PTN000391706 not GO:0046579 | positive regulation of Ras protein signal transduction

[ValWood]

• PTHR ID & PTN node:

GO:0046579 | positive regulation of Ras protein signal transduction | IBA with PTN000391706 , P49842 | GO_REF:0000033

• Sequences with problematic annotation (ID + gene/protein name):

ALL

• Type of Issue: Erroneous source or erroneous propagation, or other issue

Erroneous annotation:

These is a paper in Cell in 2019]
https://pubmed.ncbi.nlm.nih.gov/30712867/

This paper was quickly contested and has major issues with the sequence isoform (the mutant used is in an exon that is not part of the protein)

There was quickly a follow up paper
https://www.uniprot.org/citations/32531245
Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver.
which looks robust.
This was contested by the original authors
https://www.uniprot.org/citations/32531246
but their do seem to be major problems with the original paper.

More recently there have been a ruck of papers describing the actual role in transcription coupled repair
(note that it also does not seem to be a kinase, and it doesn't look like one)

STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair.
PMID: 39547229

Unlocking transcription-coupled DNA repair with the STK19 key.
Kuper J, Kisker C, Van Houten B.
Mol Cell. 2024 Dec 19;84(24):4693-4695. doi: 10.1016/j.molcel.2024.11.027.
PMID: 39706162

STK19 positions TFIIH for cell-free transcription-coupled DNA repair.
Mevissen TET, Kümmecke M, Schmid EW, Farnung L, Walter JC.
Cell. 2024 Dec 12;187(25):7091-7106.e24. doi: 10.1016/j.cell.2024.10.020. Epub 2024 Nov 14.
PMID: 39547228

STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.
Ramadhin AR, Lee SH, Zhou D, Salmazo A, Gonzalo-Hansen C, van Sluis M, Blom CMA, Janssens RC, Raams A, Dekkers D, Bezstarosti K, Slade D, Vermeulen W, Pines A, Demmers JAA, Bernecky C, Sixma TK, Marteijn JA.
Mol Cell. 2024 Dec 19;84(24):4740-4757.e12. doi: 10.1016/j.molcel.2024.10.030. Epub 2024 Nov 14.
PMID: 39547223

STK19 is a transcription-coupled repair factor that participates in UVSSA ubiquitination and TFIIH loading.
Tan Y, Gao M, Huang Y, Zhan D, Wu S, An J, Zhang X, Hu J.
Nucleic Acids Res. 2024 Nov 27;52(21):12767-12783. doi: 10.1093/nar/gkae787.
PMID: 39353615

Mutations found in cancer patients compromise DNA binding of the winged helix protein STK19.
Li J, Ma X, Wang X, Hu X, Fang S, Jin G, Liu K, Dong Z.
Sci Rep. 2024 Jun 18;14(1):14098. doi: 10.1038/s41598-024-64840-9.
PMID: 38890355

STK19 is a DNA/RNA-binding protein critical for DNA damage repair and cell proliferation.
Li Y, Gong Y, Zhou Y, Xiao Y, Huang W, Zhou Q, Tu Y, Zhao Y, Zhang S, Dai L, Sun Q.
J Cell Biol. 2024 Feb 5;223(2):e202301090. doi: 10.1083/jcb.202301090. Epub 2024 Jan 22.
PMID: 38252411

so the UniProt entry seems out of date.

• Add the label 'high priority' if needed. Generally high priority issues affect a lot of proteins, and annotations are incorrect (as opposed to just imprecise).

[ValWood]

note also that the name at HGNC has updated to
WHR1
winged helix repair factor 1
https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11398

[ValWood]

InterPro said "Thank you very much for this. We have been recently contacted from someone
from UniProt with this information as well" so no the new annotation is probably already there...