MESK2 (Misexpression suppressor of KSR 2, CG15669) is the single Drosophila member of the animal NDRG (N-myc downstream-regulated) family. Its products are cytoplasmic proteins built around an Ndr alpha/beta-hydrolase-fold domain. At the nucleophile-elbow position that carries the catalytic serine in active hydrolases, MESK2 has glycine, as human NDRG2 does, so it is expected to be a noncatalytic fold-retaining protein rather than an esterase or lipase. The gene encodes several isoforms that share the Ndr core and differ at their N- and C-terminal extensions. When misexpressed in the developing eye, MESK2 modulates RAS1/KSR-dependent photoreceptor signalling. Knockdown in glia reduces the rhythmicity of circadian locomotor behaviour. Insertion alleles are recessive lethal. Its molecular activity, binding partners and mechanism are unknown.
The preferred accession for this review is Q8T0V2. These relationships are manually assessed.
REFERENCE PROTEOME EQUIVALENT · Reviewed 2026-10-21
Reference proteome: UP000000803
Q8T0V2 is a cDNA-derived TrEMBL record (clones GH02495 and GH02835) that is not itself in the reference proteome. A4UZR7 is the UP000000803 record for MESK2 isoforms A/E/F and has an identical sequence. Both represent the same 447-residue MESK2 isoform. This is not the gene-centric canonical product, which is Q7KVN0 (isoform I, 485 aa, identical to Q9GU50).
Exact full-length sequence identity between Q8T0V2 and A4UZR7, retrieved from UniProt REST on 2026-10-21.
file:DROME/MESK2/MESK2-bioinformatics/RESULTS-rereview.md
Q8T0V2 == A4UZR7 (sequence identical): True
A4UZR7 is a member of the D. melanogaster reference proteome; Q8T0V2 is not.
file:DROME/MESK2/MESK2-bioinformatics/RESULTS-rereview.md
A4UZR7 proteomes: UP000000803: Chromosome 2R
file:DROME/MESK2/MESK2-bioinformatics/RESULTS-rereview.md
Q8T0V2 proteomes: none
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Download this section (compressed HTML)Q: Is the HDA serine hydrolase activity annotation on the canonical MESK2 record (Q7KVN0, from PMID:33827210) supported by probe-dependent, inhibitor-competable labelling of MESK2 peptides, given that MESK2 has glycine at the catalytic-serine position?
Q: Do the MESK2 isoforms that differ at their N- and C-terminal extensions (isoforms A/E/F versus isoform I) have different interaction partners or subcellular distributions?
Q: Does MESK2 act in glia through the same molecular interactions that let its overexpression modulate RAS1/KSR signalling in the eye?
Experiment: Immunoprecipitation or proximity labelling of endogenously tagged MESK2 isoforms in adult glia and eye discs, to identify direct binding partners.
Type: proteomics
Experiment: Express recombinant MESK2 Ndr domain and test FP-probe labelling and esterase activity, with an engineered G234S variant as a positive-control comparison.
Type: biochemistry
Experiment: Glia-specific rescue of the MESK2 RNAi circadian phenotype with RNAi-resistant isoform A and isoform I transgenes.
Type: genetics
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular activity of MESK2 is unknown. No binding partner, ligand or regulated target has been identified, so the mechanism behind its Ras-modulating and glial circadian phenotypes cannot be stated.
BIOLOGY
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