RNF14 (E3 ubiquitin-protein ligase RNF14; legacy name ARA54, androgen receptor-associated protein 54) is a cytosolic, ribosome-associated RING-in-between-RING (RBR)-type E3 ubiquitin ligase (EC 2.3.2.31). It contains an N-terminal RWD domain and a C-terminal TRIAD/RBR module (RING1, IBR, atypical RING2) and works with E2 enzymes of the UBE2D/UBE2E families. Its principal characterized function is in the RNF14-RNF25 translational quality-control pathway acting on stalled and collided ribosomes. Recruited to stalled ribosomes by the ribosome-collision sensor GCN1, RNF14 catalyzes atypical Lys-6 (K6)-linked ubiquitination of translation factors eEF1A (EEF1A1) and eRF1 (ETF1) and of ribosomal proteins, marking them for proteasomal degradation. It is specifically required to resolve reactive-aldehyde (e.g. formaldehyde)-induced RNA-protein crosslinks that stall ribosomes, by K6-ubiquitinating the crosslinked species for extraction by the VCP/p97 unfoldase and subsequent degradation. Independently of this co-translational surveillance role, RNF14 also acts in the nucleus as a transcriptional coregulator. It promotes Wnt/TCF-beta-catenin-mediated transcription via interaction with TCF7/TCF7L1/TCF7L2, and acts as a coactivator for androgen- (and to a lesser extent progesterone-) dependent transcription via interaction with the androgen receptor. It is widely expressed and undergoes RING-dependent autoubiquitination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0031624 ubiquitin conjugating enzyme binding | IBA GO_REF:0000033 | ACCEPT | Summary: As an RBR-type E3 ligase, RNF14 binds E2 ubiquitin-conjugating enzymes (UBE2E1/UBE2E2 experimentally; UBE2D family via interactome). E2 binding is mechanistically required for its ligase activity. Reason: Directly supported by documented interaction with the E2 enzymes UBE2E1/UBE2E2 and consistent with the RBR catalytic mechanism (E2 binds RING1, trans-thiolation to the RING2 active-site cysteine). This supports, but is subordinate to, the core ubiquitin ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Interacts with the ubiquitin-conjugating enzymes UBE2E1 and UBE2E2 |
| GO:0000151 ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Summary: RNF14 functions as the catalytic E3 within the RNF14-RNF25 ubiquitin ligase machinery that acts on stalled ribosomes, consistent with being part of a ubiquitin ligase complex. Reason: RNF14 is an E3 ligase that operates in concert with RNF25 and GCN1 on stalled ribosomes; the ubiquitin ligase complex localization is appropriate. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: General ubiquitin-protein transferase activity, the parent molecular function for RNF14's RBR E3 ligase catalysis. Reason: This generic transferase term is correct but less precise than the experimentally established ubiquitin protein ligase activity (GO:0061630). Generalize/replace with the specific ligase activity term that is supported by IDA evidence. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is documented and is associated with RNF14's transcriptional coregulator (Wnt/TCF and androgen-receptor) moonlighting roles. Reason: Nuclear localization is genuine but tied to the transcriptional/AR/Wnt moonlighting functions rather than the core cytosolic ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Nucleus {ECO:0000269|PubMed:9853615} |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is the compartment in which RNF14 acts on stalled ribosomes. Reason: Cytoplasmic localization is experimentally documented and is where the core RNF14-RNF25 ribosome-associated ligase function takes place. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: RNF14 coordinates multiple zinc ions through its RING1, IBR and atypical RING2 zinc fingers, which are structural for the RBR module. Reason: Zinc binding is a structural feature of the RBR zinc fingers; it is a true molecular property but is supportive/structural rather than the informative catalytic function. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt RING-type zinc finger-dependent and UBE2E2-dependent autoubiquitination |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Protein ubiquitination is the biological process carried out by RNF14's ligase activity. Reason: RNF14 mediates ubiquitination of translation factors and ribosomal proteins; the protein ubiquitination process term is correct, though the K6-linked subtype is more specific. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt PATHWAY: Protein modification; protein ubiquitination. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: RNF14 regulates Wnt/TCF-beta-catenin-mediated transcription through interaction with TCF transcription factors, a moonlighting role independent of its ribosome surveillance function. Reason: Supported by interaction with TCF7/TCF7L1/TCF7L2 and a documented role in colon cancer cell survival, but this is a secondary nuclear/transcriptional function distinct from the core ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ubiquitin protein ligase activity is the core molecular function of RNF14, independently established by multiple experimental studies. Reason: This is RNF14's defining molecular function (RBR-type E3 ligase, EC 2.3.2.31), corroborated by IDA evidence and active-site mutagenesis (Cys-220, Cys-417). Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0005515 protein binding | IPI PMID:19345326 Regulation of androgen receptor transcriptional activity and... | KEEP AS NON CORE | Summary: Interaction with the androgen receptor (AR, P10275) captured as bare protein binding. This underlies RNF14/ARA54's AR-coregulator role but the generic term is uninformative. Reason: The AR interaction is real and biologically meaningful for the AR-coactivator moonlighting role, but bare protein binding is uninformative; the AR-specific function is better captured by the dedicated nuclear androgen receptor binding annotation. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Interacts with AR/androgen receptor |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | KEEP AS NON CORE | Summary: High-throughput E2 interactome screen capturing interactions with the ubiquitin-conjugating enzymes UBE2D1 (P51668) and UBE2D4 (Q9Y2X8). Reason: The interaction partners are E2 enzymes, consistent with RNF14's RBR ligase mechanism, but bare protein binding is uninformative and the E2-binding function is already captured by ubiquitin conjugating enzyme binding. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:P51668 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale yeast two-hybrid interactome capturing RNF14 interactions (UBE2D1, DACH1, UBE2D4). Bare protein binding from a high-throughput screen. Reason: Records genuine interactions but bare protein binding is uninformative and does not define a specific function for this gene. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:Q9UI36-2 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Variant interactome screen capturing an RNF14-UBE2D4 (Q9Y2X8) interaction. Reason: An E2-enzyme interaction consistent with RNF14's ligase mechanism; bare protein binding is uninformative. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:Q9Y2X8 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI interactome screen capturing an RNF14-DACH1 (Q9UI36-2) interaction. Reason: Isolated high-throughput interaction; bare protein binding is uninformative and not part of the core function. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:Q9UI36-2 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Neurodegeneration interactome screen capturing interactions with PRKN/Parkin (O60260-5), GRN (P28799), TARDBP (Q13148) and RNF11 (Q9Y3C5). Reason: High-throughput interactions with disease-related proteins; bare protein binding is uninformative and these partners do not define RNF14's core function. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:O60260-5 |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Immunofluorescence (HPA) nucleoplasmic localization, consistent with RNF14's nuclear transcriptional moonlighting role. Reason: Genuine localization tied to the nuclear transcriptional/AR/Wnt functions rather than the core cytosolic ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt GO:0005654; C:nucleoplasm |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (HPA) cytosolic localization, the compartment where RNF14 acts on stalled ribosomes. Reason: Cytosolic localization corresponds to the core ribosome-associated ligase function and is supported by direct evidence. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt GO:0005829; C:cytosol |
| GO:0022626 cytosolic ribosome | IDA PMID:36638793 An E3 ligase network engages GCN1 to promote the degradation... | ACCEPT | Summary: RNF14 is active at the cytosolic ribosome, where it ubiquitinates translation factors and ribosomal proteins on stalled ribosomes. Reason: Directly supported by the GCN1-dependent recruitment of RNF14 to stalled ribosomes and ubiquitination of ribosomal proteins; this is the core site of action. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Recruited to stalled ribosomes by the ribosome collision sensor GCN1 |
| GO:0160127 protein-RNA covalent cross-linking repair | IDA PMID:37951215 K6-linked ubiquitylation marks formaldehyde-induced RNA-prot... | ACCEPT | Summary: RNF14 K6-ubiquitinates reactive-aldehyde-induced RNA-protein crosslinks that stall ribosomes, marking them for VCP-dependent extraction and resolution. Reason: Directly demonstrated; RNF14 is specifically required to resolve formaldehyde-induced RNA-protein crosslinks. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Specifically required to resolve RNA-protein cross-links caused by reactive aldehydes |
| GO:0160127 protein-RNA covalent cross-linking repair | IDA PMID:37951216 RNF14-dependent atypical ubiquitylation promotes translation... | ACCEPT | Summary: Independent study showing RNF14-dependent atypical ubiquitylation promotes translation-coupled resolution of RNA-protein crosslinks. Reason: Corroborated by a second independent study demonstrating RNF14's role in resolving RNA-protein crosslinks. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Specifically required to resolve RNA-protein cross-links caused by reactive aldehydes |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:37651229 Drug-induced eRF1 degradation promotes readthrough and revea... | ACCEPT | Summary: Direct demonstration of RNF14 E3 ligase catalytic activity, with Cys-220 active-site mutagenesis, in the eRF1-degradation branch of ribosome quality control. Reason: Core molecular function established by IDA with catalytic-cysteine mutagenesis. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:37951215 K6-linked ubiquitylation marks formaldehyde-induced RNA-prot... | ACCEPT | Summary: Direct demonstration that RNF14 (RBR E3 ligase) catalyzes atypical K6-linked ubiquitylation of formaldehyde-induced crosslinks. Reason: Core molecular function established by direct biochemical evidence. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:37951216 RNF14-dependent atypical ubiquitylation promotes translation... | ACCEPT | Summary: Independent direct demonstration of RNF14-dependent atypical ubiquitylation activity in RNA-protein crosslink resolution. Reason: Core molecular function corroborated by a second independent study. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:37651229 Drug-induced eRF1 degradation promotes readthrough and revea... | ACCEPT | Summary: RNF14 participates in resolving stalled ribosomes by ubiquitinating and degrading translation factors (eRF1/eEF1A) on them. Reason: Core biological-process role; RNF14 is required for the translational stress response to stalled ribosomes. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt promotes ubiquitination and degradation of translation factors on stalled ribosomes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:37951215 K6-linked ubiquitylation marks formaldehyde-induced RNA-prot... | ACCEPT | Summary: RNF14 resolves stalled ribosomes caused by RNA-protein crosslinks via K6 ubiquitination and VCP extraction. Reason: Core biological-process role supported by direct evidence in the crosslink-resolution context. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt which trigger translation stress by stalling ribosomes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:37951216 RNF14-dependent atypical ubiquitylation promotes translation... | ACCEPT | Summary: Independent demonstration of RNF14's role in translation-coupled resolution of stalled ribosomes. Reason: Core biological-process role corroborated by a second independent study. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt which trigger translation stress by stalling ribosomes |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:37951215 K6-linked ubiquitylation marks formaldehyde-induced RNA-prot... | ACCEPT | Summary: RNF14 catalyzes atypical Lys-6 (K6)-linked ubiquitination, the signature ubiquitin-chain type it produces on stalled-ribosome substrates and crosslinks. Reason: Core, mechanistically distinctive activity directly demonstrated; K6-linked ubiquitylation marks formaldehyde-induced crosslinks for resolution. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt mediates 'Lys-6'-linked ubiquitination of target proteins |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:37951216 RNF14-dependent atypical ubiquitylation promotes translation... | ACCEPT | Summary: Independent demonstration of RNF14-mediated K6-linked ubiquitination. Reason: Core distinctive activity corroborated by a second independent study. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt mediates 'Lys-6'-linked ubiquitination of target proteins |
| GO:0060828 regulation of canonical Wnt signaling pathway | IDA PMID:23449499 Ring Finger Protein 14 is a new regulator of TCF/beta-cateni... | KEEP AS NON CORE | Summary: RNF14 regulates TCF/beta-catenin-mediated (canonical Wnt) transcription and colon cancer cell survival via interaction with TCF transcription factors. Reason: A genuine, experimentally supported nuclear transcriptional role, but a moonlighting function distinct from the core cytosolic ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: RNF14-mediated ubiquitination targets substrates (stalled-ribosome translation factors and crosslinks) for proteasomal degradation. Reason: The ubiquitin-dependent catabolic outcome of RNF14's ligase activity is directly supported; substrates are degraded by the proteasome. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt leading to their degradation |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:36638793 An E3 ligase network engages GCN1 to promote the degradation... | ACCEPT | Summary: RNF14 promotes degradation of translation factors on stalled ribosomes, a ubiquitin-dependent catabolic process. Reason: Directly supported; the GCN1-RNF14 pathway promotes degradation of eEF1A/eRF1 and ribosomal proteins. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt promotes ubiquitination and degradation of translation factors on stalled ribosomes |
| GO:0022626 cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: RNF14 is active at the cytosolic ribosome. Reason: Consistent with the GCN1-dependent recruitment to stalled ribosomes; core site of action. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Recruited to stalled ribosomes by the ribosome collision sensor GCN1 |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: Direct demonstration of RNF14 ubiquitin protein ligase activity. Reason: Core molecular function established by direct evidence. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:36638793 An E3 ligase network engages GCN1 to promote the degradation... | ACCEPT | Summary: Direct demonstration of RNF14 catalytic ligase activity with Cys-417 active-site mutagenesis in the GCN1-engaged stalled-ribosome pathway. Reason: Core molecular function established by IDA with catalytic-cysteine mutagenesis. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt E3 ubiquitin-protein ligase that plays a key role in the |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: RNF14 participates in the response to stalled ribosomes. Reason: Core biological-process role supported by direct evidence. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt promotes ubiquitination and degradation of translation factors on stalled ribosomes |
| GO:0072344 rescue of stalled cytosolic ribosome | IDA PMID:36638793 An E3 ligase network engages GCN1 to promote the degradation... | ACCEPT | Summary: RNF14, engaged by GCN1, acts to resolve stalled ribosomes by degrading translation factors. Reason: Core biological-process role; foundational study defining the GCN1-RNF14-RNF25 pathway. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Recruited to stalled ribosomes by the ribosome collision sensor GCN1 |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:27863242 Decoding Mammalian Ribosome-mRNA States by Translational GTP... | ACCEPT | Summary: RNF14 catalyzes K6-linked ubiquitination. Reason: Core distinctive activity supported by direct evidence. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt mediates 'Lys-6'-linked ubiquitination of target proteins |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:19345326 Regulation of androgen receptor transcriptional activity and... | KEEP AS NON CORE | Summary: RNF14/ARA54 functions as a transcriptional coregulator of androgen-receptor-dependent transcription. Reason: A genuine but moonlighting transcriptional role tied to AR/Wnt coregulation, distinct from the core cytosolic ligase function. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt May also play a role as a coactivator for androgen- |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:19345326 Regulation of androgen receptor transcriptional activity and... | KEEP AS NON CORE | Summary: RNF14/ARA54 acts as a coactivator, positively regulating androgen-receptor-dependent transcription. Reason: A coactivator (positive-regulation) role consistent with the AR moonlighting function; non-core relative to the ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt May also play a role as a coactivator for androgen- |
| GO:0050681 nuclear androgen receptor binding | IPI PMID:19345326 Regulation of androgen receptor transcriptional activity and... | KEEP AS NON CORE | Summary: RNF14/ARA54 binds the androgen receptor, the molecular basis for its AR-coactivator role; the C-terminal region (residues 361-474) mediates this interaction. Reason: A genuine, specific interaction underpinning the AR-coregulator moonlighting function; informative but non-core relative to the ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Interacts with AR/androgen receptor |
| GO:0060765 regulation of androgen receptor signaling pathway | IDA PMID:19345326 Regulation of androgen receptor transcriptional activity and... | KEEP AS NON CORE | Summary: RNF14/ARA54 modulates androgen-receptor signaling/transcriptional output. Reason: Part of the AR-coregulator moonlighting role; genuine but non-core. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt coactivator for androgen- |
| GO:0016567 protein ubiquitination | IEP PMID:11322894 N-terminally extended human ubiquitin-conjugating enzymes (E... | ACCEPT | Summary: Early characterization of ARA54/RNF14 as a RING-finger protein undergoing E2-dependent (auto)ubiquitination. Reason: Protein ubiquitination is consistent with RNF14's ligase function (including RING-dependent, UBE2E2-dependent autoubiquitination). Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt RING-type zinc finger-dependent and UBE2E2-dependent autoubiquitination |
| GO:0005515 protein binding | IPI PMID:10085091 Cloning and characterization of human prostate coactivator A... | KEEP AS NON CORE | Summary: Original ARA54 study; interaction captured here is with O14933 (UBE2L6), a ubiquitin-conjugating enzyme. Bare protein binding term. Reason: An E2-related interaction consistent with the ligase mechanism, but bare protein binding is uninformative. Supporting Evidence: file:human/RNF14/RNF14-goa.tsv UniProtKB:O14933 |
| GO:0030521 androgen receptor signaling pathway | NAS PMID:11322894 N-terminally extended human ubiquitin-conjugating enzymes (E... | KEEP AS NON CORE | Summary: Non-traceable-author statement placing ARA54/RNF14 in the androgen-receptor signaling pathway. Reason: Consistent with the AR-coregulator moonlighting role; retained as non-core. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Interacts with AR/androgen receptor |
| GO:0003713 transcription coactivator activity | TAS PMID:10085091 Cloning and characterization of human prostate coactivator A... | KEEP AS NON CORE | Summary: RNF14/ARA54 was originally described as a transcriptional coactivator for the androgen receptor. Reason: A genuine moonlighting molecular function (coactivator) tied to AR-dependent transcription; non-core relative to the ribosome-associated ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt coactivator for androgen- |
| GO:0005634 nucleus | IDA PMID:11322894 N-terminally extended human ubiquitin-conjugating enzymes (E... | KEEP AS NON CORE | Summary: Direct evidence of nuclear localization, consistent with the transcriptional moonlighting role. Reason: Genuine localization associated with the nuclear/transcriptional functions rather than the core cytosolic ligase activity. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Nucleus {ECO:0000269|PubMed:9853615} |
| GO:0005737 cytoplasm | IDA PMID:11322894 N-terminally extended human ubiquitin-conjugating enzymes (E... | ACCEPT | Summary: Direct evidence of cytoplasmic localization, the compartment of the core ribosome-associated ligase function. Reason: Cytoplasmic localization supported by direct evidence and corresponds to RNF14's core site of action. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0006357 regulation of transcription by RNA polymerase II | TAS PMID:10085091 Cloning and characterization of human prostate coactivator A... | KEEP AS NON CORE | Summary: RNF14/ARA54 as a coregulator of RNA polymerase II-dependent (androgen-receptor) transcription. Reason: Consistent with the transcriptional coregulator moonlighting role; non-core. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt coactivator for androgen- |
| GO:0007165 signal transduction | TAS PMID:10085091 Cloning and characterization of human prostate coactivator A... | MARK AS OVER ANNOTATED | Summary: Very generic signal transduction term from the original ARA54 study, reflecting its role in hormone-receptor signaling. Reason: Signal transduction is too generic to be informative for this gene; the more specific androgen-receptor signaling annotations already capture the relevant role. Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt Interacts with AR/androgen receptor |
| GO:0019787 ubiquitin-like protein transferase activity | IDA PMID:11322894 N-terminally extended human ubiquitin-conjugating enzymes (E... | MODIFY | Summary: Early characterization of ARA54/RNF14 E2-dependent ubiquitin transfer activity, annotated with the broader ubiquitin-like transferase term. Reason: RNF14 transfers ubiquitin (not other UBLs); the broader ubiquitin-like protein transferase term should be replaced by the specific ubiquitin protein ligase activity established by later experimental work. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: file:human/RNF14/RNF14-uniprot.txt RING-type zinc finger-dependent and UBE2E2-dependent autoubiquitination |
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Download this section (compressed HTML)Q: What determines RNF14 substrate selection (eEF1A vs eRF1 vs ribosomal proteins vs RNA-protein crosslinks) on stalled ribosomes, and how is this coordinated with RNF25?
Q: Is the nuclear transcriptional coregulator role (AR/Wnt) mechanistically dependent on RNF14 ligase activity, or is it a ligase-independent scaffolding function?
Q: How is the choice of K6-linked chain topology achieved by the atypical RBR module that lacks the canonical RING2 histidine?
Experiment: Ribosome profiling and quantitative ubiquitin-site proteomics in RNF14 and RNF14/RNF25 double knockouts after formaldehyde or stalling stress to map the full K6-ubiquitinated substrate set.
Experiment: Structure-function analysis (cryo-EM of RNF14-GCN1-stalled ribosome complexes) to define how GCN1 recruits and positions RNF14 on collided ribosomes.
Experiment: Separation-of-function mutants (catalytic-dead Cys-417/Cys-220 vs AR/TCF-binding-deficient C-terminal mutants) to test whether the transcriptional moonlighting roles require ligase activity.
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