module: dmel_proteasome title: 26S proteasome in Drosophila melanogaster label: 26S proteasome module_type: PROTEIN_COMPLEX description: >- The 26S proteasome degrades proteins tagged with polyubiquitin chains. Its 20S core particle is a barrel of four stacked heptameric rings, two outer rings of alpha subunits that gate substrate entry and two inner rings of beta subunits, three of which (beta1, beta2 and beta5) are N-terminal threonine proteases with caspase-like, trypsin-like and chymotrypsin-like specificities. The 19S regulatory particle caps the core. Its base contains six AAA+ ATPases (Rpt1-Rpt6) that unfold substrates and open the core gate, together with the scaffolds Rpn1 and Rpn2. Ubiquitin receptors (Rpn10 and Rpn13) bind ubiquitylated substrates, the lid metalloprotease Rpn11 removes ubiquitin chains before degradation, and Uch-L5 bound to Rpn13 trims chains. Drosophila has a testis-specific 26S proteasome in which paralogs replace several alpha, beta, Rpt, Rpn and Uch-L5 subunits. summary: >- Ubiquitin-dependent ATP-driven protease formed by the 20S core particle and 19S regulatory particle, with a testis-specific paralog variant. concepts: - {id: GO:0000502, label: proteasome complex} parts: - id: core_particle label: 20S core particle role: proteolytic chamber concepts: - {id: GO:0005839, label: proteasome core complex} parts: - id: alpha_ring label: Alpha ring role: gated entry ring variant_sets: - id: alpha_ring_variants label: Somatic or testis alpha ring selection: ONE_OR_MORE variants: - id: alpha_ring_somatic label: Alpha ring (26S proteasome) genes: [Prosalpha1, Prosalpha1R, Prosalpha2, Prosalpha3, Prosalpha4, Prosalpha5, Prosalpha6, Prosalpha7] complex_term: {id: GO:0019773, label: "proteasome core complex, alpha-subunit complex"} - id: alpha_ring_testis label: Alpha ring (testis-specific 26S proteasome) genes: [Prosalpha1, Prosalpha1R, Prosalpha2, Prosalpha3T, Prosalpha4T1, Prosalpha4T2, Prosalpha5, Prosalpha6T, Prosalpha7] complex_term: {id: GO:0019773, label: "proteasome core complex, alpha-subunit complex"} - id: beta_ring label: Beta ring role: catalytic ring variant_sets: - id: beta_ring_variants label: Somatic or testis beta ring selection: ONE_OR_MORE variants: - id: beta_ring_somatic label: Beta ring (26S proteasome) genes: [Prosbeta1, Prosbeta2, Prosbeta3, Prosbeta4, Prosbeta5, Prosbeta6, Prosbeta7] complex_term: {id: GO:0019774, label: "proteasome core complex, beta-subunit complex"} unit_functions: Prosbeta1: {id: GO:0004298, label: threonine-type endopeptidase activity} Prosbeta2: {id: GO:0004298, label: threonine-type endopeptidase activity} Prosbeta5: {id: GO:0004298, label: threonine-type endopeptidase activity} - id: beta_ring_testis label: Beta ring (testis-specific 26S proteasome) genes: [Prosbeta1, Prosbeta2R1, Prosbeta2R2, Prosbeta3, Prosbeta4R1, Prosbeta4R2, Prosbeta5R1, Prosbeta5R2, Prosbeta6, Prosbeta7] complex_term: {id: GO:0019774, label: "proteasome core complex, beta-subunit complex"} unit_functions: Prosbeta1: {id: GO:0004298, label: threonine-type endopeptidase activity} - id: regulatory_particle label: 19S regulatory particle role: substrate recognition, deubiquitylation and unfolding concepts: - {id: GO:0022624, label: proteasome accessory complex} parts: - id: rp_base label: Regulatory particle base role: AAA+ ATPase ring and scaffolds variant_sets: - id: base_variants label: Somatic or testis base selection: ONE_OR_MORE variants: - id: base_somatic label: Base (26S proteasome) genes: [Rpt1, Rpt2, Rpt3, Rpt4, Rpt5, Rpt6, Rpn1, Rpn2] complex_term: {id: GO:0008540, label: "proteasome regulatory particle, base subcomplex"} unit_functions: Rpt1: {id: GO:0036402, label: proteasome-activating activity} Rpt2: {id: GO:0036402, label: proteasome-activating activity} Rpt3: {id: GO:0036402, label: proteasome-activating activity} Rpt4: {id: GO:0036402, label: proteasome-activating activity} Rpt5: {id: GO:0036402, label: proteasome-activating activity} Rpt6: {id: GO:0036402, label: proteasome-activating activity} - id: base_testis label: Base (testis-specific 26S proteasome) genes: [Rpt1, Rpt2, Rpt3R, Rpt4R, Rpt5, Rpt6R, Rpn1, Rpn2] complex_term: {id: GO:0008540, label: "proteasome regulatory particle, base subcomplex"} unit_functions: Rpt1: {id: GO:0036402, label: proteasome-activating activity} Rpt2: {id: GO:0036402, label: proteasome-activating activity} Rpt5: {id: GO:0036402, label: proteasome-activating activity} - id: rp_lid label: Regulatory particle lid role: deubiquitylating lid variant_sets: - id: lid_variants label: Rpn12 or Rpn12R lid selection: ONE_OR_MORE variants: - id: lid_somatic label: Lid (26S proteasome) genes: [Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, Rpn12] complex_term: {id: GO:0008541, label: "proteasome regulatory particle, lid subcomplex"} unit_functions: Rpn11: {id: GO:0140492, label: metal-dependent deubiquitinase activity} - id: lid_testis label: Lid (testis-specific 26S proteasome) genes: [Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, Rpn12R] complex_term: {id: GO:0008541, label: "proteasome regulatory particle, lid subcomplex"} unit_functions: Rpn11: {id: GO:0140492, label: metal-dependent deubiquitinase activity} - id: ubiquitin_receptors label: Ubiquitin receptors and Uch-L5 role: ubiquitin chain recognition and trimming variant_sets: - id: receptor_variants label: Somatic or testis receptor set selection: ONE_OR_MORE variants: - id: receptors_somatic label: Rpn10, Rpn13 and Uch-L5 genes: [Rpn10, Rpn13, Uch-L5] complex: false unit_functions: Uch-L5: {id: GO:0004843, label: cysteine-type deubiquitinase activity} - id: receptors_testis label: Rpn10, Rpn13R and Uch-L5R genes: [Rpn10, Rpn13R, Uch-L5R] complex: false connections: - {source: regulatory_particle, target: core_particle, connection_type: PROVIDES_INPUT_FOR, description: The regulatory particle unfolds deubiquitylated substrates and translocates them into the core particle.} notes: >- Somatic and testis-specific variants follow the FlyBase groups PSM26S and PSM26S-T; subunits shared by both appear in each variant. Prosalpha1R is a member of both FlyBase variant groups. The base, lid and ubiquitin-receptor split follows the conserved eukaryotic 19S organisation; Rpn10 and Rpn13 are modelled separately because their placement between base and lid is not sharply defined. Catalytic activity is asserted only for the canonical beta1 (Prosbeta1), beta2 (Prosbeta2) and beta5 (Prosbeta5) subunits; whether the testis paralogs Prosbeta2R1, Prosbeta2R2, Prosbeta5R1 and Prosbeta5R2 keep catalytic activity is not asserted. Likewise ATPase and deubiquitinase activities are not asserted for the testis paralogs Rpt3R, Rpt4R, Rpt6R and Uch-L5R.