id: F7BIV4
gene_symbol: TRAF2
taxon:
  id: NCBITaxon:9796
  label: Equus caballus
status: COMPLETE
description: TRAF2 receptor-adaptor and immune-regulatory predictions are supported by primary mammalian
  experiments and a conserved horse sequence.
source_documents:
- projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv
- projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz
- projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/TRAF2.json
references:
- id: PMID:15125833
  title: The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes.
  full_text_unavailable: true
  findings: []
- id: file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
  title: HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
  findings: []
- id: PMID:9718306
  title: 'CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40
    signaling through multiple TRAF binding sites and TRAF hetero-oligomerization.'
  full_text_unavailable: true
  findings: []
- id: PMID:20447407
  title: Asymmetric recruitment of cIAPs by TRAF2.
  full_text_unavailable: true
  findings: []
- id: PMID:17360936
  title: The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving
    B-cell growth and differentiation.
  full_text_unavailable: true
  findings: []
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0002726
    label: positive regulation of T cell cytokine production
  predicted_term_type: GO_BP
  review:
    assessment: COR
    confidence_score: 2
    summary: TRAF2 knockdown suppresses TCR-dependent interleukin-2 production in the primary mammalian
      study. The selected horse protein retains the full human adaptor architecture at 92.0% paired identity,
      supporting conserved positive control of T-cell cytokine production. This inference does not require
      TRAF2 itself to catalyze ubiquitin transfer. The supported annotation is absent from the frozen
      horse GOA; model training membership is unknown.
    supported_by:
    - reference_id: PMID:15125833
      supporting_text: "RNAi-mediated \nsilencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent\
        \ IKK \nactivation and interleukin-2 production in T cells."
    - &id001
      reference_id: file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
      supporting_text: The downloaded human Q12933 sequence (501 residues) and selected horse F7BIV4 sequence
        (516 residues) share 92.0% identity among 501 paired residues. Paired coverage is 100.0% of human
        and 97.1% of horse.
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0005174
    label: CD40 receptor binding
  predicted_term_type: GO_MF
  review:
    assessment: COR
    confidence_score: 2
    summary: Recombinant human TRAF2 directly binds the CD40 cytoplasmic domain. Full coverage of the
      characterized human sequence, including the C-terminal receptor-binding TRAF region, supports the
      same molecular interaction for horse F7BIV4. The supported annotation is absent from the frozen
      horse GOA; model training membership is unknown.
    supported_by:
    - &id003
      reference_id: PMID:9718306
      supporting_text: 'Recombinant

        human TRAF proteins overexpressed in insect cells were biochemically

        characterized and used to finely map TRAF binding regions in the human CD40

        cytoplasmic domain. TRAF1, TRAF2, TRAF3, and TRAF6, but not TRAF4 or TRAF5,

        bound directly to the CD40 cytoplasmic domain.'
    - *id001
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0000151
    label: ubiquitin ligase complex
  predicted_term_type: GO_CC
  review:
    assessment: COR
    confidence_score: 2
    summary: A reconstituted TRAF2–cIAP1 complex establishes recruitment of a genuine E3 ligase by TRAF2.
      The conserved horse scaffold supports membership in a ubiquitin ligase complex; this annotation
      does not assert autonomous catalytic activity of TRAF2. The supported annotation is absent from
      the frozen horse GOA; model training membership is unknown.
    supported_by:
    - &id002
      reference_id: PMID:20447407
      supporting_text: 'To fulfill

        this role, cIAPs must be recruited to the receptor complex by

        TNF-receptor-associated factor (TRAF) 2. In this study, we reconstituted the

        complex between baculoviral IAP repeat (BIR) 1 of cIAP1 and the coiled-coil

        region of TRAF2, solved the structure of BIR1 from cIAP1, and mapped key binding

        residues on each molecule using mutagenesis.'
    - *id001
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0002947
    label: tumor necrosis factor receptor superfamily complex
  predicted_term_type: GO_CC
  review:
    assessment: COR
    confidence_score: 2
    summary: TRAF2 is the receptor-associated adaptor that recruits cIAP1/2 into TNF receptor superfamily
      signaling assemblies. The conserved horse architecture supports complex membership independently
      of the disputed intrinsic E3 mechanism. The supported annotation is absent from the frozen horse
      GOA; model training membership is unknown.
    supported_by:
    - *id002
    - *id001
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0002637
    label: regulation of immunoglobulin production
  predicted_term_type: GO_BP
  review:
    assessment: COR
    confidence_score: 2
    summary: Mouse CD40 C-terminal-tail experiments support antibody isotype switching through an alternative
      TRAF2-binding site, and direct human TRAF2–CD40 binding establishes the molecular connection. Conserved
      full-length horse TRAF2 supports this broad humoral-regulatory role. This is a mammalian functional
      inference, not direct horse antibody-response measurement or proof of every isotype-specific effect.
      The supported annotation is absent from the frozen horse GOA; model training membership is unknown.
    supported_by:
    - reference_id: PMID:17360936
      supporting_text: 'Previously, we have shown

        signaling through the C-terminal tail of CD40 in the absence of canonical

        TRAF-binding sites is capable of signaling through an alternative TRAF2-binding

        site. Here, we demonstrate that B cells from mice harboring CD40 with only the

        C-terminal tail can activate both canonical and noncanonical NFkappaB signaling

        pathways. Moreover, while lacking germinal center formation, several hallmarks

        of humoral immune responses including clonal B-cell activation/expansion,

        antibody isotype switching, and affinity maturation remain normal.'
    - *id003
    - *id001