Review annotations to NF-kappaB signaling pathway (canonical and non-canonical)

[pgaudet]

It seems like some annotations contain upstream proteins that should be annotated to 'regulation of NF-kappaB signal transduction' and/or using the relation 'acts upstream of or within' for the NF-kappaB terms:

GO:0038061 'non-canonical NF-kappaB signal transduction' GO:0007249 'canonical NF-kappaB signal transduction'

Background: see images here: https://docs.google.com/document/d/1ukxL3vKfLbV4NAiGSeGg3EbpLKijfXXOr0npHeUYLI4/edit#heading=h.lkbwi265yjnj

GO:0038061 non-canonical NF-kappaB signal transduction (was: NIK/NF-kappaB signaling)
The process in which a signal is passed on to downstream components within the cell through the NIK-dependent processing and activation of NF-kappaB. Begins with activation of the NF-kappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-kappa B2 protein (p100) leading to p100 processing and release of an active NF-kappaB (p52). The non-canonical NF-kappaB signaling pathway is generally activated by ligands of the TNF receptor superfamily, including lymphotoxin beta (LTB), CD40, OX40, RANK, TWEAK and B cell-activating factor (BAFF). PMID:11239468 PMID:15140882 PMID:34659217

GO:0007249 canonical NF-kappaB signal transduction (was: I-kappaB kinase/NF-kappaB signaling) The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB, also known as the canonical NF-kappaB signaling cascade. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. The canonical NF-kappaB pathway is mainly stimulated by proinflammatory cytokines such as IL-1beta, tumor necrosis factor (TNF)-alpha, antigen ligands, and toll-like receptors (TLRs). PMID:12773372 PMID:34659217

[pgaudet]

• InterPro:IPR030312 Interleukin-1 receptor-associated kinase 1-binding protein 1 > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249
• InterPro:IPR033621 TRAF-interacting protein with FHA domain-containing protein > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249
• InterPro:IPR038753 NF-kappa-B inhibitor-like protein 1 > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249
• InterPro:IPR039669 TRAF family member-associated NF-kappa-B activator > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249
• InterPro:IPR042227 NF-kappa-B inhibitor-interacting Ras-like protein > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

[pgaudet]

Annotations are here: https://docs.google.com/spreadsheets/d/1xDQq-ccCfAYv-lQ_T1_S_dWQWCxf3jYhejhTPW6AAGA/edit#gid=0

[pgaudet]

assigned_by

AgBase | 5 ARUK-UCL | 20 BHF-UCL | 3 CAFA | 6 MGI | 103 RGD | 3 UniProt | 69 ZFIN | 13

[sramachand]

ZFIN done

[RLovering]

UCL done

[sarach06]

Dear Pascale, Thank you very much. I have checked these InterPro entries, they have the GO:0007249 term associated. Best regards, Sara

[pgaudet]

@gthayman single RDG annotation left, I made a suggestion in the spreadsheet https://docs.google.com/spreadsheets/d/1xDQq-ccCfAYv-lQ_T1_S_dWQWCxf3jYhejhTPW6AAGA/edit#gid=0

[gthayman]

Changed.

[ukemi]

MGI done

[hattrill]

@pgaudet I had a look at the InterPro2GO associations - I think that these would be better as regulatory terms:

• InterPro:IPR030312 Interleukin-1 receptor-associated kinase 1-binding protein 1 > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

Update InterPro:IPR030312 to GO:0043123 positive regulation of canonical NF-kappaB signal transduction

* InterPro:IPR033621 TRAF-interacting protein with FHA domain-containing protein > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

From https://www.embopress.org/doi/full/10.15252/embr.202152878 Looks like it could be associated with both: GO:0043123 positive regulation of canonical NF-kappaB signal transduction and GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction, but it is best characterised for its interaction with the canonical pathway there I would suggest:

Update InterPro:IPR033621 to GO:0043123 positive regulation of canonical NF-kappaB signal transduction

* InterPro:IPR038753 NF-kappa-B inhibitor-like protein 1 > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

Update InterPro:IPR038753 to GO:0043124 negative regulation of canonical NF-kappaB signal transduction

* InterPro:IPR039669 TRAF family member-associated NF-kappa-B activator > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

Based on https://www.uniprot.org/uniprotkb/Q92844/entry: Update InterPro:IPR039669 to GO:0043124 negative regulation of canonical NF-kappaB signal transduction

* InterPro:IPR042227 NF-kappa-B inhibitor-interacting Ras-like protein > GO:I-kappaB kinase/NF-kappaB signaling ; GO:0007249

Update InterPro:IPR042227 to GO:0043124 negative regulation of canonical NF-kappaB signal transduction

[pgaudet]

@sarach06 @blazaropinto Would you please review the InterPro annotations based on Helen's suggestions above?

[suzialeksander]

@Antonialock can you just check if the UniProt and CAFA are done?

[pgaudet]

@sarach06 @blazaropinto Would you please review the InterPro annotations based on Helen's suggestions above? https://github.com/geneontology/go-annotation/issues/4682#issuecomment-1759617557

[blazaropinto]

Hi Pascale and Helen,

Thank you so much for that. I updated these 5 terms. The changes will be available in the next InterPro release. Best, Beatriz

[suzialeksander]

@pgaudet there are still holes in the spreadsheet but comments indicate this review is done, or as done as it will get. Is there any further action?

[pgaudet]

Let's close, thanks.