CG3515 encodes a 395-residue WD40-repeat protein of the Swd2/WDR82 family (PANTHER PTHR19861:SF0), the family whose members are non-catalytic subunits of Set1/COMPASS H3K4 methyltransferase complexes and, in yeast, also act in RNA polymerase II transcription termination. It is a rapidly diverging Drosophila paralog of the conserved fly WDR82 ortholog Wdr82 (CG17293), sharing only about 35% identity with either fly Wdr82 or human WDR82, and it carries a C-terminal extension absent from those proteins. Its expression is strongly testis-biased. By phylogenetic inference it is a nuclear, chromatin-associated Set1/COMPASS-type subunit, but it has not been studied directly. The fly Set1/COMPASS complex purified from S2 cells contains Wdr82, not CG3515, so whether CG3515 forms a testis-specific variant complex, or has another role, is unknown.
Summary: Phylogenetic inference from the Swd2/WDR82 node; CG3515 lies inside PTHR19861:SF0 with fly Wdr82 and human WDR82, whose chromatin association is experimentally established.
Reason: The PAINT node PTN000458398 covers the Swd2/WDR82 subfamily, and CG3515 is a member of PTHR19861:SF0 together with fly Wdr82 (Q9VLN1) and human WDR82 (Q6UXN9). Mammalian WDR82 associates with chromatin in an H2B ubiquitination-dependent manner (PMID:18838538), and the same behaviour is described for the yeast and human proteins in the fly COMPASS study (PMID:21875999). CG3515 is a strongly diverged paralog (about 35% identity to Wdr82/WDR82, versus 69% between fly Wdr82 and human WDR82), which lowers confidence that every family property is retained. However, there is no CG3515-specific evidence of loss, and chromatin binding is the broad, family-level property PAINT chose to propagate, so the inference is accepted as the best current statement. It is not a direct CG3515 assay.
Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes.
file:DROME/CG3515/CG3515-uniprot.txt
DR PANTHER; PTHR19861:SF0; WD REPEAT-CONTAINING PROTEIN 82; 1.
Summary: Nuclear localization is consistent with membership of the Swd2/WDR82 subfamily, whose characterized members are nuclear chromatin-complex subunits.
Reason: The IEA itself derives from an ARBA rule, which is not independent support. It is accepted because nuclear localization follows from the family placement (PTHR19861:SF0, InterPro IPR037867 Swd2/WDR82) and the chromatin/COMPASS biology of characterized members; the fly Set1 complex was purified from nuclear extracts using tagged Wdr82 (PMID:21875999). No CG3515 localization assay exists.
Summary: Broad ARBA process assignment with no CG3515-specific basis; the RNA-processing role of the family is a yeast CPF-associated function that PAINT did not propagate to this node.
Reason: This row comes from an ARBA machine-learning rule and is very broad. The RNA-related role in the family is the yeast Swd2 function in CPF-associated transcription termination and snoRNA/mRNA 3' end formation (PMID:15024081, PMID:15146080). PAINT propagated chromatin binding and Set1C/COMPASS membership from the Swd2/WDR82 node but no RNA-processing term, which should be read as a deliberate decision. Transcription regulation through COMPASS would formally fall under RNA metabolism, but that would be a downstream consequence of a chromatin complex, not participation in RNA metabolic chemistry, and CG3515 has no RNA-related evidence of its own. The term is not demonstrably false, so it is marked as an over-annotation rather than removed.
Swd2, an essential WD repeat protein in Saccharomyces cerevisiae, is a component of two very different complexes: the cleavage and polyadenylation factor CPF and the Set1 methylase, which modifies lysine 4 of histone H3 (H3-K4).
Summary: Phylogenetic inference from the Swd2/WDR82 node, seeded by experimentally characterized COMPASS subunits including fly Wdr82; CG3515 itself was not detected in fly Set1 complex purifications from S2 cells.
Reason: Set1C/COMPASS membership is the defining, deeply conserved property of the Swd2/WDR82 subfamily (yeast Swd2, S. pombe Swd2, human WDR82, fly Wdr82, Dictyostelium donors). CG3515 sits inside that subfamily, so the IBA follows from descent. Two caveats are recorded. First, the experimentally characterized fly COMPASS subunit is Wdr82 (CG17293, FBgn0032030), which co-purifies with dSet1, dCXXC1, dDpy30, dRbbp5, Ash2 and Wds in S2 cells (PMID:21875999); CG3515 is not reported in those preparations. Second, CG3515 is highly diverged and testis-biased, so any COMPASS association is expected to be a testis-specific variant, which has not been tested. Absence from S2-cell purifications is not evidence of loss for a testis-biased protein, so the PAINT inference is retained.
MudPIT analysis of dWdr82-FLAG eluate showed the presence of all the homologous components of yeast COMPASS and human COMPASS, namely, dSet1, dCXXC1, dDpy30, dRbbp5, Ash2, and Wds
Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes.
file:DROME/CG3515/CG3515-uniprot.txt
DR PANTHER; PTHR19861:SF0; WD REPEAT-CONTAINING PROTEIN 82; 1.
Core Functions
Inferred non-catalytic WD40 subunit of a Set1/COMPASS-type H3K4 methyltransferase complex on nuclear chromatin, inherited from the Swd2/WDR82 subfamily. Not tested directly for this rapidly diverging, testis-biased paralog of fly Wdr82.
Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes.
file:DROME/CG3515/CG3515-uniprot.txt
DR PANTHER; PTHR19861:SF0; WD REPEAT-CONTAINING PROTEIN 82; 1.
Q: Does CG3515 assemble into a testis-specific Set1/COMPASS variant in place of, or alongside, Wdr82 in spermatocytes, or has it acquired a role outside COMPASS?
Q: At what point in insect evolution did the CG3515/Wdr82 duplication occur, and is the CG3515 lineage testis-biased across Drosophila species?
Suggested Experiments
Experiment: Affinity purification-mass spectrometry of tagged CG3515 from adult testes, compared with tagged Wdr82, to determine whether CG3515 co-purifies with dSet1, dCXXC1, Ash2, Rbbp5, Dpy30 and Wds.
Type: proteomics
Experiment: Germline-specific CG3515 knockdown or CRISPR null, assaying spermatocyte H3K4me3 levels and male fertility, with Wdr82 knockdown as comparator.
Type: genetic perturbation
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Nuclear localization is a reasonable conserved inference from the diagnostic Swd2/WDR82 family assignment and curated chromatin/COMPASS placement. Primary WDR82 experiments establish chromatin association and Set1-complex membership, providing the biological basis for that transfer. CG3515 is a separate fly paralog from Wdr82/CG17293, so these are not claimed as direct target experiments. The nucleus term is already present, making this supported prediction non-novel.
PMID:18838538: "We have shown that Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes."
PMID:21875999: "For either expression strategy, we isolated complexes by FLAG affinity purification from nuclear extracts from induced cells."