes to the T. vaginalis nucleus.

Type: fluorescence microscopy

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 · A2FPI7-protnlm-predictions-review.yaml · Review status: COMPLETE

The nearly complete KilA-N DNA-binding domain supports a broad DNA-binding inference without specifying a regulatory target.

Source documents: genes/TRIV3/A2FPI7/A2FPI7-uniprot.txt · genes/TRIV3/A2FPI7/A2FPI7-goa.tsv · publications/PMID_11897024.md

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

GO:0003677 DNA binding GO_MF
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot
Review rationale: The 129-residue target contains a KilA-N domain spanning residues 19–124 and a KilA/APSES helix-turn-helix assignment. The primary comparative analysis defining KilA-N identifies a conserved DNA-binding module in viral and cellular regulatory proteins (PMID:11897024). This provides a domain-based inference for broad DNA binding, not an experimental binding measurement on Trichomonas A2FPI7 or evidence for a specific DNA sequence. The molecular function is absent from the cached annotations.
Supporting Evidence:
  • file:TRIV3/A2FPI7/A2FPI7-uniprot.txt: "ID A2FPI7_TRIV3 Unreviewed; 129 AA. ... DR InterPro; IPR018004; KilA/APSES_HTH. ... DR InterPro; IPR017880; KilA_N. ... FT DOMAIN 19..124 ... FT /note="KilA-N""
  • PMID:11897024: "a novel, conserved DNA-binding domain (the KilA-N domain)"

Deep Research

Falcon

(A2FPI7-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(A2FPI7-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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