PMID:23575685(https://pubmed.ncbi.nlm.nih.gov/23575685/), DOI 10.1038/ncomms2687, solves PEA15 bound to ERK2: “occupying two key docking sites of ERK2”. This supports a direct kinase-regulatory role, not intrinsic kinase activity. PMID:10442631(https://pubmed.ncbi.nlm.nih.gov/10442631/) reports “PED/PEA-15 co-precipitated with both FADD and FLICE.” and inhibition of death-receptor apoptotic signaling.
PMID:9670003(https://pubmed.ncbi.nlm.nih.gov/9670003/), DOI 10.1093/emboj/17.14.3858, is cached as abstract-only after publisher XML/HTML/PDF retrieval failed. It describes cloned human PEA15 transfection into L6 cells, with increased surface GLUT1 but inhibited insulin-stimulated glucose transport and GLUT4 surface recruitment. This establishes regulation of transport; it does not automatically establish the more general directed-movement process GO:0008643 or an intrinsic transporter activity. QuickGO definitions checked 2026-09-08 distinguish this from GO:0046325 negative regulation of glucose import.
Horse A0A9L0RWM8 contains all 130 human residues at 100% identity plus an N-terminal extension of 46 aa. The conserved core strongly supports mechanistic transfer, but the extension could affect localization or regulation and is not experimentally characterized. It is not evidence of a different enzyme or transporter fold. Horse UniProt is unreviewed; no horse-specific functional source was identified in the initial literature search, so human research is prioritized.
Deep research: just deep-research-falcon HORSE PEA15 --fallback perplexity-lite failed (falcon "Failed to authenticate"; perplexity-lite HTTP 401 insufficient quota). No deep-research file was created. Literature used: cached PMID:23575685 (full text), PMID:10442631, PMID:11702783 (newly cached, abstract), PMID:9670003, plus the human PEA15 falcon report (genes/human/PEA15/PEA15-deep-research-falcon.md) for orientation only.
Identity / gene model (new script PEA15-bioinformatics/compare_sequences_rereview.py, output RESULTS-rereview.md): A0A9L0RWM8 (176 aa, Ensembl ENSECAT00000100520) is an alternative TrEMBL gene model of horse PEA15 (gene ENSECAG00000019187). Human Q15121 Met1 maps to horse position 47; residues 47-176 are 130/130 identical to human. The model carries a predicted 46-aa N-terminal extension (MLPTATLEETVPGADSQRALFLYQPGRATAGPFCLLAPGCASERAF). A second horse model from the same Ensembl gene, F7AD02 (139 aa), has a different 9-aa extension (MLPTATLEV) sharing only the first 8 residues, consistent with alternative upstream 5' exon/ATG usage. Neither horse entry is reviewed and no 130-aa horse entry exists, so there is no reviewed canonical horse product. No domain, catalytic or binding residue is missing: DED (horse 49-127), NES (53-63), D74 (120), S104 (150), S116 (162) and the ERK D-site segment (167-175) are all conserved. Whether the extension is translated is unknown.
Evolutionary grounding: UniProt places A0A9L0RWM8 and F7AD02 in PANTHER PTHR48169:SF1 (ASTROCYTIC PHOSPHOPROTEIN PEA-15), the same subfamily as human Q15121, mouse Q62048 and rat Q5U318. PAINT node PANTHER:PTN008298780 propagates GO:1902042 (IBA, donors MGI:104799 and Q15121); PAINT did not propagate MAPK cascade or the human IDA for negative regulation of D-glucose import (GO:0046325), so no NEW glucose term is proposed. The family review interpro/panther/PTHR48169/PTHR48169-review.yaml agrees with SF1 placement (lists this accession as a SF1 representative); no disagreement.
Changes vs previous version:
- GO:0000165 MAPK cascade: ACCEPT -> MODIFY to GO:0070372 regulation of ERK1 and ERK2 cascade (PEA15 regulates ERK localization/activation state, it is not a relay kinase or cascade scaffold) PMID:11702783.
- GO:0042981 regulation of apoptotic process: ACCEPT -> MODIFY to GO:1902042 (more specific term already on the gene).
- GO:0005737 and GO:1902042: ACCEPT retained, reasons now cite PAINT/SF1 placement and the conserved NES/DED.
- NEW MF: GO:0140311 protein sequestering activity (ERK cytoplasmic anchoring) PMID:11702783 and GO:0035877 death effector domain binding (FADD/caspase-8) PMID:10442631. No NEW process terms.
- Core functions rewritten: (1) ERK sequestration -> regulation of ERK1/2 cascade; (2) DED binding -> negative regulation of death-receptor extrinsic apoptosis. GO:0019887 protein kinase regulator activity was replaced as the core MF by the more precise sequestering activity.
Relative: human PEA15 (Q15121), ortholog in the same PANTHER subfamily; genes/human/PEA15/PEA15-ai-review.yaml exists with all 21 GOA rows reviewed. Suggestion for that review (not edited here): its GO:0000165 ACCEPT could likewise be refined to GO:0070372. Relevant modules (PEA15 not currently a part): modules/erk_cascade.yaml, modules/death_receptor_apoptotic_signaling.yaml.