BioPAX pathway converted from "Autodegradation of Cdh1 by Cdh1:APC/C" in the Reactome database.Autodegradation of Cdh1 by Cdh1:APC/C Cdh1 is degraded by the APC/C during in G1 and G0. This auto-regulation may contribute to reducing the levels of Cdh1 levels during G1 and G0 (Listovsky et al., 2004).Authored: Lorca, T, Castro, A, 2006-01-26 00:00:00Reviewed: Peters, JM, 2006-03-27 22:55:09Edited: Matthews, L, 2006-01-30 00:00:00LEFT-TO-RIGHT6.3.2.19Multiubiquitination of APC/C-associated Cdh1Cdh1 is multiubiquitinated by the APC/C:Cdh1 complex prior to degradation by the 26S proteasome.Authored: Lorca, T, Castro, A, 2006-01-26 00:00:00Reviewed: Peters, JM, 2006-03-27 22:55:09Edited: Matthews, L, 2006-02-17 05:21:42phospho-Cdh1:phospho-APC/C complexReactome DB_ID: 174167nucleoplasmGENE ONTOLOGYGO:0005654phosphorylated anaphase promoting complex (APC/C)Reactome DB_ID: 174109ANAPC10Apc10/Doc1Reactome DB_ID: 174047UniProt:Q9UM13 ANAPC10ANAPC10APC10FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:25043029). The C-terminus of APC10 binds to CDC27/APC3 (PubMed:11524682). Interacts with PIWIL1; interaction only takes place when PIWIL1 binds piRNA (By similarity).SIMILARITY Belongs to the APC10 family.Homo sapiensNCBI Taxonomy9606UniProtQ9UM131EQUAL185EQUALReactome Database ID Release 71174047Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174047ReactomeR-HSA-1740471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174047.1Reactomehttp://www.reactome.org1UbcXUBE2CUbcH10E2-CReactome DB_ID: 174188UniProt:O00762 UBE2CUBE2CUBCH10FUNCTION Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of the APC/C complex, composed of at least 14 distinct subunits that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa. Within this complex, directly interacts with ANAPC2.PTM Autoubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Its degradation plays a central role in APC/C regulation, allowing cyclin-A accumulation before S phase entry. APC/C substrates inhibit the autoubiquitination of UBE2C/UBCH10 but not its E2 function, hence APC/C remaining active until its substrates have been destroyed.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family.UniProtO007622EQUAL179EQUALReactome Database ID Release 71174188Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174188ReactomeR-HSA-1741881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174188.11ANAPC15Anaphase-promoting complex subunit 15APC15_HUMANReactome DB_ID: 6805136UniProt:P60006 ANAPC15ANAPC15C11orf51HSPC020FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. In the complex, plays a role in the release of the mitotic checkpoint complex (MCC) from the APC/C: not required for APC/C activity itself, but promotes the turnover of CDC20 and MCC on the APC/C, thereby participating in the responsiveness of the spindle assembly checkpoint. Also required for degradation of CDC20.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.SIMILARITY Belongs to the APC15 family.UniProtP600061EQUAL121EQUALReactome Database ID Release 716805136Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6805136ReactomeR-HSA-68051361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6805136.11ANAPC16Anaphase-promoting complex subunit 16APC16_HUMANReactome DB_ID: 6805137UniProt:Q96DE5 ANAPC16ANAPC16C10orf104CENP-27FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:25043029). ANAPC16 associates with the rest of the complex independently of ANAPC2 and ANAPC11.SIMILARITY Belongs to the APC16 family.UniProtQ96DE52EQUAL110EQUALReactome Database ID Release 716805137Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6805137ReactomeR-HSA-68051371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6805137.11Apc5ANAPC5Reactome DB_ID: 174153UniProt:Q9UJX4 ANAPC5ANAPC5APC5FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.DOMAIN The TPR repeats are six to seven residues longer than a canonical TPR motif.SIMILARITY Belongs to the APC5 family.UniProtQ9UJX41EQUAL755EQUALReactome Database ID Release 71174153Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174153ReactomeR-HSA-1741531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174153.11Apc2ANAPC2Reactome DB_ID: 174141UniProt:Q9UJX6 ANAPC2ANAPC2APC2KIAA1406FUNCTION Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:25043029, PubMed:26083744). In the context of the APC/C complex, directly interacts with UBE2C and UBE2S (PubMed:27259151). Interacts (via cullin domain) with ANAPC11 and with UBCH10 (PubMed:11739784). Interacts with NEUROD2 (By similarity).SIMILARITY Belongs to the cullin family.UniProtQ9UJX61EQUAL822EQUALReactome Database ID Release 71174141Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174141ReactomeR-HSA-1741411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174141.11Apc4ANAPC4Reactome DB_ID: 174115UniProt:Q9UJX5 ANAPC4ANAPC4APC4FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:25043029, PubMed:27259151, PubMed:9469815, PubMed:26083744). In the context of the APC/C complex, directly interacts with UBE2S (PubMed:27259151).SIMILARITY Belongs to the APC4 family.UniProtQ9UJX51EQUAL808EQUALReactome Database ID Release 71174115Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174115ReactomeR-HSA-1741151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174115.11Apc7ANAPC7Reactome DB_ID: 174204UniProt:Q9UJX3 ANAPC7ANAPC7APC7FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT V-shaped homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:25043029, PubMed:26083744).SIMILARITY Belongs to the APC7 family.CAUTION It is uncertain whether Met-1 or Met-35 is the initiator.UniProtQ9UJX31EQUAL599EQUALReactome Database ID Release 71174204Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174204ReactomeR-HSA-1742041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174204.11E1UBE2E1Reactome DB_ID: 174063UniProt:P51965 UBE2E1UBE2E1UBCH6FUNCTION Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes the covalent attachment of ISG15 to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. In vitro also catalyzes 'Lys-48'-linked polyubiquitination.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with RNF14.PTM ISGylation suppresses ubiquitin E2 enzyme activity.PTM Autoubiquitinated in vitro.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family.UniProtP519652EQUAL193EQUALReactome Database ID Release 71174063Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174063ReactomeR-HSA-1740631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174063.11UBE2D1UbcH5/Ubc4Reactome DB_ID: 174197UniProt:P51668 UBE2D1UBE2D1SFTUBC5AUBCH5UBCH5AFUNCTION Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:22496338). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:20061386). Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1 (PubMed:18042044, PubMed:18359941). Ubiquitinates STUB1-associated HSP90AB1 in vitro (PubMed:18042044). Lacks inherent specificity for any particular lysine residue of ubiquitin (PubMed:18042044). Essential for viral activation of IRF3 (PubMed:19854139). Mediates polyubiquitination of CYP3A4 (PubMed:19103148).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with RNF11.TISSUE SPECIFICITY Ubiquitous. Up-regulated in livers of iron-overloaded patients with hereditary hemochromatosis.PTM Autoubiquitinated in vitro.SIMILARITY Belongs to the ubiquitin-conjugating enzyme family.CAUTION PubMed:9362508 cloned and sequenced SFT which consisted of UBE2D1 last coding exon along with intronic sequences on the 5'-end of this exon. A function in iron transport has been described.UniProtP516681EQUAL147EQUALReactome Database ID Release 71174197Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174197ReactomeR-HSA-1741971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174197.11CDC23Apc8/Cdc23Reactome DB_ID: 174228UniProt:Q9UJX2 CDC23CDC23ANAPC8FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.PTM Phosphorylated. Phosphorylation on Thr-562 occurs specifically during mitosis.SIMILARITY Belongs to the APC8/CDC23 family.UniProtQ9UJX21EQUAL597EQUALReactome Database ID Release 71174228Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174228ReactomeR-HSA-1742281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174228.11CDC27Apc3/Cdc27Reactome DB_ID: 174175UniProt:P30260 CDC27CDC27ANAPC3D0S1430ED17S978EFUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:25043029). Interacts with RB. Interacts with FAM168B/MANI (By similarity). Interacts with MCPH1 (PubMed:22139841).PTM Phosphorylated. Phosphorylation on Ser-426 and Thr-446 occurs specifically during mitosis.SIMILARITY Belongs to the APC3/CDC27 family.UniProtP302601EQUAL824EQUALReactome Database ID Release 71174175Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174175ReactomeR-HSA-1741751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174175.11CDC26Cdc26Reactome DB_ID: 174216UniProt:Q8NHZ8 CDC26CDC26ANAPC12C9orf17FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex.PATHWAY Protein modification; protein ubiquitination.SUBUNIT V-shaped homodimer. Interacts with CDC16. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.SIMILARITY Belongs to the CDC26 family.UniProtQ8NHZ81EQUAL85EQUALReactome Database ID Release 71174216Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174216ReactomeR-HSA-1742161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174216.11CDC16Apc6/Cdc16Reactome DB_ID: 174049UniProt:Q13042 CDC16CDC16ANAPC6FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT V-shaped homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:25043029). Interacts with PPP5C and CDC20 (PubMed:9628895, PubMed:9405394). Interacts with CDC26 (PubMed:19668213).DOMAIN TPR repeats 1-7 mediate homodimerization, while the C-terminal TPR repeats bind to CDC26, burying its hydrophobic N-terminus.PTM Phosphorylated. Phosphorylation on Ser-560 occurs specifically during mitosis.SIMILARITY Belongs to the APC6/CDC16 family.UniProtQ130421EQUAL620EQUALReactome Database ID Release 71174049Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174049ReactomeR-HSA-1740491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174049.11ANAPC1Apc1/Tsg24Reactome DB_ID: 174217UniProt:Q9H1A4 ANAPC1ANAPC1TSG24FUNCTION Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.PTM Phosphorylated. Phosphorylation on Ser-355 occurs specifically during mitosis.SIMILARITY Belongs to the APC1 family.UniProtQ9H1A41EQUAL1944EQUALReactome Database ID Release 71174217Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174217ReactomeR-HSA-1742171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174217.11Apc11ANAPC11Reactome DB_ID: 174163UniProt:Q9NYG5 ANAPC11ANAPC11HSPC214FUNCTION Together with the cullin protein ANAPC2, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex.PATHWAY Protein modification; protein ubiquitination.SUBUNIT The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:10922056, PubMed:25043029). Interacts with the cullin domain of ANAPC2 (PubMed:11739784). Interacts with UBE2D2 (PubMed:11739784).TISSUE SPECIFICITY Expressed at high levels in skeletal muscle and heart; in moderate levels in brain, kidney, and liver; and at low levels in colon, thymus, spleen, small intestine, placenta, lung and peripheral blood leukocyte.DOMAIN The RING-type zinc finger domain coordinates an additional third zinc ion.PTM Auto-ubiquitinated.SIMILARITY Belongs to the RING-box family.UniProtQ9NYG51EQUAL84EQUALReactome Database ID Release 71174163Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174163ReactomeR-HSA-1741631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174163.11Reactome Database ID Release 71174109Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174109ReactomeR-HSA-1741092Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174109.21p-FZR1phospho-Cdh1Reactome DB_ID: 174257UniProt:Q9UM11 FZR1FZR1CDH1FYRFZRKIAA1242FUNCTION Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:25349192).PATHWAY Protein modification; protein ubiquitination.SUBUNIT The unphosphorylated form interacts with APC/C during mitosis (PubMed:26083744, PubMed:9734353). Interacts with NINL (PubMed:17403670). Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (PubMed:11459825, PubMed:11459826). Interacts with SIRT2 and USP37 (PubMed:21596315, PubMed:22014574). Interacts (via WD repeats) with MAK (PubMed:21986944). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (PubMed:25349192). Interacts with HECW2 (PubMed:24163370).TISSUE SPECIFICITY Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines whereas isoform 3 is expressed only at low levels in these tissues.PTM Acetylated. Deacetylated by SIRT2 at Lys-69 and Lys-159; deacetylation enhances the interaction of FZR1 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).PTM Phosphorylated during mitosis, probably by maturation promoting factor (MPF), leading to its dissociation of the APC/C. Following DNA damage, it is dephosphorylated by CDC14B in G2 phase, leading to its reassociation with the APC/C, and allowing an efficient G2 DNA damage checkpoint. Phosphorylated by MAK.SIMILARITY Belongs to the WD repeat CDC20/Fizzy family.UniProtQ9UM11phosphorylated residueMODMOD:006961EQUAL496EQUALReactome Database ID Release 71174257Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174257ReactomeR-HSA-1742571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174257.11Reactome Database ID Release 71174167Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174167ReactomeR-HSA-1741671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174167.1Converted from EntitySet in ReactomeUbUbiquitinUBIQ_HUMANReactome DB_ID: 68524RPS27A(1-76)ubiquitin (RPS27A)Reactome DB_ID: 939849UniProt:P62979 RPS27ARPS27AUBA80UBCEP1FUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.FUNCTION 40S Ribosomal protein S27a: Component of the 40S subunit of the ribosome.SUBUNIT Ribosomal protein S27a is part of the 40S ribosomal subunit.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.UniProtP629791EQUAL76EQUALReactome Database ID Release 71939849Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939849ReactomeR-HSA-9398491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939849.1UBA52(1-76)ubiquitin (UBA52)Reactome DB_ID: 939844UniProt:P62987 UBA52UBA52UBCEP2FUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.FUNCTION 60S ribosomal protein L40: Component of the 60S subunit of the ribosome. Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs.SUBUNIT Ribosomal protein L40 is part of the 60S ribosomal subunit. Interacts with UBQLN1 (via UBA domain).PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.UniProtP629871EQUAL76EQUALReactome Database ID Release 71939844Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939844ReactomeR-HSA-9398441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939844.1UBBUBB(1-76)ubiquitin (UBB 1)Reactome DB_ID: 939847UniProt:P0CG47 UBBUBBFUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS The mRNA encoding variant UBB(+1) is produced by an unknown mechanism involving the deletion of a GT dinucleotide in the close proximity of a GAGAG motif (PubMed:9422699). This variant mRNA is found in normal brain, but the encoded protein accumulates only in brain neurofibrillary tangles and neuritic plaques in Alzheimer disease and other tauopathies, as well as polyglutaminopathies (PubMed:14597671). UBB(+1) variant cannot be used for polyubiquitination, is not effectively degraded by the proteasome when ubiquitinated and ubiquitinated UBB(+1) is refractory to disassembly by deubiquitinating enzymes (DUBs). In healthy brain, UBB(+1) C-terminus can be cleaved by UCHL3 (PubMed:21762696).MISCELLANEOUS For a better understanding, features related to ubiquitin are only indicated for the first chain.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG471EQUAL76EQUALReactome Database ID Release 71939847Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939847ReactomeR-HSA-9398471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939847.1UBB(77-152)ubiquitin (UBB 2)Reactome DB_ID: 93987077EQUAL152EQUALReactome Database ID Release 71939870Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939870ReactomeR-HSA-9398701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939870.1UBB(153-228)ubiquitin (UBB 3)Reactome DB_ID: 939854153EQUAL228EQUALReactome Database ID Release 71939854Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939854ReactomeR-HSA-9398541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939854.1UBCUBC(1-76)ubiquitin (UBC 1)Reactome DB_ID: 939871UniProt:P0CG48 UBCUBCFUNCTION Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.PTM Ubiquitin: Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30 (PubMed:25527291).PTM Ubiquitin: Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG481EQUAL76EQUALReactome Database ID Release 71939871Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939871ReactomeR-HSA-9398711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939871.1UBC(77-152)ubiquitin (UBC 2)Reactome DB_ID: 93986977EQUAL152EQUALReactome Database ID Release 71939869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939869ReactomeR-HSA-9398691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939869.1UBC(153-228)ubiquitin (UBC 3)Reactome DB_ID: 939853153EQUAL228EQUALReactome Database ID Release 71939853Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939853ReactomeR-HSA-9398531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939853.1UBC(229-304)ubiquitin (UBC 4)Reactome DB_ID: 939857229EQUAL304EQUALReactome Database ID Release 71939857Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939857ReactomeR-HSA-9398571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939857.1UBC(305-380)ubiquitin (UBC 5)Reactome DB_ID: 939863305EQUAL380EQUALReactome Database ID Release 71939863Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939863ReactomeR-HSA-9398631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939863.1UBC(381-456)ubiquitin (UBC 6)Reactome DB_ID: 939856381EQUAL456EQUALReactome Database ID Release 71939856Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939856ReactomeR-HSA-9398561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939856.1UBC(457-532)ubiquitin (UBC 7)Reactome DB_ID: 939862457EQUAL532EQUALReactome Database ID Release 71939862Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939862ReactomeR-HSA-9398621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939862.1UBC(533-608)ubiquitin (UBC 8)Reactome DB_ID: 939866533EQUAL608EQUALReactome Database ID Release 71939866Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939866ReactomeR-HSA-9398661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939866.1UBC(609-684)ubiquitin (UBC 9)Reactome DB_ID: 939868609EQUAL684EQUALReactome Database ID Release 71939868Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939868ReactomeR-HSA-9398681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-939868.1Reactome Database ID Release 7168524Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68524ReactomeR-HSA-685243Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-68524.33multiubiquitinated Cdh1 associated with APC/CReactome DB_ID: 1740683phospho-Cdh1:phospho-APC/CReactome DB_ID: 17421311Reactome Database ID Release 71174213Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174213ReactomeR-HSA-1742131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174213.11Reactome Database ID Release 71174068Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174068ReactomeR-HSA-1740681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174068.1ACTIVATIONactiveUnit: #Complex2GENE ONTOLOGYGO:0004842gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 71174085Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174085Reactome Database ID Release 71174057Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174057ReactomeR-HSA-1740572Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174057.215029244Pubmed2004Mammalian Cdh1/Fzr mediates its own degradationListovsky, TOren, YSYudkovsky, YMahbubani, HMWeiss, AMLebendiker, MBrandeis, MEMBO J 23:1619-26GENE ONTOLOGYGO:0006511gene ontology term for cellular processMIMI:0359LEFT-TO-RIGHTDegradation of multiubiquitinated Cdh1At the beginning of this reaction, 1 molecule of 'multiubiquitinated Cdh1 associated with APC/C' is present. At the end of this reaction, 1 molecule of 'phosphorylated anaphase promoting complex (APC/C)', and 3 molecules of 'ubiquitin' are present.<br><br> This reaction takes place in the 'nucleoplasm' and is mediated by the 'endopeptidase activity' of '26S proteasome'.<br>Authored: Matthews, L, 2006-01-30 00:00:00Reviewed: Peters, JM, 2006-03-27 22:55:09Edited: Matthews, L, 2006-01-30 00:00:003ACTIVATION26S proteasomeReactome DB_ID: 177750PSMC126S protease regulatory subunit 4P26s4Reactome DB_ID: 174338UniProt:P62191 PSMC1PSMC1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC1 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC1 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with SCA7 (PubMed:11734547). Interacts with NGLY1 (PubMed:15358861). Interacts with PAAF1 (PubMed:15831487).SIMILARITY Belongs to the AAA ATPase family.UniProtP621912EQUAL440EQUALReactome Database ID Release 71174338Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174338ReactomeR-HSA-1743381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174338.11PSMD1226S proteasome non-ATPase regulatory subunit 1226S proteasome regulatory subunit p55Reactome DB_ID: 174339UniProt:O00232 PSMD12PSMD12FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex (PubMed:27428775,PubMed:27342858). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (PubMed:27428775,PubMed:27342858). The regulatory particle is made of a lid composed of 9 subunits including PSMD12, a base containing 6 ATPases and few additional components (PubMed:27428775,PubMed:27342858). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the proteasome subunit p55 family.UniProtO002322EQUAL456EQUALReactome Database ID Release 71174339Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174339ReactomeR-HSA-1743391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174339.11PSMD926S proteasome non-ATPase regulatory subunit 926S proteasome regulatory subunit p27Reactome DB_ID: 174321UniProt:O00233 PSMD9PSMD9FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex assembly is part of an intermediate PSMD9:PSMC6:PSMC3 module, also known as modulator trimer complex; PSMD9 is released during the further base assembly process.SUBUNIT Interacts with PSMC3. Part of a transient complex (modulator) containing PSMD9, PSMC6 and PSMC3 formed during the assembly of the 26S proteasome.TISSUE SPECIFICITY Expressed in all tissues tested, highly expressed in liver and kidney.SIMILARITY Belongs to the proteasome subunit p27 family.CAUTION Was initially identified as a component of the 26S proteasome.UniProtO002331EQUAL223EQUALReactome Database ID Release 71174321Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174321ReactomeR-HSA-1743211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174321.11HSN3PSMB4Proteasome subunit beta type 4Proteasome subunit beta type 4 precursor Proteasome beta chainMacropain beta chainMulticatalytic endopeptidase complex beta chainProteasome chain 3HsBPROS26Reactome DB_ID: 174343UniProt:P28070 PSMB4PSMB4PROS26FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Forms a ternary complex with SMAD1 and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Interacts with PRPF19 (PubMed:11571290, PubMed:12097147).SUBUNIT (Microbial infection) Interacts with HTLV-1 Tax protein.SUBUNIT (Microbial infection) Interacts with HIV-1 Nef and Tat proteins.INDUCTION Up-regulated in fibrolamellar carcinomas.SIMILARITY Belongs to the peptidase T1B family.CAUTION A report observed N-glycosylation at Asn-83 (PubMed:19139490). However, as the protein does not localize in an extracellular compartment of the cell, additional evidence is required to confirm this result.UniProtP2807046EQUAL264EQUALReactome Database ID Release 71174343Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174343ReactomeR-HSA-1743431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174343.11PSMA2Proteasome subunit alpha type 2 Proteasome component C3Macropain subunit C3Multicatalytic endopeptidase complex subunit C3Reactome DB_ID: 174345UniProt:P25787 PSMA2PSMA2HC3PSC3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.INDUCTION Down-regulated by antioxidants BO-653 and probucol. Down-regulated in response to enterovirus 71 (EV71) infection (at protein level).PTM Phosphorylated on tyrosine residues; which may be important for nuclear import.SIMILARITY Belongs to the peptidase T1A family.UniProtP257872EQUAL234EQUALReactome Database ID Release 71174345Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174345ReactomeR-HSA-1743451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174345.11PSMB10Proteasome subunit beta type 10Proteasome subunit beta type 10 precursor Proteasome MECl-1Macropain subunit MECl-1Multicatalytic endopeptidase complex subunit MECl-1Reactome DB_ID: 174349UniProt:P40306 PSMB10PSMB10LMP10MECL1FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB7. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by IFNG/IFN-gamma (at protein level). Up-regulated by IRF1. Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Up-regulated by CD40L via the NFKB1 pathway in cancer cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.SIMILARITY Belongs to the peptidase T1B family.UniProtP4030640EQUAL273EQUALReactome Database ID Release 71174349Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174349ReactomeR-HSA-1743491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174349.11PSMC5Probable 26S protease regulatory subunit 8Reactome DB_ID: 174312UniProt:P62195 PSMC5PSMC5SUG1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC5 and few additional components (PubMed:27428775, PubMed:27342858). Component of a complex with USP49 and RUVBL1 (PubMed:23824326). Interacts with PRPF19. Interacts with TRIM5 (PubMed:22078707). Interacts with NDC80 (PubMed:9295362, PubMed:10409732). Interacts with PAAF1 (PubMed:15831487). Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR) (By similarity). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the AAA ATPase family.UniProtP621952EQUAL406EQUALReactome Database ID Release 71174312Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174312ReactomeR-HSA-1743121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174312.11PSMA1Proteasome subunit alpha type 1 Proteasome component C2Macropain subunit C2Multicatalytic endopeptidase complex subunit C2Proteasome nu chain30 kDa prosomal proteinPROS-30Reactome DB_ID: 174333UniProt:P25786 PSMA1PSMA1HC2NUPROS30PSC2FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with NOTCH3. Interacts with ZFAND1 (PubMed:29804830).INDUCTION Induced in breast cancer tissue (at protein level). Up-regulated in liver tumor tissues.SIMILARITY Belongs to the peptidase T1A family.UniProtP257861EQUAL263EQUALReactome Database ID Release 71174333Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174333ReactomeR-HSA-1743331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174333.11PSMA4Proteasome subunit alpha type 4 Proteasome component C9Macropain subunit C9Multicatalytic endopeptidase complex subunit C9Proteasome subunit LReactome DB_ID: 174324UniProt:P25789 PSMA4PSMA4HC9PSC9FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interaction with HTLV-1 TAX protein favors NFKB1 activation.INDUCTION Down-regulated by antioxidants BO-653 and probucol.SIMILARITY Belongs to the peptidase T1A family.UniProtP257891EQUAL261EQUALReactome Database ID Release 71174324Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174324ReactomeR-HSA-1743241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174324.11PSMB1Proteasome subunit beta type 1 Proteasome component C5Macropain subunit C5Multicatalytic endopeptidase complex subunit C5Proteasome gamma chainReactome DB_ID: 174347UniProt:P20618 PSMB1PSMB1PSC5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with SERPINB2. Interacts with RFPL4A (By similarity).SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.SIMILARITY Belongs to the peptidase T1B family.UniProtP2061829EQUAL241EQUALReactome Database ID Release 71174347Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174347ReactomeR-HSA-1743471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174347.11PSMB6Proteasome subunit beta type 6Proteasome subunit beta type 6 precursor Proteasome delta chainMacropain delta chainMulticatalytic endopeptidase complex delta chainProteasome subunit YReactome DB_ID: 174342UniProt:P28072 PSMB6PSMB6LMPYYFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolizing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.INDUCTION Down-regulated by IFNG/IFN-gamma (at protein level). Up-regulated in anaplastic thyroid cancer cell lines.SIMILARITY Belongs to the peptidase T1B family.UniProtP2807235EQUAL239EQUALReactome Database ID Release 71174342Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174342ReactomeR-HSA-1743421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174342.11PSMD1126S proteasome non-ATPase regulatory subunit 1126S proteasome regulatory subunit S926S proteasome regulatory subunit p44.5Reactome DB_ID: 174327UniProt:O00231 PSMD11PSMD11FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD11, a base containing 6 ATPases and few additional components.TISSUE SPECIFICITY Highly expressed in embryonic stem cells (ESCs). Expression decreases as ESCs differentiate.INDUCTION By FOXO4; expression in embryonic stem cells (ESCs) is mediated by FOXO4.PTM Phosphorylated by AMPK.SIMILARITY Belongs to the proteasome subunit S9 family.UniProtO002312EQUAL422EQUALReactome Database ID Release 71174327Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174327ReactomeR-HSA-1743271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174327.11PSMD326S proteasome non-ATPase regulatory subunit 326S proteasome regulatory subunit S3Proteasome subunit p58Reactome DB_ID: 174328UniProt:O43242 PSMD3PSMD3FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD3, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878). Interacts with ERCC6 (PubMed:26030138).SIMILARITY Belongs to the proteasome subunit S3 family.UniProtO432421EQUAL534EQUALReactome Database ID Release 71174328Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174328ReactomeR-HSA-1743281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174328.11PSMB3Proteasome subunit beta type 3 Proteasome theta chainProteasome chain 13Proteasome component C10-IIReactome DB_ID: 174341UniProt:P49720 PSMB3PSMB3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.INDUCTION Up-regulated in asthenozoospermic sperm.SIMILARITY Belongs to the peptidase T1B family.UniProtP497202EQUAL205EQUALReactome Database ID Release 71174341Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174341ReactomeR-HSA-1743411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174341.11PSMD226S proteasome non-ATPase regulatory subunit 226S proteasome regulatory subunit S226S proteasome subunit p97Tumor necrosis factor type 1 receptor associated protein 255.11 proteinReactome DB_ID: 174311UniProt:Q13200 PSMD2PSMD2TRAP2FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.FUNCTION Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD2 (PubMed:27428775, PubMed:27342858). Interacts with RPGRIP1L (By similarity). Interacts with CRY1 in a KDM8-dependent manner (By similarity).TISSUE SPECIFICITY Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta.SIMILARITY Belongs to the proteasome subunit S2 family.UniProtQ132001EQUAL908EQUALReactome Database ID Release 71174311Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174311ReactomeR-HSA-1743111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174311.11PSMC326S protease regulatory subunit 6ATAT-binding protein 1TBP-1Proteasome subunit P50Reactome DB_ID: 174313UniProt:P17980 PSMC3PSMC3TBP1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC3 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with PAAF1 (PubMed:15831487).SUBUNIT (Microbial infection) Interacts with HIV-1 Tat.PTM Sumoylated by UBE2I in response to MEKK1-mediated stimuli.SIMILARITY Belongs to the AAA ATPase family.UniProtP179801EQUAL439EQUALReactome Database ID Release 71174313Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174313ReactomeR-HSA-1743131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174313.11PSMD1326S proteasome non-ATPase regulatory subunit 1326S proteasome regulatory subunit S1126S proteasome regulatory subunit p40.5Reactome DB_ID: 174326UniProt:Q9UNM6 PSMD13PSMD13FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD13, a base containing 6 ATPases and few additional components.SIMILARITY Belongs to the proteasome subunit S11 family.UniProtQ9UNM61EQUAL376EQUALReactome Database ID Release 71174326Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174326ReactomeR-HSA-1743261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174326.11p31PSMD826S proteasome non-ATPase regulatory subunit 826S proteasome regulatory subunit S14Reactome DB_ID: 174318UniProt:P48556 PSMD8PSMD8FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD8, a base containing 6 ATPases and few additional components. Interacts with DDI2 (PubMed:29290612).SIMILARITY Belongs to the proteasome subunit S14 family.CAUTION It is uncertain whether Met-1 or Met-64 is the initiator.UniProtP485561EQUAL350EQUALReactome Database ID Release 71174318Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174318ReactomeR-HSA-1743181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174318.11p42APSMD626S proteasome non-ATPase regulatory subunit 626S proteasome regulatory subunit S10Proteasome regulatory particle subunit p44S10Reactome DB_ID: 174316UniProt:Q15008 PSMD6PSMD6KIAA0107PFAAP4FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD6, a base containing 6 ATPases and few additional components.SIMILARITY Belongs to the proteasome subunit S10 family.UniProtQ150081EQUAL389EQUALReactome Database ID Release 71174316Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174316ReactomeR-HSA-1743161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174316.11PSME1Proteasome activator complex subunit 1Proteasome activator 28-alpha subunitPA28alphaPA28aActivator of multicatalytic protease subunit 111S regulator complex alpha subunitREG-alphaInterferon gamma up-regulated I-5111 proteinIGUP I-5111Reactome DB_ID: 174320UniProt:Q06323 PSME1PSME1IFI5111FUNCTION Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.SUBUNIT Heterodimer of PSME1 and PSME2, which forms a hexameric ring. PSME1 can form homoheptamers.INDUCTION By IFNG/IFN-gamma.SIMILARITY Belongs to the PA28 family.UniProtQ063231EQUAL249EQUALReactome Database ID Release 71174320Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174320ReactomeR-HSA-1743201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174320.11PSME3Proteasome activator complex subunit 3Proteasome activator 28-gamma subunitPA28gammaPA28gActivator of multicatalytic protease subunit 311S regulator complex gamma subunitREG-gammaKi nuclear autoantigenReactome DB_ID: 174310UniProt:P61289 PSME3PSME3FUNCTION Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).SUBUNIT Homoheptamer; the stability of the heptamer is essential for the specific activation of the trypsine-like subunit and inhibition of the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits of the proteasome. Interacts with p53/TP53 and MDM2. Interacts with MAP3K3 (By similarity). Associates with the proteasome. Interacts with CCAR2. Interacts with FAM192A (via C-terminus); the interaction is direct and promotes the association of PSME3 with the 20S proteasome (PubMed:29934401). Interacts with COIL; the interaction is inhibited by FAM192A (PubMed:29934401).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus UL27.INDUCTION Up-regulated in thyroid carcinoma cells.DOMAIN The C-terminal sequences affect heptamer stability and proteasome affinity.PTM Phosphorylated by MAP3K3 (By similarity). Phosphorylation at Ser-247 promotes its association with CCAR2.PTM Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1.SIMILARITY Belongs to the PA28 family.UniProtP612892EQUAL254EQUALReactome Database ID Release 71174310Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174310ReactomeR-HSA-1743101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174310.11p27KPSMA6Proteasome subunit alpha type 6 Proteasome iota chainMacropain iota chainMulticatalytic endopeptidase complex iota chain27 kDa prosomal proteinPROS-27Reactome DB_ID: 174314UniProt:P60900 PSMA6PSMA6PROS27FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with ALKBH4 (PubMed:23145062).SIMILARITY Belongs to the peptidase T1A family.UniProtP609001EQUAL246EQUALReactome Database ID Release 71174314Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174314ReactomeR-HSA-1743141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174314.11PSMB7Proteasome subunit beta type 7Proteasome subunit beta type 7 precursor Proteasome subunit ZMacropain chain ZMulticatalytic endopeptidase complex chain ZReactome DB_ID: 174331UniProt:Q99436 PSMB7PSMB7ZFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 Tat protein.TISSUE SPECIFICITY Expressed at a low level in colonic mucosa. Up-regulated in colorectal cancer tissues.SIMILARITY Belongs to the peptidase T1B family.UniProtQ9943644EQUAL277EQUALReactome Database ID Release 71174331Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174331ReactomeR-HSA-1743311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174331.11PSMB8Proteasome subunit beta type 8Proteasome subunit beta type 8 precursor Proteasome component C13Macropain subunit C13Multicatalytic endopeptidase complex subunit C13Reactome DB_ID: 174336UniProt:P28062 PSMB8PSMB8LMP7PSMB5iRING10Y2FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up-regulated by heat shock treatment.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.SIMILARITY Belongs to the peptidase T1B family.UniProtP2806273EQUAL276EQUALReactome Database ID Release 71174336Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174336ReactomeR-HSA-1743361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174336.11PSMB9Proteasome subunit beta type 9Proteasome subunit beta type 9 precursor Proteasome chain 7Macropain chain 7Multicatalytic endopeptidase complex chain 7RING12 proteinLow molecular mass protein 2Reactome DB_ID: 174334UniProt:P28065 PSMB9PSMB9LMP2PSMB6iRING12FUNCTION The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.DEVELOPMENTAL STAGE Highly expressed in immature dendritic cells (at protein level).INDUCTION Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by tumor necrosis factor-alpha (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Up-regulated by heat shock treatment. Up-regulated by CD40L via the NFKB1 pathway in cancer cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.MISCELLANEOUS Encoded in the MHC class II region.MISCELLANEOUS A model for self-activation in which residue Thr-21 serves as nucleophile and Lys-53 as proton donor/acceptor has been proposed. Subunit processing of mammalian beta-subunits proceeds via a novel ordered two-step mechanism involving autocatalysis.SIMILARITY Belongs to the peptidase T1B family.UniProtP2806521EQUAL219EQUALReactome Database ID Release 71174334Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174334ReactomeR-HSA-1743341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174334.11PSMC426S protease regulatory subunit 6BMIP224MB67 interacting proteinTAT-binding protein-7TBP-7Reactome DB_ID: 174315UniProt:P43686 PSMC4PSMC4MIP224TBP7FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC4 and few additional components (PubMed:27428775,PubMed:27342858). Interacts with NR1I3. Interacts with PAAF1 (PubMed:15831487). Interacts with TRIM5 (PubMed:22078707). Interacts with ZFAND1 (PubMed:29804830).SIMILARITY Belongs to the AAA ATPase family.UniProtP436861EQUAL418EQUALReactome Database ID Release 71174315Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174315ReactomeR-HSA-1743151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174315.11SHFM126S proteasome complex subunit DSS1DSS1_HUMANReactome DB_ID: 8866665UniProt:P60896 SEM1SEM1DSS1SHFDG1SHFM1C7orf76FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:15117943). Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and thus transcription-associated genomic instability. R-loop accumulation increases in SEM1-depleted cells.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including SEM1, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Belongs to the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). Interacts with the C-terminal of BRCA2 (PubMed:10373512, PubMed:21719596).TISSUE SPECIFICITY Expressed in limb bud, craniofacial primordia and skin.SIMILARITY Belongs to the DSS1/SEM1 family.UniProtP608961EQUAL70EQUALReactome Database ID Release 718866665Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8866665ReactomeR-HSA-88666652Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8866665.21PSMB2Proteasome subunit beta type 2 Proteasome component C7-IMacropain subunit C7-IMulticatalytic endopeptidase complex subunit C7-IReactome DB_ID: 174335UniProt:P49721 PSMB2PSMB2FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.SUBUNIT (Microbial infection) Interacts with HIV-1 protein Tat.INDUCTION Up-regulated in ovarian cancer cell lines.SIMILARITY Belongs to the peptidase T1B family.UniProtP497211EQUAL201EQUALReactome Database ID Release 71174335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174335ReactomeR-HSA-1743351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174335.11PSMD726S proteasome non-ATPase regulatory subunit 726S proteasome regulatory subunit S12Proteasome subunit p40Mov34 protein homologReactome DB_ID: 174309UniProt:P51665 PSMD7PSMD7MOV34LFUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD7, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Within the complex, PSMD7 interacts with subunit PSMD4 through their respective MPN domain. Interacts with TRIM5 (PubMed:22078707).MISCELLANEOUS Does not bind a metal ion.SIMILARITY Belongs to the peptidase M67A family.UniProtP516651EQUAL324EQUALReactome Database ID Release 71174309Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174309ReactomeR-HSA-1743091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174309.11PSMC226S protease regulatory subunit 7MSS1 proteinReactome DB_ID: 174332UniProt:P35998 PSMC2PSMC2MSS1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC2 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC2 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with NDC80/HEC; this interaction is detected only during M phase. Interacts and SQSTM1 (PubMed:15340068). Interacts with PAAF1 (PubMed:15831487). Directly interacts with TRIM5 (PubMed:22078707).INDUCTION Expression is not cell cycle-dependent and occurs throughout the cell cycle.SIMILARITY Belongs to the AAA ATPase family.UniProtP359982EQUAL433EQUALReactome Database ID Release 71174332Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174332ReactomeR-HSA-1743321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174332.11PSMD126S proteasome non-ATPase regulatory subunit 126S proteasome regulatory subunit S126S proteasome subunit p112Reactome DB_ID: 174348UniProt:Q99460 PSMD1PSMD1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD1 (PubMed:27428775, PubMed:27342858). Interacts with ADRM1 (PubMed:16990800, PubMed:16906146). Interacts with ZFAND1 (PubMed:29804830).SIMILARITY Belongs to the proteasome subunit S1 family.UniProtQ994601EQUAL953EQUALReactome Database ID Release 71174348Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174348ReactomeR-HSA-1743481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174348.11PSMA3Proteasome subunit alpha type 3 Proteasome component C8Macropain subunit C8Multicatalytic endopeptidase complex subunit C8Reactome DB_ID: 174323UniProt:P25788 PSMA3PSMA3HC8PSC8FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Interacts with AURKB. Interacts with CDKN1A (PubMed:11350925). Interacts with MDM2 and RB1 (PubMed:16337594). Interacts with the C-terminus of TBXA2R isoform 2 (PubMed:17499743). Interacts with DNAJB2 (PubMed:15936278).SUBUNIT (Microbial infection) Interacts with HIV-1 Tat protein.SUBUNIT (Microbial infection) Interacts with hepatitis C virus (HCV) F protein.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA3 proteins.INDUCTION Down-regulated by antioxidants BO-653 and probucol. Up-regulated by bacterial lipopolysaccharides (LPS) and TNF.SIMILARITY Belongs to the peptidase T1A family.UniProtP257882EQUAL255EQUALReactome Database ID Release 71174323Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174323ReactomeR-HSA-1743231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174323.11PSMD1426S proteasome-associated pad1 homologReactome DB_ID: 174329UniProt:O00487 PSMD14PSMD14POH1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD4, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Within the complex, PSMD4 interacts with subunit PSMD7 through their respective MPN domain. Interacts with TXNL1 (PubMed:19349277).TISSUE SPECIFICITY Widely expressed. Highest levels in heart and skeletal muscle.SIMILARITY Belongs to the peptidase M67A family. PSMD14 subfamily.UniProtO004871EQUAL310EQUALReactome Database ID Release 71174329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174329ReactomeR-HSA-1743291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174329.11p44PSMC626S protease regulatory subunit S10BProteasome subunit p42Conserved ATPase domain protein 44CADp44Reactome DB_ID: 174319UniProt:P62333 PSMC6PSMC6SUG2FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC6 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC6 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with PAAF1 (PubMed:15831487).SIMILARITY Belongs to the AAA ATPase family.CAUTION Alternative initiation from an upstream conserved methionine cannot be fully excluded but is not experimentally supported while initiation from the displayed methionine is supported by PubMed:17323924.UniProtP623331EQUAL389EQUALReactome Database ID Release 71174319Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174319ReactomeR-HSA-1743191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174319.11PSME2Proteasome activator complex subunit 2Proteasome activator 28-beta subunitPA28betaPA28bActivator of multicatalytic protease subunit 211S regulator complex beta subunitREG-betaReactome DB_ID: 174350UniProt:Q9UL46 PSME2PSME2FUNCTION Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.SUBUNIT Heterodimer of PSME1 and PSME2, which forms a hexameric ring.INDUCTION By IFNG/IFN-gamma.SIMILARITY Belongs to the PA28 family.UniProtQ9UL462EQUAL239EQUALReactome Database ID Release 71174350Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174350ReactomeR-HSA-1743501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174350.11PSMA7Proteasome subunit alpha type 7 Proteasome subunit RC6-1Proteasome subunit XAPC7Reactome DB_ID: 174351UniProt:O14818 PSMA7PSMA7HSPCFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (PubMed:16251969). Interacts with HIF1A. Interacts with RAB7A (PubMed:14998988). Interacts with PRKN (PubMed:15987638). Interacts with ABL1 and ABL2 (PubMed:16678104). Interacts with EMAP2 (PubMed:19362550). Interacts with MAVS (PubMed:19734229).SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.SUBUNIT (Microbial infection) Interacts with hepatitis B virus X protein (HBX).INDUCTION Down-regulated by the ribozyme Rz3'X. Up-regulated in colorectal cancer tissues.PTM Phosphorylation by ABL1 or ABL2 leads to an inhibition of proteasomal activity and cell cycle transition blocks.SIMILARITY Belongs to the peptidase T1A family.UniProtO148181EQUAL248EQUALReactome Database ID Release 71174351Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174351ReactomeR-HSA-1743511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174351.11PSMB5Proteasome subunit beta type 5Proteasome subunit beta type 5 precursor Proteasome epsilon chainMacropain epsilon chainMulticatalytic endopeptidase complex epsilon chainProteasome subunit XProteasome chain 6Proteasome subunit MB1Reactome DB_ID: 174344UniProt:P28074 PSMB5PSMB5LMPXMB1XFUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. Directly interacts with POMP (PubMed:15944226). Interacts with ABCB1 and TAP1 (PubMed:15488952).SUBUNIT (Microbial infection) Interacts with HIV-1 TAT protein.INDUCTION Down-regulated by IFNG/IFN-gamma (at protein level). Induced in breast cancer tissue. Up-regulated by sulforaphane in breast cancer cells.SIMILARITY Belongs to the peptidase T1B family.UniProtP2807460EQUAL263EQUALReactome Database ID Release 71174344Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174344ReactomeR-HSA-1743441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174344.11PSMD1026S proteasome non-ATPase regulatory subunit 1026S proteasome regulatory subunit p28GankyrinReactome DB_ID: 174322UniProt:O75832 PSMD10PSMD10FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.FUNCTION Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.SUBUNIT Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK.TISSUE SPECIFICITY Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level).CAUTION Was initially identified as a genuine component of the 26S proteasome.UniProtO758321EQUAL226EQUALReactome Database ID Release 71174322Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174322ReactomeR-HSA-1743221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174322.11AFPSMD426S proteasome non-ATPase regulatory subunit 426S proteasome regulatory subunit S5ARpn10Multiubiquitin chain binding proteinAntisecretory factor-1ASFReactome DB_ID: 174330UniProt:P55036 PSMD4PSMD4MCB1FUNCTION Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains.SUBUNIT Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD4 (PubMed:27428775, PubMed:27342858). Interacts with NUB1 (PubMed:11585840). Interacts with SQSTM1 (PubMed:15340068). Interacts with UBQLN4 (PubMed:15280365). Interacts with UBE3A (PubMed:22645313). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878). Interacts with DDI2 (PubMed:29290612).DOMAIN The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way.SIMILARITY Belongs to the proteasome subunit S5A family.UniProtP550361EQUAL377EQUALReactome Database ID Release 71174330Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174330ReactomeR-HSA-1743301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174330.11PSMA5Proteasome subunit alpha type 5 Proteasome zeta chainMacropain zeta chainMulticatalytic endopeptidase complex zeta chainReactome DB_ID: 174340UniProt:P28066 PSMA5PSMA5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. PSMA5 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly.TISSUE SPECIFICITY Expressed in fetal brain (at protein level).INDUCTION Up-regulated in colon cancer cell lines. Up-regulated in fetal Down syndrome (DS) brain (at protein level). May be the target of the transcriptional activator NFE2L2.SIMILARITY Belongs to the peptidase T1A family.UniProtP280661EQUAL241EQUALReactome Database ID Release 71174340Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174340ReactomeR-HSA-1743401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174340.11PSMD526S proteasome non-ATPase regulatory subunit 526S proteasome subunit S5B26S protease subunit S5 basicReactome DB_ID: 174346UniProt:Q16401 PSMD5PSMD5KIAA0072FUNCTION Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5.SUBUNIT Interacts with PSMC1, PSMC2, PSMD1 and PSMD6. Part of transient complex containing PSMD5, PSMC2, PSMC1 and PSMD2 formed during the assembly of the 26S proteasome.DOMAIN Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins.SIMILARITY Belongs to the proteasome subunit S5B/HSM3 family.CAUTION Was initially identified as a genuine component of the 26S proteasome.UniProtQ164012EQUAL504EQUALReactome Database ID Release 71174346Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174346ReactomeR-HSA-1743461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174346.11PSMF1Proteasome inhibitor PI31 subunithPI31Reactome DB_ID: 174308UniProt:Q92530 PSMF1PSMF1FUNCTION Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28.SUBUNIT Monomer and homodimer. Interacts with FBXO7. Interacts with the 20S proteasome.SIMILARITY Belongs to the proteasome inhibitor PI31 family.UniProtQ925301EQUAL271EQUALReactome Database ID Release 71174308Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174308ReactomeR-HSA-1743081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174308.11Reactome Database ID Release 71177750Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177750ReactomeR-HSA-1777502Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177750.2GENE ONTOLOGYGO:0004175Reactome Database ID Release 71174087Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174087Reactome Database ID Release 71174058Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174058ReactomeR-HSA-1740582Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174058.2Reactome Database ID Release 71174084Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174084ReactomeR-HSA-1740843Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174084.3