ARMC8

Summary: Protein binding (IPI) with RMND5A, from the CTLH complex purification. RMND5A is the RING subunit of the same complex, and ARMC8's membership is captured by the GID complex row. Removed under the generic protein-binding policy; removal does not mean the interaction is false.

Reason: Removed under the generic protein-binding policy. The co-membership is real: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Protein binding (IPI) with TCF12, from the HI-II-14 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: Extracellular region (TAS, Reactome neutrophil degranulation). ARMC8 is listed among proteins released from neutrophil granules, based on granule proteomics. It has no characterized secretory role, and its CTLH function is intracellular; kept as non-core.

Reason: [file:reactome/R-HSA-6798745.md "Tertiary (gelatinase) granules are part of a continuum of peroxidase-negative"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Extracellular region (TAS, Reactome neutrophil degranulation). ARMC8 is listed among proteins released from neutrophil granules, based on granule proteomics. It has no characterized secretory role, and its CTLH function is intracellular; kept as non-core.

Reason: [file:reactome/R-HSA-6798749.md "Secondary (specific) granules are peroxidase-negative and rich in antimicrobial"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Nucleus (IDA). The CTLH complex, including ARMC8, is found in both nucleus and cytoplasm, and the Human Protein Atlas detects ARMC8 in the nucleoplasm. A nuclear pool is consistent with CTLH substrates such as transcription factors, though most of ARMC8 is cytoplasmic. Accepted.

Reason: [PMID:29911972 "Some of them, RanBP9 (Gid1), Rmnd5 (Gid2), Armc8 (Gid5), Twa1 (Gid8) and MAEA (GID9), have been found together in an ubiquitously expressed high-molecular weight assembly localized both to the nucleus and cytoplasm"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Nucleus (IEA). The CTLH complex, including ARMC8, is found in both nucleus and cytoplasm, and the Human Protein Atlas detects ARMC8 in the nucleoplasm. A nuclear pool is consistent with CTLH substrates such as transcription factors, though most of ARMC8 is cytoplasmic. Accepted.

Reason: [PMID:29911972 "Some of them, RanBP9 (Gid1), Rmnd5 (Gid2), Armc8 (Gid5), Twa1 (Gid8) and MAEA (GID9), have been found together in an ubiquitously expressed high-molecular weight assembly localized both to the nucleus and cytoplasm"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Nucleoplasm (IDA). The CTLH complex, including ARMC8, is found in both nucleus and cytoplasm, and the Human Protein Atlas detects ARMC8 in the nucleoplasm. A nuclear pool is consistent with CTLH substrates such as transcription factors, though most of ARMC8 is cytoplasmic. Accepted.

Reason: [PMID:29911972 "Some of them, RanBP9 (Gid1), Rmnd5 (Gid2), Armc8 (Gid5), Twa1 (Gid8) and MAEA (GID9), have been found together in an ubiquitously expressed high-molecular weight assembly localized both to the nucleus and cytoplasm"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Cytoplasm (IDA). The CTLH complex was purified from soluble HEK293 extract, ARMC8 is in the cytosol by antibody staining, and ARMC8alpha co-localizes with the endosomal sorting protein HRS. Core location.

Reason: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."] [PMID:20224683 "As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS."]

Summary: Cytoplasm (IEA). The CTLH complex was purified from soluble HEK293 extract, ARMC8 is in the cytosol by antibody staining, and ARMC8alpha co-localizes with the endosomal sorting protein HRS. Core location.

Reason: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."] [PMID:20224683 "As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS."]

Summary: Cytosol (IDA). The CTLH complex was purified from soluble HEK293 extract, ARMC8 is in the cytosol by antibody staining, and ARMC8alpha co-localizes with the endosomal sorting protein HRS. Core location.

Reason: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."] [PMID:20224683 "As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS."]

Summary: Cytosol (TAS, Reactome CTLH ubiquitination of LDHA). The CTLH complex, which includes ARMC8, ubiquitinates these cytosolic glycolytic enzymes; accepted.

Reason: [file:reactome/R-HSA-9861563.md "The CTLH complex consists of the proteins ARMC8, GID4, Muskelin,"] [file:reactome/R-HSA-9861563.md "The CTLH complex consists of the proteins ARMC8, GID4, Muskelin,"]

Summary: Cytosol (TAS, Reactome CTLH ubiquitination of PKM). The CTLH complex, which includes ARMC8, ubiquitinates these cytosolic glycolytic enzymes; accepted.

Reason: [file:reactome/R-HSA-9861640.md "(PKM2), inhibiting pyruvate kinase activity."] [file:reactome/R-HSA-9861563.md "The CTLH complex consists of the proteins ARMC8, GID4, Muskelin,"]

Summary: GID complex (IBA). ARMC8 alpha and beta are core subunits of the human CTLH complex, the mammalian GID E3 ligase. ARMC8 is part of its scaffold with RANBP9 and GID8, and its alpha isoform binds the substrate receptor GID4. Core location.

Reason: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."] [PMID:31285494 "We confirm that the complex immunoprecipitated from human cells comprises RanBPM, ARMC8 α/β, muskelin, WDR26, GID4 and the RING domain proteins RMND5A and MAEA."] [PMID:29911972 "To fill this gap, we initiated a series of systematic AP-MS experiments of HA-2xStrep (HSS) -tagged versions of the GID subunits Rmnd5a and Armc8 to examine the global interactome of the complex in HEK-293 cells."] [PMID:35682545 "In humans, the CTLH complex is named RanBP9 (also known as RanBPM; homologue of Gid1), GID8 (also known as TWA1; homologue of Gid8), and ARMC8 (similar to Gid5) act as the scaffold;"] [PMID:35682545 "An important difference, however, is that two ARMC8 isoforms (α and β), instead of one Gid5 in yeast, associate with the human complex [10,22,23], but only the α isoform can bind GID4 [20]."]

Summary: GID complex (NAS). ARMC8 alpha and beta are core subunits of the human CTLH complex, the mammalian GID E3 ligase. ARMC8 is part of its scaffold with RANBP9 and GID8, and its alpha isoform binds the substrate receptor GID4. Core location.

Reason: [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."] [PMID:31285494 "We confirm that the complex immunoprecipitated from human cells comprises RanBPM, ARMC8 α/β, muskelin, WDR26, GID4 and the RING domain proteins RMND5A and MAEA."] [PMID:29911972 "To fill this gap, we initiated a series of systematic AP-MS experiments of HA-2xStrep (HSS) -tagged versions of the GID subunits Rmnd5a and Armc8 to examine the global interactome of the complex in HEK-293 cells."] [PMID:35682545 "In humans, the CTLH complex is named RanBP9 (also known as RanBPM; homologue of Gid1), GID8 (also known as TWA1; homologue of Gid8), and ARMC8 (similar to Gid5) act as the scaffold;"] [PMID:35682545 "An important difference, however, is that two ARMC8 isoforms (α and β), instead of one Gid5 in yeast, associate with the human complex [10,22,23], but only the α isoform can bind GID4 [20]."]

Summary: Specific granule lumen (TAS, Reactome neutrophil degranulation). ARMC8 is listed among proteins released from neutrophil granules, based on granule proteomics. It has no characterized secretory role, and its CTLH function is intracellular; kept as non-core.

Reason: [file:reactome/R-HSA-6798749.md "Secondary (specific) granules are peroxidase-negative and rich in antimicrobial"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (IBA). The CTLH complex is an E3 ligase that ubiquitinates substrates for proteasomal degradation, including its own subunit muskelin. ARMC8 acts within it as a scaffold subunit, and ARMC8alpha also promotes proteasomal degradation of alpha-catenin. Accepted.

Reason: [PMID:31285494 "The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation."] [PMID:29911972 "Hpb1 protein turnover is regulated by the GID E3 ligase and biochemical evidence suggests that Hbp1 is directly ubiquitinated by the complex, which might contribute to the intermittent proliferation phenotype observed for GID-KO cell lines."] [PMID:35682545 "In humans, the CTLH complex is named RanBP9 (also known as RanBPM; homologue of Gid1), GID8 (also known as TWA1; homologue of Gid8), and ARMC8 (similar to Gid5) act as the scaffold;"] [PMID:18215130 "Proteasome-dependent degradation of alpha-catenin is regulated by interaction with ARMc8alpha."]

Summary: Proteasome-mediated ubiquitin-dependent protein catabolic process (NAS). The CTLH complex is an E3 ligase that ubiquitinates substrates for proteasomal degradation, including its own subunit muskelin. ARMC8 acts within it as a scaffold subunit, and ARMC8alpha also promotes proteasomal degradation of alpha-catenin. Accepted.

Reason: [PMID:31285494 "The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation."] [PMID:29911972 "Hpb1 protein turnover is regulated by the GID E3 ligase and biochemical evidence suggests that Hbp1 is directly ubiquitinated by the complex, which might contribute to the intermittent proliferation phenotype observed for GID-KO cell lines."] [PMID:35682545 "In humans, the CTLH complex is named RanBP9 (also known as RanBPM; homologue of Gid1), GID8 (also known as TWA1; homologue of Gid8), and ARMC8 (similar to Gid5) act as the scaffold;"] [PMID:18215130 "Proteasome-dependent degradation of alpha-catenin is regulated by interaction with ARMc8alpha."]

Summary: Tertiary granule lumen (TAS, Reactome neutrophil degranulation). ARMC8 is listed among proteins released from neutrophil granules, based on granule proteomics. It has no characterized secretory role, and its CTLH function is intracellular; kept as non-core.

Reason: [file:reactome/R-HSA-6798745.md "Tertiary (gelatinase) granules are part of a continuum of peroxidase-negative"] [PMID:17467196 "Here, we used tandem MS with an antibody against RanBPM to purify this complex from a soluble extract of HEK293 cells: we identified Muskelin, p48EMLP, p44CTLH, and the novel armadillo-repeat proteins ARMC8alpha and ARMC8beta as components."]

Summary: Ubiquitin protein ligase activity (NEW, IDA, contributes_to). The recombinant human GID/CTLH complex ubiquitinates the transcription factor HBP1 in vitro with UBE2H, and the complex controls HBP1 turnover in cells. The RING subunits RMND5A and MAEA carry the catalytic activity. ARMC8, a scaffold subunit and the AP-MS bait that defined the complex, contributes to it rather than having it alone.

Reason: [PMID:29911972 "To examine whether Hbp1 can be directly modified by the GID E3 ligase, we expressed and purified C-terminally tagged Hbp1 from Sf9 insect cells and performed in vitro ubiquitination assays in the presence of recombinant GID complex and Ube2H (Figure 5—figure supplement 1F)."] [PMID:29911972 "Hpb1 protein turnover is regulated by the GID E3 ligase and biochemical evidence suggests that Hbp1 is directly ubiquitinated by the complex, which might contribute to the intermittent proliferation phenotype observed for GID-KO cell lines."] [PMID:35682545 "In humans, the CTLH complex is named RanBP9 (also known as RanBPM; homologue of Gid1), GID8 (also known as TWA1; homologue of Gid8), and ARMC8 (similar to Gid5) act as the scaffold;"]