TRAF2 is a cytoplasmic adaptor that organizes TNF receptor superfamily signaling complexes. Its C-terminal TRAF region engages receptors and associated proteins, while oligomerization and recruitment of cIAP ubiquitin ligases connect receptor activation to NF-kappaB, MAP kinase signaling and regulation of cell survival. TRAF2 also participates in selected immune-receptor and ER-stress signaling assemblies. Intrinsic ubiquitin-ligase activity has been reported in cofactor-dependent assays but remains mechanistically contested.
Summary: Intrinsic TRAF2 ubiquitin-transfer activity is contested at the mechanistic level: the RING/E2 structural and biochemical study finds an unfavorable E2 interface, whereas a later purified-protein study reports S1P-dependent RIP1 ubiquitination and excludes detectable cIAP1/2 contamination. The positive assay cannot be discarded from the negative study alone, nor can cIAP recruitment establish TRAF2 catalysis. A universal autonomous E3 assignment remains unresolved. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: Intrinsic TRAF2 ubiquitin-transfer activity is contested at the mechanistic level: the RING/E2 structural and biochemical study finds an unfavorable E2 interface, whereas a later purified-protein study reports S1P-dependent RIP1 ubiquitination and excludes detectable cIAP1/2 contamination. The positive assay cannot be discarded from the negative study alone, nor can cIAP recruitment establish TRAF2 catalysis. A universal autonomous E3 assignment remains unresolved. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.
In agreement with previous studies 20,21, incubation of purified RIP1 with recombinant TRAF2, ubiquitin, the ubiquitin-activating enzyme E1, and Ubc13/Uev1a, an E2 that facilitates Lys 63 polyubiquitination, failed to produce ubiquitinated RIP1. Remarkably however, addition of S1P induced efficient TRAF2-mediated ubiquitination of RIP1 (Fig. 3a).
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: Direct binding of recombinant human TRAF2 to the CD40 cytoplasmic tail and recruitment to TNF receptor signaling assemblies establish receptor binding and receptor-complex membership. This is intracellular receptor engagement, not binding to extracellular TNF cytokine. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: Direct binding of recombinant human TRAF2 to the CD40 cytoplasmic tail and recruitment to TNF receptor signaling assemblies establish receptor binding and receptor-complex membership. This is intracellular receptor engagement, not binding to extracellular TNF cytokine. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
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.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 is a cytoplasmic signaling adaptor recruited to the intracellular side of ligand-engaged receptors. Cytosolic and receptor-associated membrane pools are compatible, and no integral-membrane or extracellular localization is implied. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 is a cytoplasmic signaling adaptor recruited to the intracellular side of ligand-engaged receptors. Cytosolic and receptor-associated membrane pools are compatible, and no integral-membrane or extracellular localization is implied. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
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.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 is a cytoplasmic signaling adaptor recruited to the intracellular side of ligand-engaged receptors. Cytosolic and receptor-associated membrane pools are compatible, and no integral-membrane or extracellular localization is implied. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 is a cytoplasmic signaling adaptor recruited to the intracellular side of ligand-engaged receptors. Cytosolic and receptor-associated membrane pools are compatible, and no integral-membrane or extracellular localization is implied. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
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.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: The experimentally resolved RING/zinc-finger architecture supports structural metal coordination. This structural property is compatible with adaptor function and does not establish ubiquitin-ligase activity. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: The experimentally resolved RING/zinc-finger architecture supports structural metal coordination. This structural property is compatible with adaptor function and does not establish ubiquitin-ligase activity. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: TRAF2 coordinates TNF-family receptor signaling, activating NF-kappaB/JNK and controlling survival versus apoptosis through receptor-associated assemblies. This process participation is supported even when the ubiquitin chemistry is performed by recruited cIAPs. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,.
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.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: The experimentally resolved RING/zinc-finger architecture supports structural metal coordination. This structural property is compatible with adaptor function and does not establish ubiquitin-ligase activity. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: The experimentally resolved RING/zinc-finger architecture supports structural metal coordination. This structural property is compatible with adaptor function and does not establish ubiquitin-ligase activity. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: S1P-dependent recombinant TRAF2 autoubiquitination is reported, but TRAF2 is also a directly demonstrated cIAP substrate. A ubiquitinated TRAF2 band alone does not establish self-catalysis; the conflicting E2-interface evidence requires a cofactor- and preparation-specific interpretation. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: S1P-dependent recombinant TRAF2 autoubiquitination is reported, but TRAF2 is also a directly demonstrated cIAP substrate. A ubiquitinated TRAF2 band alone does not establish self-catalysis; the conflicting E2-interface evidence requires a cofactor- and preparation-specific interpretation. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.
Although c-IAP1 bound TRAF2 and TRAF1 in vitro, it ubiquitinated only TRAF2.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Summary: Intrinsic TRAF2 ubiquitin-transfer activity is contested at the mechanistic level: the RING/E2 structural and biochemical study finds an unfavorable E2 interface, whereas a later purified-protein study reports S1P-dependent RIP1 ubiquitination and excludes detectable cIAP1/2 contamination. The positive assay cannot be discarded from the negative study alone, nor can cIAP recruitment establish TRAF2 catalysis. A universal autonomous E3 assignment remains unresolved. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
Reason: Intrinsic TRAF2 ubiquitin-transfer activity is contested at the mechanistic level: the RING/E2 structural and biochemical study finds an unfavorable E2 interface, whereas a later purified-protein study reports S1P-dependent RIP1 ubiquitination and excludes detectable cIAP1/2 contamination. The positive assay cannot be discarded from the negative study alone, nor can cIAP recruitment establish TRAF2 catalysis. A universal autonomous E3 assignment remains unresolved. Transfer to F7BIV4 is supported by the retained RING/zinc-finger and C-terminal TRAF architecture, 92.0% paired identity and complete human-sequence coverage; horse-specific experimental confirmation is unavailable.
These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.
In agreement with previous studies 20,21, incubation of purified RIP1 with recombinant TRAF2, ubiquitin, the ubiquitin-activating enzyme E1, and Ubc13/Uev1a, an E2 that facilitates Lys 63 polyubiquitination, failed to produce ubiquitinated RIP1. Remarkably however, addition of S1P induced efficient TRAF2-mediated ubiquitination of RIP1 (Fig. 3a).
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
Core Functions
Assembles TNF-family receptor signaling machinery by recruiting cIAP ubiquitin ligases and other partners, coupling receptor engagement to NF-kappaB/JNK signaling and control of cell survival.
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.
TRAF2 is required for TNF-alpha-mediated activation of c-Jun N-terminal kinase (JNK), contributes to activation of NF-kappaB, and mediates anti-apoptotic signals,.
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md
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.
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.
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
GO:0002726 positive regulation of T cell cytokine productionGO_BP
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: 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.
Supporting Evidence:
PMID:15125833: "RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells."
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md: "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."
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: 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.
Supporting Evidence:
PMID:9718306: "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."
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md: "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."
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: 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.
Supporting Evidence:
PMID:20447407: "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."
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md: "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."
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: 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.
Supporting Evidence:
PMID:20447407: "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."
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md: "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."
GO:0002637 regulation of immunoglobulin productionGO_BP
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: 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.
Supporting Evidence:
PMID:17360936: "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."
PMID:9718306: "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."
file:HORSE/TRAF2/TRAF2-bioinformatics/RESULTS.md: "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."