Probable PAINT IRD errors: draft report

Probable PAINT IRD errors: draft report

Draft for the PANTHER/PAINT curators, generated by paint_report.py. It has not been
sent. Each case links the review that argues it, with verbatim quotes in that file.

1. Family reviews: losses judged contradicted or too broad (14)

Family Node Blocked term Code Verdict Why (from the review) Suggested Review
PTHR10196 PTN000023394 GO:0005829 cytosol IRD LOSS_CONTRADICTED PTN000023394 is the eukaryotic glycerol kinase node (189 leaves: GK/Gk, GK2, GK3P, GK5, Gykl1, Drosophila Gk1/Gk2, yeast GUT1, Arabidopsis GLPK and other plant, fungal and protist glycerol kinases). On the same date (2024-11-19) PAINT placed a mitochondrion IBD on this node and an IRD blocking the cytosol IBD carried by the parent node PTN000023392. Retract the IRD interpro/panther/PTHR10196/PTHR10196-review.yaml
PTHR10638 PTN000067358 GO:0008131 primary methylamine oxidase activity IRD LOSS_CONTRADICTED This IRD NOT sits on the eutherian AOC3 clade (21 leaves; human, mouse and rat AOC3 and their orthologues in PTHR10638:SF23 MEMBRANE PRIMARY AMINE OXIDASE, plus a few unnamed great-ape SF94 sequences) and blocks the GO:0008131 IBD placed at PTN000067313. AOC3 is VAP-1, the semicarbazide-sensitive amine oxidase (SSAO), one of the best-characterised copper amine oxidases. Retract the IRD interpro/panther/PTHR10638/PTHR10638-review.yaml
PTHR10648 PTN000068762 GO:0005829 cytosol IRD LOSS_CONTRADICTED PTN000068762 is a single leaf, Arabidopsis PP2AA3 (Q38951, AT1G13320, SF36). The IRD blocks the cytosol IBD on the eukaryotic PP2A scaffold-subunit node PTN000068663, and both rows carry the same date (2025-09-02). Retract the IRD interpro/panther/PTHR10648/PTHR10648-review.yaml
PTHR11588 PTN000172659 GO:0005874 microtubule IRD LOSS_CONTRADICTED This IRD stops the tubulin-root IBD for microtubule (PTN000172598, seeded by alpha and beta tubulins) from descending into the gamma-tubulin clade (134 leaves; subfamilies SF7, SF62, SF79, SF381). The curator's intent is clear and biologically right in one sense: gamma-tubulin is not a lattice-forming tubulin, and the node instead carries IBDs for gamma-tubulin complex, spindle pole and microtubule nucleator activity. Retract the IRD interpro/panther/PTHR11588/PTHR11588-review.yaml
PTHR11588 PTN000172725 GO:0005737 cytoplasm IRD LOSS_CONTRADICTED This IRD stops the tubulin-root IBD for cytoplasm (PTN000172598) from descending into the Viridiplantae gamma-tubulin clade (62 leaves, all in SF7 TUBULIN GAMMA CHAIN, including Arabidopsis TUBG1 and TUBG2). Animal and fungal gamma-tubulins still inherit the term. Retract the IRD interpro/panther/PTHR11588/PTHR11588-review.yaml
PTHR11610 PTN000176957 GO:0005576 extracellular region IRD LOSS_CONTRADICTED PTN000176957 is the therian PNLIPRP1 orthogroup (nine leaves, all SF108). On 2026-05-28 PAINT placed IRDs here on lipase activity, extracellular region and lipid catabolic process, all overriding PTN008325466. Retract the IRD interpro/panther/PTHR11610/PTHR11610-review.yaml
PTHR11972 PTN001379754 GO:0000293 ferric-chelate reductase activity IRD LOSS_CONTRADICTED The IRD node is a single leaf, Arabidopsis FRO6 (Q8RWS6, At5g49730, subfamily SF69), and it blocks the ferric-chelate reductase IBD placed at the embryophyte node PTN000944413, whose seeds include the tandem paralog FRO7 (At5g49740). FRO6 and FRO7 are 87% identical and differ only in their N termini (FRO7 carries the stronger plastid transit peptide), so a sequence-level loss of catalysis in FRO6 alone is not expected. Retract the IRD interpro/panther/PTHR11972/PTHR11972-review.yaml
PTHR11972 PTN002279285 GO:0016175 superoxide-generating NAD(P)H oxidase activity IRD LOSS_TOO_BROAD In the upstream PANTHER IBD.gaf, the ancestral GO:0016175 IBD at PTN000239644 (dated 20230405) has a single seed, SGD:S000003128, which is S. cerevisiae AIM14/YNO1 (P53109). The IRD at PTN002279285 has the same date and covers a 42-leaf Dikarya clade of FRE-like proteins that contains AIM14 itself (leaf PTN000944297). Move the IRD to a lower node interpro/panther/PTHR11972/PTHR11972-review.yaml
PTHR19375 PTN001065099 GO:0042026 protein refolding IRD LOSS_TOO_BROAD PTN001065099 is not the ribosome-associated branch alone. Its 57 members span all of the fungal cytosolic Hsp70 subfamilies: the SSA chaperones (SF395 with S. cerevisiae SSA1/SSA2, S. pombe ssa1/ssa2, Neurospora hsps-1; SF385 with SSA3/SSA4), the ribosome-associated SSB group (SF467: SSB1/SSB2, S. pombe sks2), the RAC subunit SSZ1 (SF539) and a small LHS1-like group (SF522). Move the IRD to a lower node interpro/panther/PTHR19375/PTHR19375-review.yaml
PTHR24056 PTN000756102 GO:0004674 protein serine/threonine kinase activity IRD LOSS_CONTRADICTED PTN000756102 is the CDKL5 clade (40 leaves, almost all PTHR24056:SF111, plus the zebrafish/medaka SF547 copies): vertebrate CDKL5, amphioxus, sea urchin, Monosiga, budding yeast YGK3, Giardia, Paramecium, Phytophthora, Chlamydomonas and Klebsormidium sequences. The IRD blocks the deep GO:0004674 IBD at PTN000623091 from descending, while the same node keeps an IBA for the parent GO:0004672 protein kinase activity from PTN000623091. Retract the IRD interpro/panther/PTHR24056/PTHR24056-review.yaml
PTHR24056 PTN000623095 GO:0016592 mediator complex IRD LOSS_CONTRADICTED PTN000623095 is the bilaterian CDK8/CDK19 clade (60 leaves): vertebrate CDK8 (SF243) and CDK19 (SF570), plus invertebrate Cdk8 (SF495, e.g. Drosophila Cdk8 and C. elegans cdk-8) and nematode dyf-18 (SF469). Retract the IRD interpro/panther/PTHR24056/PTHR24056-review.yaml
PTHR42884 PTN001647685 GO:0005802 trans-Golgi network IRD LOSS_CONTRADICTED PTN001647685 is the PC1/3 (PCSK1) orthogroup (29 leaves, all SF14). PAINT placed the TGN IBD on the opisthokont node PTN000082856 on 2024-11-21, seeded by furin (mouse MGI:97513, human P09958), yeast KEX2 (SGD:S000005182), rat Pcsk5 (RGD:620326) and rat Pcsk1 (RGD:3272). Retract the IRD interpro/panther/PTHR42884/PTHR42884-review.yaml
PTHR45618 PTN000642212 GO:0017077 oxidative phosphorylation uncoupler activity IRD LOSS_CONTRADICTED This IRD NOT covers the mammalian UCP3 clade (15 leaves, all in PTHR45618:SF2 MITOCHONDRIAL TRANSPORTER UCP3-RELATED, including human, mouse and rat UCP3) and blocks the GO:0017077 IBD at PTN000642156 that PAINT seeded from MGI:98894, RGD:3931 and Arabidopsis AT3G54110. GO:0017077 is defined as proton transfer into the matrix that dissipates the gradient (proton leak); it does not require thermogenesis. Retract the IRD interpro/panther/PTHR45618/PTHR45618-review.yaml
PTHR45807 PTN002910252 GO:0007259 cell surface receptor signaling pathway via JAK-STAT IRD LOSS_CONTRADICTED This row is a negated IRD (dated 2026-08-28, the same day the Bilateria GO:0007259 IBD was refreshed). It asserts that the euteleostome TYK2 clade (SF6) has diverged so far that it no longer takes part in receptor JAK-STAT signaling, and its effect is that human and mouse TYK2 get no GO:0007259 IBA (confirmed in QuickGO). Retract the IRD interpro/panther/PTHR45807/PTHR45807-review.yaml

2. Gene reviews: losses judged contradicted or too broad (4)

From propagation_review.paint_losses in the gene reviews, for losses no family
review has assessed. The quoted evidence is in each gene review.

Family Node Blocked term Code Clade (leaves) Judged Gene (row) Why (from the review) Suggested Review
PTHR13194 PTN000995776 GO:0010257 NADH dehydrogenase complex assembly IRD 11 CONTRADICTED cia30 (IBA:ACCEPT) N. crassa cia30 disruption mutants accumulate the matrix arm and the small membrane-arm intermediate but cannot form the large membrane-arm assembly intermediate of complex I (PMID:9769214). The IRD clade is fungal CIA30/NDUFAF1 (11 proteins, including N. crassa cia30) and includes complex I-containing fungi. Retract the IRD, or restrict it to a branch that has lost complex I. genes/NEUCR/cia30/cia30-ai-review.yaml
PTHR10454 PTN000047958 GO:0031265 CD95 death-inducing signaling complex IRD 6 CONTRADICTED CFLAR (IBA:ACCEPT) The CD95/TRAILR-FADD DISC assembles with procaspase-8 and cFLIP (PMID:38710704). The IRD clade is mammalian CFLAR (6 proteins). The other CFLAR IRDs on this node (endopeptidase activity, macrophage differentiation, neuron apoptosis) agree with the gene review. Retract the IRD for GO:0031265 only. genes/human/CFLAR/CFLAR-ai-review.yaml
PTHR12929 PTN000309189 GO:0032217 riboflavin transmembrane transporter activity IRD 4 CONTRADICTED SLC52A1 (IBA:ACCEPT) Human SLC52A1 (RFVT1) transports riboflavin in direct assays (IDA, PMID:20463145 and PMID:21854757). The IRD node is the primate SLC52A1 clade (4 proteins), and it blocks both GO:0032217 riboflavin transmembrane transporter activity and GO:0032218 riboflavin transport. Retract the IRD for GO:0032217 and GO:0032218. genes/human/SLC52A1/SLC52A1-ai-review.yaml
PTHR12929 PTN000309189 GO:0032218 riboflavin transport IRD 4 CONTRADICTED SLC52A1 (IBA:ACCEPT) Human SLC52A1 (RFVT1) transports riboflavin in direct assays (IDA, PMID:20463145 and PMID:21854757). The IRD node is the primate SLC52A1 clade (4 proteins), and it blocks both GO:0032217 riboflavin transmembrane transporter activity and GO:0032218 riboflavin transport. Retract the IRD for GO:0032217 and GO:0032218. genes/human/SLC52A1/SLC52A1-ai-review.yaml

3. Stale overrides: the blocked IBD is gone (14)

The IRD's ancestral node no longer carries an IBD for the term, so the IRD blocks
nothing and could be removed. Source: PAINT IBD.gaf via fetch_paint_ird.py.

Family IRD node Term Ancestral node IRD date
PTHR11802 PTN001720128 GO:0005773 vacuole PTN001720040 20210904
PTHR12260 PTN000262554 GO:0005634 nucleus PTN000262496 20240305
PTHR12897 PTN000984912 GO:0005765 lysosomal membrane PTN000307264 20240306
PTHR12919 PTN002293408 GO:0032543 mitochondrial translation PTN000308745 20240306
PTHR13681 PTN002299200 GO:0000381 regulation of alternative mRNA splicing, via spliceosome PTN001784834 20250826
PTHR24261 PTN001546628 GO:0031012 extracellular matrix PTN002799862 20250903
PTHR33269 PTN002115829 GO:0045271 respiratory chain complex I PTN004990314 20240801
PTHR43048 PTN000482983 GO:0005739 mitochondrion PTN001468099 20241121
PTHR43782 PTN002886720 GO:0005634 nucleus PTN000144387 20200401
PTHR43795 PTN008453022 GO:0009507 chloroplast PTN008453015 20260710
PTHR45639 PTN009180209 GO:0030968 endoplasmic reticulum unfolded protein response PTN000452651 20260224
PTHR45688 PTN000241152 GO:0005739 mitochondrion PTN000241036 20240229
PTHR45688 PTN000241488 GO:0005739 mitochondrion PTN000241036 20240229
PTHR46590 PTN008709838 GO:0005739 mitochondrion PTN008709837 20250904

4. Fully re-annotated: the IRD blocks nothing (20)

Every protein in the clade still gets a more specific term (is_a or part_of below the
blocked one) as a positive IBA, from the IRD node itself or an ancestor. The IRD then
contradicts PAINT's own propagation: it should also block that term, or be retracted.
Source: ird_seed_check.py (see ird_seed_check.md).

Family IRD node Blocked term IRD date Clade (checked/all) Kind IBA sources (node, term, where)
PTHR10131 PTN007421972 GO:0007166 cell surface receptor signaling pathway 20250411 3/3 above PTN000805720 GO:0033209 (above)
PTHR10794 PTN000082718 GO:0034338 short-chain carboxylesterase activity 20200313 1/1 above PTN000082647 GO:0008126 (above)
PTHR11119 PTN002476593 GO:0015882 L-ascorbic acid transmembrane transport 20241120 1/1 above PTN002595861 GO:0015229 (above)
PTHR11610 PTN000176957 GO:0016042 lipid catabolic process 20241120 9/9 above PTN000906454 GO:0019433 (above)
PTHR11610 PTN000176957 GO:0016298 lipase activity 20260528 9/9 above PTN000906454 GO:0004465 (above); PTN000906454 GO:0008970 (above)
PTHR11610 PTN008325477 GO:0016042 lipid catabolic process 20241120 12/12 above PTN000906454 GO:0019433 (above)
PTHR11610 PTN008325477 GO:0016298 lipase activity 20260528 12/12 above PTN000906454 GO:0004465 (above); PTN000906454 GO:0008970 (above)
PTHR11958 PTN002632768 GO:0015813 L-glutamate transmembrane transport 20250903 20/20 above PTN000238242 GO:0005313 (above)
PTHR19321 PTN004511774 GO:0005819 spindle 20230603 1/1 above PTN000448590 GO:1990023 (above)
PTHR24056 PTN000623365 GO:0000307 cyclin-dependent protein kinase holoenzyme complex 20260313 1/1 above PTN000623095 GO:1990508 (above)
PTHR24221 PTN000657226 GO:0055085 transmembrane transport 20250903 10/10 above PTN000657189 GO:0042626 (above)
PTHR24221 PTN000657241 GO:0055085 transmembrane transport 20250903 12/12 same node PTN000657189 GO:0042626 (above); PTN000657241 GO:0042910 (same node)
PTHR24221 PTN000657258 GO:0055085 transmembrane transport 20250903 1/1 above PTN000657189 GO:0042626 (above)
PTHR24221 PTN000657261 GO:0055085 transmembrane transport 20250903 1/1 above PTN000657189 GO:0042626 (above)
PTHR24221 PTN001542468 GO:0055085 transmembrane transport 20250903 3/3 above PTN000657189 GO:0042626 (above)
PTHR24235 PTN000662954 GO:0007218 neuropeptide signaling pathway 20250618 8/8 above PTN002538187 GO:0008188 (above)
PTHR33694 PTN008658623 GO:0005737 cytoplasm 20260828 54/54 same node PTN008658623 GO:0005739 (same node)
PTHR43020 PTN000228777 GO:0035596 methylthiotransferase activity 20260530 85/85 above PTN000228824 GO:0035597 (above)
PTHR43020 PTN000228777 GO:0035600 tRNA methylthiolation 20241121 85/85 above PTN000228824 GO:0035597 (above)
PTHR48017 PTN004585555 GO:0003333 amino acid transmembrane transport 20260828 31/31 above PTN001118955 GO:0015171 (above)