Elongin C (EloC) is a small Skp1-like protein that, together with the ubiquitin-like Elongin B, forms the EloB/C heterodimer. EloB/C serves two roles: as the adaptor of cullin-RING ligases, EloC binds the BC-box of substrate receptors such as Vhl, SOCS-box proteins (Socs36E) and the ZSWIM8 ortholog Dora, and links them to Cul2 (or Cul5) and the RING protein Roc1a, forming ligases such as the VCB-Cul2 complex that ubiquitinates HIF-alpha/Sima, the Cul5-Socs36E ligase that dampens JAK/STAT signaling, and a Dora ligase required for target-directed miRNA degradation; and, with Elongin A, as part of the Elongin transcription elongation complex that increases RNA polymerase II elongation. EloC was isolated as a two-hybrid partner of the chromatin factor Corto and co-immunoprecipitates with it. In the wing, EloC and Corto both occupy the rhomboid locus, and EloC acts with EloA/B in vein versus intervein specification, antagonizing corto genetically. EloC is found in the nucleus and cytoplasm.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003682 chromatin binding | IDA PMID:24204884 The elongin complex antagonizes the chromatin factor Corto f... | KEEP AS NON CORE | Summary: Chromatin binding (ChIP at rhomboid). Reason: ChIP shows EloC at the vein-promoting gene rhomboid in wing discs, consistent with the Elongin transcription elongation complex; accurate but peripheral to the ligase adaptor role. Supporting Evidence: PMID:24204884 Chromatin immunoprecipitation experiments indicate that Elongin C and Corto bind the vein-promoting gene rhomboid in wing imaginal discs. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus. Reason: Consistent with Elongin complex function at chromatin and nuclear CRL substrates. The UniProt location line is an ARBA prediction and is not cited; direct support is that Myc-tagged fly EloC binds polytene chromosomes (nuclear chromatin) and tagged Elongin proteins were mainly detected in S2-cell nuclear extracts. Supporting Evidence: PMID:24204884 We show that EloC, like EloA, binds polytene chromosomes PMID:24204884 These were mainly detected in nuclear extracts of S2 cells |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoplasm (ARBA). Reason: Consistent with cytoplasmic CRL2/CRL5 substrates such as Sima and the Dome receptor. |
| GO:0006368 transcription elongation by RNA polymerase II | IC PMID:24204884 The elongin complex antagonizes the chromatin factor Corto f... | ACCEPT | Summary: Transcription elongation by RNA polymerase II (IC from elongin complex). Reason: Inferred from Elongin complex membership; EloB/C stimulate Pol II elongation with EloA in mammals. In flies the evidence is genetic and ChIP-based; accepted as the second, transcriptional role of EloB/C. Supporting Evidence: PMID:24204884 This complex, that consists of three subunits (Elongin A, B, C), increases RNA polymerase II elongation rate in vitro by suppressing transient pausing. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Ubiquitin-dependent protein catabolic process (InterPro SKP1-like). Reason: Correct but less specific than the evidence supports: EloC-containing Cul2 ligases target substrates such as HIF-alpha for proteasomal degradation. MODIFY to GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process. Proposed replacements: proteasome-mediated ubiquitin-dependent protein catabolic process |
| GO:0007474 imaginal disc-derived wing vein specification | IGI PMID:24204884 The elongin complex antagonizes the chromatin factor Corto f... | KEEP AS NON CORE | Summary: Wing vein specification. Reason: EloB and EloC heterozygotes truncate L5 and interact genetically with corto; developmental output, non-core. Supporting Evidence: PMID:24204884 EloC heterozygous females presented the same phenotype, although less penetrant |
| GO:0016032 viral process | IGI PMID:30308158 A Viral Protein Restricts Drosophila RNAi Immunity by Regula... | KEEP AS NON CORE | Summary: Viral process (CrPV-1A co-opting the host Cul2-EloBC ligase). Reason: GO:0016032 is the term for host gene products that take part in a viral life cycle. Cricket paralysis virus 1A uses a BC-box to recruit the host Cul2-Rbx1-EloBC ligase (including EloC) to degrade Ago-2 and promote viral replication, so EloC genuinely participates in the viral process (virus co-opting host ligase function). Correct but not a core function of EloC. Supporting Evidence: PMID:30308158 CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. |
| GO:0031462 Cul2-RING ubiquitin ligase complex | IDA PMID:23102700 The Kelch repeat protein KLHDC10 regulates oxidative stress-... | ACCEPT | Summary: Cul2-RING complex (KLHDC10/Slim paper). Reason: Abstract-only cache does not mention EloC; it describes a fly misexpression screen that identified Slim and a proteomics screen with its mammalian ortholog KLHDC10. KLHDC10 is a Cul2-EloB/C substrate receptor, and Cul2-RING membership of EloC is independently supported by PMID:30308158. Accepted deferring to the curator; the evidence code is queried below. Supporting Evidence: PMID:30308158 CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. |
| GO:0031462 Cul2-RING ubiquitin ligase complex | IPI PMID:30308158 A Viral Protein Restricts Drosophila RNAi Immunity by Regula... | ACCEPT | Summary: Cul2-RING ubiquitin ligase complex. Reason: EloC is the BC-box adaptor of Cul2-RING ligases (VCB-Cul2). Supporting Evidence: PMID:30308158 E3 ubiquitin ligase complexes containing Cul2, EloB+EloC (herein EloBC), and Rbx1, recruit their substrates through exchangeable substrate receptors. |
| GO:0031463 Cul3-RING ubiquitin ligase complex | IDA PMID:40328417 Insights into the target-directed miRNA degradation mechanis... | ACCEPT | Summary: Cul3-RING ubiquitin ligase complex (Dora/ZSWIM8 ligase). Reason: The Dora-containing TDMD ligase was described as a CRL3 containing Cul3, EloB and EloC; accepted as reported (in humans the ZSWIM8 ligase is Cul3-EloB/C based). Supporting Evidence: PMID:40328417 We also showed that Dora associates with proteins of the CRL3 complex, and the depletion of CRL3 components or inhibition of Cul3 neddylation upregulates miR-7-5p. |
| GO:0046426 negative regulation of receptor signaling pathway via JAK-STAT | IMP PMID:23885117 Drosophila SOCS36E negatively regulates JAK/STAT pathway sig... | KEEP AS NON CORE | Summary: Negative regulation of JAK-STAT signaling. Reason: EloB/C with Cul5 act via the Socs36E SOCS-box to reduce ligand-stimulated JAK/STAT activity; pathway output, non-core. Supporting Evidence: PMID:23885117 Drosophila Elongin B/C and Cullin-5 act via the SOCS-box of SOCS36E to reduce pathway activity specifically in response to ligand stimulation |
| GO:0070449 elongin complex | IDA PMID:24204884 The elongin complex antagonizes the chromatin factor Corto f... | ACCEPT | Summary: Elongin complex. Reason: EloC is a subunit of the Elongin (EloA/B/C) transcription elongation complex. Supporting Evidence: PMID:24204884 We show here that Corto interacts with the Elongin transcription elongation complex. This complex, that consists of three subunits (Elongin A, B, C) |
| GO:0140535 intracellular protein-containing complex | IEA GO_REF:0000117 | MODIFY | Summary: Intracellular protein-containing complex (ARBA). Reason: Correct but uninformative; the evidence supports the specific complexes this protein belongs to: VCB (GO:0030891), Elongin (GO:0070449), Cul2-RING (GO:0031462) and the Dora Cul3-RING ligase (GO:0031463). The last three are already annotated to this gene; VCB is a proposed addition, as EloC is a constitutive VCB subunit. MODIFY to these. Proposed replacements: VCB complex elongin complex Cul2-RING ubiquitin ligase complex Cul3-RING ubiquitin ligase complex |
| GO:0140958 target-directed miRNA degradation | IMP PMID:40328417 Insights into the target-directed miRNA degradation mechanis... | KEEP AS NON CORE | Summary: Target-directed miRNA degradation. Reason: Depleting CRL3 components including EloC upregulates miR-7-5p in OSCs; a specific output of the Dora ligase, non-core. Supporting Evidence: PMID:40328417 We also showed that Dora associates with proteins of the CRL3 complex, and the depletion of CRL3 components or inhibition of Cul3 neddylation upregulates miR-7-5p. |
| GO:1990234 transferase complex | IEA GO_REF:0000117 | MODIFY | Summary: Transferase complex (ARBA). Reason: Correct but less specific than the evidence supports; MODIFY to GO:0031462 Cul2-RING ubiquitin ligase complex, which EloC already carries. Proposed replacements: Cul2-RING ubiquitin ligase complex |
Loading supporting content…
Download this section (compressed HTML)Q: Is the fly Dora/ZSWIM8 TDMD ligase built on Cul3 (as reported) or on Cul2/Cul5, given that EloB/C usually partner with Cul2/Cul5?
Q: Does fly EloC contribute to Pol II elongation in vivo independently of its CRL adaptor role, for example at rhomboid?
Experiment: Compare wing-vein phenotypes and rhomboid Pol II elongation (PRO-seq/ChIP) in EloA, Vhl, Cul2 and Cul5 knockdowns versus EloC knockdown.
Hypothesis: EloC acts at rhomboid as part of the Elongin elongation complex rather than as a CRL adaptor.
Loading supporting content…
Download this section (compressed HTML)Elongin C (EloC) encodes an essential protein for development that participates in the control of wing cell identity. EloB, EloC and EloA encode for subunits of the Elongin complex, which interacts in vivo with the chromatin factor encoded by corto.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)