id: A0A9L0JBM7
gene_symbol: HOXA2
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: Assessment of 3 ProtNLM2 GO predictions for donkey HOXA2 (A0A9L0JBM7). All three terms
  (DNA binding, DNA-binding transcription factor activity RNA polymerase II-specific, nucleus) are already
  in donkey GOA and are biologically supported by transfer from experimentally characterised mouse and
  human HOXA2, which share PANTHER subfamily PTHR45664:SF3 with the donkey protein, whose homeodomain
  is identical to human. The TF activity and nucleus terms are correct but not novel (CNN). DNA binding
  is correct but less specific than RNA polymerase II cis-regulatory region sequence-specific DNA binding
  (GO:0000978), which the donkey gene already carries and its gene review accepts (LSP). No non-GO
  ProtNLM2 outputs (function text or location) were emitted for this accession.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- genes/EQUAS/HOXA2/HOXA2-goa.tsv
- genes/EQUAS/HOXA2/HOXA2-bioinformatics/O43364-uniprot.txt
- genes/EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
- genes/EQUAS/HOXA2/HOXA2-bioinformatics/RESULTS.md
- genes/EQUAS/HOXA2/HOXA2-ai-review.yaml
- genes/EQUAS/HOXA2/HOXA2-uniprot.txt
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0003677
    label: DNA binding
  predicted_term_type: GO_MF
  review:
    assessment: LSP
    confidence_score: 2
    summary: HOXA2 binds DNA through its homeodomain, which is 100% identical between donkey and human,
      so the prediction is correct. Donkey GOA already contains DNA binding and, more specifically, RNA
      polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) and sequence-specific
      double-stranded DNA binding (GO:1990837), both grounded in ortholog experiments. Because a supported,
      more specific annotation exists (GO:0000978 is a descendant of GO:0003677 and is accepted in the gene
      review, which marks DNA binding as too general), the prediction is less precise.
    supported_by:
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P31245 Hoxa2 enables GO:0000978 "RNA polymerase II cis-regulatory region sequence-specific
        DNA binding" IDA PMID:15634706
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: O43364 HOXA2 enables GO:1990837 "sequence-specific double-stranded DNA binding"
        IDA PMID:28473536
    - reference_id: PMID:15634706
      supporting_text: Hoxa2 binds to this promoter region.
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/RESULTS.md
      supporting_text: 'human region 143-202: 60 of 60 residues aligned, 60 identical'
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  predicted_term_type: GO_MF
  review:
    assessment: CNN
    confidence_score: 2
    summary: HOXA2 is a sequence-specific homeodomain transcription factor; mouse Hoxa2 has IDA support
      for repressing and activating RNA polymerase II targets. The exact term is already in donkey GOA
      (combined IEA) and is the core function accepted by the gene review; the donkey protein shares PANTHER
      subfamily PTHR45664:SF3 and an identical homeodomain with the characterised orthologs. Correct but not novel; the repressor child term GO:0001227 is also present in GOA,
      but HOXA2 also activates targets, so the general TF term is appropriate rather than less precise.
    supported_by:
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/O43364-uniprot.txt
      supporting_text: Sequence-specific transcription factor which is part of a
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P31245 Hoxa2 enables GO:0001227 "DNA-binding transcription repressor activity,
        RNA polymerase II-specific" IDA PMID:15634706
    - reference_id: PMID:15634706
      supporting_text: These results strongly suggest that Six2 is a direct target of Hoxa2.
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P31245 Hoxa2 acts_upstream_of_or_within GO:0045944 "positive regulation of transcription
        by RNA polymerase II" IDA PMID:18787068
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/RESULTS.md
      supporting_text: 'human region 143-202: 60 of 60 residues aligned, 60 identical'
    - reference_id: file:EQUAS/HOXA2/HOXA2-uniprot.txt
      supporting_text: PTHR45664:SF3; HOMEOBOX PROTEIN HOX-A2
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0005634
    label: nucleus
  predicted_term_type: GO_CC
  review:
    assessment: CNN
    confidence_score: 2
    summary: Nuclear localization is experimentally shown for mouse Hoxa2 (immunodetection in embryonic
      neural tube nuclei), and its regulated exit from the nucleus via the KPC2 interactor implies a nuclear
      steady state; human HOXA2 is curated as nuclear. The donkey protein is in the same PANTHER subfamily
      (PTHR45664:SF3) with an identical homeodomain, so the transfer is justified. The exact term is already
      in donkey GOA and is accepted as a core location by the gene review. Correct but not novel.
    supported_by:
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P31245 Hoxa2 located_in GO:0005634 "nucleus" IDA PMID:10536059
    - reference_id: PMID:10536059
      supporting_text: Hoxa-2 in nuclei of cells in this region.
    - reference_id: PMID:26303204
      supporting_text: KPC2 diminishes the transcriptional activity and induces the nuclear exit of Hoxa2.
    - reference_id: file:EQUAS/HOXA2/HOXA2-bioinformatics/O43364-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
references:
- id: PMID:15634706
  title: Hoxa2 downregulates Six2 in the neural crest-derived mesenchyme.
  findings: []
- id: PMID:10536059
  title: Differential expression of Hoxa-2 protein along the dorsal-ventral axis of the developing and adult mouse spinal cord.
  findings: []
- id: PMID:26303204
  title: KPC2 relocalizes HOXA2 to the cytoplasm and decreases its transcriptional activity.
  findings: []
- id: file:EQUAS/HOXA2/HOXA2-uniprot.txt
  title: UniProt record for donkey HOXA2 (A0A9L0JBM7)
  findings: []
- id: file:EQUAS/HOXA2/HOXA2-bioinformatics/O43364-uniprot.txt
  title: UniProt record for human HOXA2 (O43364)
  findings: []
- id: file:EQUAS/HOXA2/HOXA2-bioinformatics/ortholog_experimental_goa.txt
  title: Experimental GO annotations of human and mouse HOXA2 orthologs (QuickGO)
  findings: []
- id: file:EQUAS/HOXA2/HOXA2-bioinformatics/RESULTS.md
  title: 'HOXA2: donkey-human sequence comparison'
  findings: []