ARMC5

Summary: Chromatin (IDA). ARMC5 acts on chromatin-bound, promoter-proximal Pol II. GFP ChIP-seq shows ARMC5 occupancy at promoter-proximal regions when SPT5 is depleted, which CDK9 inhibition reduces. Crosslinking also recovers ARMC5 in the chromatin fraction with RPB1, although most ARMC5 is soluble at steady state. Accepted as a site of its activity.

Reason: [PMID:39854452 "Using an unbiased proteomic screening approach, we identify armadillo repeat-containing 5 (ARMC5) as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, chromatin-bound Pol II."] [PMID:39854452 "Compared to the high levels of signal observed upon single auxin treatment, ARMC5 ChIP-seq signal was largely decreased by double treatment with NVP-2 and auxin (Fig."] [PMID:39854452 "Thus, CDK9 kinase activity appears to regulate ARMC5 recruitment to promoter-proximal Pol II, in good agreement with our initial MS results (Fig. 1D)."] [PMID:39667934 "However, when crosslinker dithiobis (succinimidyl propionate) (DSP) was used,68 ARMC5 could also be detected in the chromatin fraction, along with the interaction between ARMC5 and RPB1 (Figure 5D)."] [PMID:39667934 "This indicates that ARMC5 is found predominantly in the soluble fraction, where it interacts with RNA Pol II, but it may also transiently interact with RNA Pol II on chromatin."]

Summary: Protein binding (IPI) with RPN2, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with POLR2A (RPB1), from the yeast two-hybrid screen in the Armc5 knockout study. RPB1 is the principal substrate of CRL3-ARMC5, and that recognition is captured by the ubiquitin-like ligase-substrate adaptor activity rows. The generic row is removed under the policy; removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy. The substrate relationship is captured elsewhere: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Protein binding (IPI) with KIF11, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with DAPK1, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with CUL3, from the yeast two-hybrid screen in the Armc5 knockout study. ARMC5 binds CUL3 through its BTB domain to form the CRL3-ARMC5 ubiquitin ligase. Modified to cullin family protein binding.

Reason: [PMID:32023208 "In this study, we showed that ARMC5 interacts with CUL3 requiring its BTB domain."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Proposed replacements: cullin family protein binding

Summary: Protein binding (IPI) with E2F2, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with TTF1, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with PCBP1, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with ERCC6L, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with HUWE1, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with CACUL1, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with ARMC5 (self), from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with CDCA7L, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with TCF12, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with ZBTB40, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with RIPOR2, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with STK24, from the yeast two-hybrid screen in the Armc5 knockout study. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with TLX3, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with PRR35, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with COL8A1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with MKRN3, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with GLYCTK, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with USHBP1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with SPAG8, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with ENKD1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Protein binding (IPI) with CNOT2, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.

Summary: Nucleus (EXP). ARMC5 shuttles between cytosol and nucleus. It is seen in nuclei by immunofluorescence, and becomes prominent there when nuclear export is blocked, consistent with its targeting of Pol II. Core location.

Reason: [PMID:35687106 "This suggested that ARMC5 did enter the nuclei, but that there was also active shuttling of ARMC5 between the cytosol and nuclei."] [PMID:38225631 "C ARMC5 was detected in both cytosol and nuclei."]

Summary: Nucleus (IDA). ARMC5 shuttles between cytosol and nucleus. It is seen in nuclei by immunofluorescence, and becomes prominent there when nuclear export is blocked, consistent with its targeting of Pol II. Core location.

Reason: [PMID:35687106 "This suggested that ARMC5 did enter the nuclei, but that there was also active shuttling of ARMC5 between the cytosol and nuclei."] [PMID:38225631 "C ARMC5 was detected in both cytosol and nuclei."]

Summary: Nucleus (IDA). ARMC5 shuttles between cytosol and nucleus. It is seen in nuclei by immunofluorescence, and becomes prominent there when nuclear export is blocked, consistent with its targeting of Pol II. Core location.

Reason: [PMID:35687106 "This suggested that ARMC5 did enter the nuclei, but that there was also active shuttling of ARMC5 between the cytosol and nuclei."] [PMID:38225631 "C ARMC5 was detected in both cytosol and nuclei."]

Summary: Nucleus (IEA). ARMC5 shuttles between cytosol and nucleus. It is seen in nuclei by immunofluorescence, and becomes prominent there when nuclear export is blocked, consistent with its targeting of Pol II. Core location.

Reason: [PMID:35687106 "This suggested that ARMC5 did enter the nuclei, but that there was also active shuttling of ARMC5 between the cytosol and nuclei."] [PMID:38225631 "C ARMC5 was detected in both cytosol and nuclei."]

Summary: Chromosome (EXP). ARMC5 acts on chromatin-bound, promoter-proximal Pol II. GFP ChIP-seq shows ARMC5 occupancy at promoter-proximal regions when SPT5 is depleted, which CDK9 inhibition reduces. Crosslinking also recovers ARMC5 in the chromatin fraction with RPB1, although most ARMC5 is soluble at steady state. Accepted as a site of its activity.

Reason: [PMID:39854452 "Using an unbiased proteomic screening approach, we identify armadillo repeat-containing 5 (ARMC5) as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, chromatin-bound Pol II."] [PMID:39854452 "Compared to the high levels of signal observed upon single auxin treatment, ARMC5 ChIP-seq signal was largely decreased by double treatment with NVP-2 and auxin (Fig."] [PMID:39854452 "Thus, CDK9 kinase activity appears to regulate ARMC5 recruitment to promoter-proximal Pol II, in good agreement with our initial MS results (Fig. 1D)."] [PMID:39667934 "However, when crosslinker dithiobis (succinimidyl propionate) (DSP) was used,68 ARMC5 could also be detected in the chromatin fraction, along with the interaction between ARMC5 and RPB1 (Figure 5D)."] [PMID:39667934 "This indicates that ARMC5 is found predominantly in the soluble fraction, where it interacts with RNA Pol II, but it may also transiently interact with RNA Pol II on chromatin."]

Summary: Chromosome (IEA). ARMC5 acts on chromatin-bound, promoter-proximal Pol II. GFP ChIP-seq shows ARMC5 occupancy at promoter-proximal regions when SPT5 is depleted, which CDK9 inhibition reduces. Crosslinking also recovers ARMC5 in the chromatin fraction with RPB1, although most ARMC5 is soluble at steady state. Accepted as a site of its activity.

Reason: [PMID:39854452 "Using an unbiased proteomic screening approach, we identify armadillo repeat-containing 5 (ARMC5) as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, chromatin-bound Pol II."] [PMID:39854452 "Compared to the high levels of signal observed upon single auxin treatment, ARMC5 ChIP-seq signal was largely decreased by double treatment with NVP-2 and auxin (Fig."] [PMID:39854452 "Thus, CDK9 kinase activity appears to regulate ARMC5 recruitment to promoter-proximal Pol II, in good agreement with our initial MS results (Fig. 1D)."] [PMID:39667934 "However, when crosslinker dithiobis (succinimidyl propionate) (DSP) was used,68 ARMC5 could also be detected in the chromatin fraction, along with the interaction between ARMC5 and RPB1 (Figure 5D)."] [PMID:39667934 "This indicates that ARMC5 is found predominantly in the soluble fraction, where it interacts with RNA Pol II, but it may also transiently interact with RNA Pol II on chromatin."]

Summary: Cytoplasm (IDA). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:24283224 "Immunohistochemical analysis of adrenal samples and two cell lines (H295R and HeLa) showed that ARMC5 is mostly located in the cytoplasm (Fig."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Cytoplasm (IDA). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:35687106 "This suggested that ARMC5 did enter the nuclei, but that there was also active shuttling of ARMC5 between the cytosol and nuclei."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Cytoplasm (IDA). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Cytoplasm (IDA). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:38225631 "C ARMC5 was detected in both cytosol and nuclei."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Cytoplasm (IEA). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:24283224 "Immunohistochemical analysis of adrenal samples and two cell lines (H295R and HeLa) showed that ARMC5 is mostly located in the cytoplasm (Fig."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Cytoplasm (IMP). ARMC5 is mostly cytoplasmic in adrenal tissue and cell lines, co-localizes with SREBF1 in the cytosol, and shuttles to the nucleus. Core location.

Reason: [PMID:24283224 "Immunohistochemical analysis of adrenal samples and two cell lines (H295R and HeLa) showed that ARMC5 is mostly located in the cytoplasm (Fig."] [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."]

Summary: Anatomical structure morphogenesis (IBA). Armc5 knockout causes embryonic lethality and developmental defects in mice, and ARMC5 mutations raise neural tube defect risk in mice and humans. The term is broad, but ARMC5 is genuinely required for normal development, likely through Pol II dosage control. Kept as a non-core developmental role.

Reason: [PMID:28169274 "This suggested that Armc5 deletion caused embryonic lethality, with its severity depending on genetic background of the mice: embryonic lethality became more severe with higher degrees of genetic background purity."] [PMID:38225631 "CONCLUSIONS: Mutations in ARMC5 increase the risk of NTDs in mice and humans."]

Summary: Membrane (IEA, from mouse Armc5). The donor IDA cites an Armc5 haploinsufficiency study whose cached abstract reports no membrane localization; the full text was not available to check. UniProt's curated human locations are nucleus, chromosome and cytoplasm, with no transmembrane segment annotated. Left undecided.

Reason: [PMID:28911199 "We generated and characterized a new mouse model of Armc5 deficiency."] [PMID:24283224 "Immunohistochemical analysis of adrenal samples and two cell lines (H295R and HeLa) showed that ARMC5 is mostly located in the cytoplasm (Fig."]

Summary: Protein ubiquitination (IEA, UniPathway). Correct but broad: ARMC5 is the substrate receptor of a CRL3 ligase, and the specific roles are captured by the adaptor and proteasomal-degradation rows. Kept as non-core.

Reason: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Cul3-RING ubiquitin ligase complex (IDA). ARMC5 forms an active E3 with CUL3 and RBX1 (CRL3-ARMC5); core location.

Reason: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Cul3-RING ubiquitin ligase complex (IDA). ARMC5 forms an active E3 with CUL3 and RBX1 (CRL3-ARMC5); core location.

Reason: [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Cul3-RING ubiquitin ligase complex (IDA). ARMC5 forms an active E3 with CUL3 and RBX1 (CRL3-ARMC5); core location.

Reason: [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Cul3-RING ubiquitin ligase complex (IDA). ARMC5 forms an active E3 with CUL3 and RBX1 (CRL3-ARMC5); core location.

Reason: [PMID:39504960 "Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3ARMC5 E3 ligase, which ubiquitylates CTD serine5-phosphorylated RPB1 for degradation."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Cul3-RING ubiquitin ligase complex (IDA). ARMC5 forms an active E3 with CUL3 and RBX1 (CRL3-ARMC5); core location.

Reason: [PMID:39667934 "Here, we reveal a distinct ubiquitylation pathway in human cells, mediated by CRL3ARMC5, that targets excessive and defective RNA Pol II molecules at the initial stages of the transcription cycle."] [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IDA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:35687106 "Armc5 deletion caused a significant reduction in RPB1 ubiquitination and an increase in an accumulation of RPB1, and hence an enlarged Pol II pool in normal tissues and organs."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IDA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:35862218 "ARMC5 colocalized with SREBF1 in the cytosol and induced proteasome-dependent degradation of full-length SREBF through ubiquitination."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IDA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IDA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:39504960 "Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3ARMC5 E3 ligase, which ubiquitylates CTD serine5-phosphorylated RPB1 for degradation."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IDA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:39667934 "Here, we reveal a distinct ubiquitylation pathway in human cells, mediated by CRL3ARMC5, that targets excessive and defective RNA Pol II molecules at the initial stages of the transcription cycle."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IEA). As the substrate receptor, CRL3-ARMC5 ubiquitinates Pol II subunits and full-length SREBF for proteasomal degradation, and its loss stabilizes them. Core process.

Reason: [PMID:35687106 "Armc5 deletion caused a significant reduction in RPB1 ubiquitination and an increase in an accumulation of RPB1, and hence an enlarged Pol II pool in normal tissues and organs."] [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."]

Summary: Ubiquitin protein ligase activity (IEA, from mouse Armc5). The CRL3-ARMC5 complex has ligase activity, but ARMC5 is its BTB substrate receptor, not the RING subunit. Its own activity is ubiquitin-like ligase-substrate adaptor activity; modified to that term, which merges this row with the GO:1990756 IEA row from the same mouse donor.

Reason: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."] [PMID:39491648 "ARMC5-CUL3 complex was recently identified as E3 ubiquitin ligase of full-length SREBF."]

Proposed replacements: ubiquitin-like ligase-substrate adaptor activity

Summary: RNA polymerase II transcription initiation surveillance (IDA). CRL3-ARMC5 removes excess and defective Pol II at the promoter-proximal stage, in parallel with Integrator, and is activated by defects in pause-associated factors. Core process.

Reason: [PMID:39504960 "ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme."] [PMID:39667934 "These findings uncover CRL3ARMC5 and Integrator as two distinct pathways acting in parallel to monitor the quantity and quality of transcription complexes before they are licensed into elongation."]

Summary: RNA polymerase II transcription initiation surveillance (IDA). CRL3-ARMC5 removes excess and defective Pol II at the promoter-proximal stage, in parallel with Integrator, and is activated by defects in pause-associated factors. Core process.

Reason: [PMID:39667934 "Here, we reveal a distinct ubiquitylation pathway in human cells, mediated by CRL3ARMC5, that targets excessive and defective RNA Pol II molecules at the initial stages of the transcription cycle."] [PMID:39667934 "These findings uncover CRL3ARMC5 and Integrator as two distinct pathways acting in parallel to monitor the quantity and quality of transcription complexes before they are licensed into elongation."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IDA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IDA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:35862218 "In this study, through biochemical purification using SREBF (SREBP) as bait, we identified the interaction between SREBF and ARMC5 through its Armadillo repeat."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IDA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:38225631 "Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IDA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:39504960 "Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3ARMC5 E3 ligase, which ubiquitylates CTD serine5-phosphorylated RPB1 for degradation."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IDA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:39667934 "Here, we reveal a distinct ubiquitylation pathway in human cells, mediated by CRL3ARMC5, that targets excessive and defective RNA Pol II molecules at the initial stages of the transcription cycle."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]

Summary: Ubiquitin-like ligase-substrate adaptor activity (IEA). ARMC5 is the substrate receptor of a CUL3-RBX1 ligase: its BTB domain binds CUL3, and it recruits RPB1/Pol II and full-length SREBF for ubiquitination. Core function.

Reason: [PMID:35687106 "Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1."] [PMID:35862218 "We also found that ARMC5 interacted with CUL3 through its BTB domain and underwent self-ubiquitination."]