AKIP1

Summary: Binding to PRKACA, the PKA catalytic subunit - the interaction AKIP1 is named for. Modified to the specific catalytic-subunit term.

Reason: This is the defining interaction and the discovery paper maps it on both sides: AKIP1 binds the catalytic subunit's N-terminal A helix [PMID:15630084 "we identified a PKA-interacting protein (AKIP1) that binds to the amino terminus (residues 1-39) of the C subunit of PKA."], [PMID:15630084 "The interaction was localized to the A helix (residues 14-39) of the C subunit and to the carboxyl terminus of AKIP1."]. GO:0034236 protein kinase A catalytic subunit binding is the precise, verified child of GO:0051018 for this. Notably it is the catalytic subunit, not the RII regulatory subunit that AKAPs bind - AKIP1 is not an AKAP despite the name. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: protein kinase A catalytic subunit binding

Summary: Generic protein binding with FHL2, from HuRI, a proteome-scale binary interactome. Uninformative as a function statement; removed.

Reason: This row records an interaction with FHL2 scored in HuRI, a proteome-scale binary interactome [PMID:32296183 "Here we present a human 'all-by-all'"], a screen rather than a study of AKIP1, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Summary: Generic protein binding with GSN, from a neurodegenerative-disease yeast two-hybrid interactome. Uninformative as a function statement; removed.

Reason: This row records an interaction with GSN scored in a neurodegenerative-disease yeast two-hybrid interactome [PMID:32814053 "generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins"], a screen rather than a study of AKIP1, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Summary: Generic protein binding with FGFR3, from a neurodegenerative-disease yeast two-hybrid interactome. Uninformative as a function statement; removed.

Reason: This row records an interaction with FGFR3 scored in a neurodegenerative-disease yeast two-hybrid interactome [PMID:32814053 "generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins"], a screen rather than a study of AKIP1, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Summary: Generic protein binding with GW128, from a neurodegenerative-disease yeast two-hybrid interactome. Uninformative as a function statement; removed.

Reason: This row records an interaction with GW128 scored in a neurodegenerative-disease yeast two-hybrid interactome [PMID:32814053 "generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins"], a screen rather than a study of AKIP1, and nothing in it supports a more specific molecular function. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Summary: Binding to GRID2IP, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and GRID2IP is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to MPDZ, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and MPDZ is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to DLG4, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and DLG4 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to TJP1, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and TJP1 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to DLG1, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and DLG1 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to IL16, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and IL16 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to SCRIB, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and SCRIB is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to DLG2, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and DLG2 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to PDZK1, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and PDZK1 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to FRMPD2, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and FRMPD2 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to MAGI2, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and MAGI2 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to NHERF4, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and NHERF4 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to PATJ, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and PATJ is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to DLG3, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and DLG3 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to MAGI1, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and MAGI1 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to GRIP2, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and GRIP2 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to WHRN, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and WHRN is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Binding to GRIP1, a PDZ-domain protein, measured by PDZ-PBM affinity profiling. Modified to PDZ domain binding, which the assay itself measures.

Reason: The study is a systematic affinity screen of exactly this interaction class [PMID:36115835 "Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM)"], and GRIP1 is one of 18 PDZ-domain partners it reports for AKIP1. AKIP1 does carry a candidate motif: its C-terminal residues end F-P-V, a class II PDZ-binding motif (hydrophobic-x-hydrophobic at the carboxyl terminus). So 'PDZ domain binding' (GO:0030165) is what was measured and has a sequence basis. Two cautions travel with it: the AKIP1 values sit in the paper's supplementary data rather than its text, and these are peptide-domain affinities rather than interactions shown in cells. Per the project's GO:0005515 policy the generic term is not marked over-annotated - its defect is that it is uninformative - and removal is not a claim that the interaction is false.

Proposed replacements: PDZ domain binding

Summary: Nucleus from the UniProt subcellular-location vocabulary; matches direct observation of nuclear speckles.

Reason: Directly observed: [PMID:15630084 "In normal breast (Hs 578 Bst) and HeLa cells, AKIP1 is present in the nucleus as speckles."]. AKIP1 has a mapped nuclear localization signal, and its known function is nuclear - it raises nuclear PKA catalytic subunit [PMID:15630084 "Upon stimulation with forskolin, HeLa cells expressing AKIP1 accumulated higher levels of the endogenous C subunit in the nucleus."] and acts on the p65 transcription factor.

Summary: Nucleoplasm, inherited through the PANTHER node; consistent with direct observation.

Reason: Directly observed: [PMID:15630084 "In normal breast (Hs 578 Bst) and HeLa cells, AKIP1 is present in the nucleus as speckles."]. AKIP1 has a mapped nuclear localization signal, and its known function is nuclear - it raises nuclear PKA catalytic subunit [PMID:15630084 "Upon stimulation with forskolin, HeLa cells expressing AKIP1 accumulated higher levels of the endogenous C subunit in the nucleus."] and acts on the p65 transcription factor.

Summary: Nucleoplasm from Human Protein Atlas immunofluorescence; consistent with the original observation.

Reason: Directly observed: [PMID:15630084 "In normal breast (Hs 578 Bst) and HeLa cells, AKIP1 is present in the nucleus as speckles."]. AKIP1 has a mapped nuclear localization signal, and its known function is nuclear - it raises nuclear PKA catalytic subunit [PMID:15630084 "Upon stimulation with forskolin, HeLa cells expressing AKIP1 accumulated higher levels of the endogenous C subunit in the nucleus."] and acts on the p65 transcription factor.

Summary: Regulation of NON-canonical NF-kappaB signalling, from InterPro. AKIP1 acts on p65, the canonical pathway; modified to the canonical term.

Reason: The essence - AKIP1 regulates NF-kappaB - is well supported, but the branch is wrong. The mechanism is PKA phosphorylation of p65 on Ser-276 [PMID:20562110 "attenuated PKA-dependent phosphorylation of p65 on Ser-276"], which AKIP1 enables [PMID:20562110 "This inhibitory function of PKAc in NF-kappaB signaling was reversed by overexpression of AKIP1 in 293 cells."], and p65 is the canonical-pathway subunit; the non-canonical pathway runs through NIK, p100 processing and RelB. AKIP1 binds p65 itself, directly [PMID:18178962 "The interaction between AKIP1 and p65 was confirmed by glutathione S-transferase pull-down assay in vitro and immunoprecipitation-Western blotting assay in vivo."], with the kinase in the same complex [PMID:18178962 "We found that the PKAc was present in the AKIP1.p65 complex and enhanced the transcriptional activity of NF-kappaB by phosphorylating p65."]. Direction: the effect depends on the splice variant [PMID:23319652 "This regulation is dependent on the splice variants of AKIP1."] - [PMID:23319652 "AKIP1b was shown to recruit the histone deacetylase silent mating type information regulation 2 homolog (SIRT1) in a NEDDylation (NEDD8, neural precursor cell expressed, developmentally down-regulated 8-mediated)-dependent manner and repress transcription"], whereas [PMID:23319652 "In contrast, AKIP1a was shown to recruit NF-κB in a PKA-dependent manner and enhance transcription"]. The product annotated here is the canonical isoform, AKIP1a [file:genes/human/AKIP1/AKIP1-uniprot.txt "IsoId=Q9NQ31-1; Sequence=Displayed;"], which enhances, so the replacement is GO:0043123 positive regulation of canonical NF-kappaB signal transduction. The repression is restricted to AKIP1b, a different isoform, and would belong on an isoform-specific annotation rather than tempering this one.

Proposed replacements: positive regulation of canonical NF-kappaB signal transduction

Summary: AKIP1 binds both the PKA catalytic subunit and its substrate p65, and the kinase is found in the AKIP1-p65 complex - it brings kinase and substrate together. That is signaling adaptor activity.

Reason: Participation: AKIP1 makes both contacts itself. It binds the catalytic subunit's A helix [PMID:15630084 "we identified a PKA-interacting protein (AKIP1) that binds to the amino terminus (residues 1-39) of the C subunit of PKA."] and, independently, p65 [PMID:18178962 "we have identified protein kinase A-interacting protein 1 (AKIP1) as a binding partner of NF-kappaB p65 subunit, and AKIP1 enhances the NF-kappaB-mediated gene expression."], confirmed by pull-down and co-immunoprecipitation [PMID:18178962 "The interaction between AKIP1 and p65 was confirmed by glutathione S-transferase pull-down assay in vitro and immunoprecipitation-Western blotting assay in vivo."]; the kinase is present in that complex and phosphorylates p65 [PMID:18178962 "We found that the PKAc was present in the AKIP1.p65 complex and enhanced the transcriptional activity of NF-kappaB by phosphorylating p65."], and the effect is lost on knockdown [PMID:18178962 "When AKIP1 was knocked down by RNA interference, the PMA-mediated NF-kappaB-dependent gene expression was abolished, indicating a physiological role of AKIP1."]. GO:0035591 is the binding activity that brings components of one signalling pathway together so they act in a coordinated way, which is this. It is the same term the AKAP7 review uses for the analogous PKA-to-channel bridge; AKIP1 is not an AKAP, but it does the same kind of work with a different subunit. No IPI partner accession is recorded because the abstract does not state the species of the co-immunoprecipitation, and recording a guessed one would misstate what was tested.