BioPAX pathway converted from "Signaling by Wnt" in the Reactome database. Signaling by Wnt Signaling by Wnt The beta-catenin destruction complex plays a key role in the canonical Wnt signaling pathway. In the absence of Wnt signaling, this complex controls the levels of cytoplamic beta-catenin. Beta-catenin associates with and is phosphorylated by the destruction complex. Phosphorylated beta-catenin is recognized and ubiquitinated by the SCF-beta TrCP ubiquitin ligase complex and is subsequently degraded by the proteasome (reviewed in Kimelman and Xu, 2006). Authored: Kimelman, D, 2007-04-03 12:34:14 Edited: Matthews, L, 2007-04-03 12:38:03 Degradation of beta-catenin by the destruction complex Degradation of beta-catenin by the destruction complex The beta-catenin destruction complex plays a key role in the canonical Wnt signaling pathway. In the absence of Wnt signaling, this complex controls the levels of cytoplamic beta-catenin. Beta-catenin associates with and is phosphorylated by the destruction complex. Phosphorylated beta-catenin is recognized and ubiquitinated by the SCF-beta TrCP ubiquitin ligase complex and is subsequently degraded by the proteasome (reviewed in Kimelman and Xu, 2006). Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Assembly of the destruction complex Assembly of the destruction complex The exact composition of the destruction complex is not known. A number of components appear to form a core complex, while others may associate with the complex transiently when a Wnt signal is present (reviewed in Kimelman and Xu, 2006). The core components include Axin, glycogen synthase kinase 3 (GSK-3), Casein kinase 1 (CKI) alpha, beta-catenin, Protein phosphatase 2A (PP2A) and Adenomatous Polyposis Coli (APC). CK1 epsilon, Diversin and PP1 may also be components of the complex. Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 196206 1 cytosol GO 0005829 PP2A [cytosol] PP2A Converted from EntitySet in Reactome Reactome DB_ID: 165977 1 PP2A-catalytic subunit C [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome http://www.reactome.org Converted from EntitySet in Reactome Reactome DB_ID: 165990 1 PP2A-subunit A [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Converted from EntitySet in Reactome Reactome DB_ID: 196216 1 PP2A regulatory subunit B [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Homo sapiens NCBI_taxonomy 9606 Reactome 196206 Database 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=196206 Reactome REACT_10628 1 Reactome 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=REACT_10628.1 Reactome DB_ID: 195249 1 UniProt:O15169-1 RecName: Full=Axin-1; AltName: Full=Axis inhibition protein 1; Short=hAxin; GN Name=AXIN1; Synonyms=AXIN; OS Homo sapiens (Human) AXIN AXIN1 FUNCTION: Controls dorsoventral patterning via two opposing effects; down-regulates beta-catenin to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of beta- catenin and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Wild-type axin 1 can induce apoptosis in hepatocellular and colorectal cancer cells. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. SUBUNIT: Homodimer (By similarity). Interacts with TP53 and HIPK2. Probably part of a complex consisting of TP53, HIPK2 and AXIN1. Interacts with glycogen synthase kinase-3 beta (GSK3B) and beta- catenin. The interaction between axin and beta-catenin occurs via the armadillo repeats contained in beta-catenin. Ternary complex. Also binds to plakoglobin (gamma-catenin), APC, DVL and PP2A. Interacts with SMAD6, SMAD7 and RNF111. Interacts with DIXDC1; prevents interaction with MAP3K1. Interacts with MAP3K4, MDFI and MDFIC. Interacts with ANKRD6. Interacts with AIDA. INTERACTION: P39687:ANP32A; NbExp=1; IntAct=EBI-710484, EBI-359234; Q14194:CRMP1; NbExp=1; IntAct=EBI-710484, EBI-473101; Q02248:Ctnnb1 (xeno); NbExp=2; IntAct=EBI-710484, EBI-397872; Q9NRG4:SMYD2; NbExp=1; IntAct=EBI-710484, EBI-1055671; SUBCELLULAR LOCATION: Cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15169-1; Sequence=Displayed; Name=2; IsoId=O15169-2; Sequence=VSP_019398; TISSUE SPECIFICITY: Ubiquitously expressed. PTM: Probably phosphorylated by GSK3B and dephosphorylated by PP2A. DISEASE: Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:114550]. DISEASE: Hypermethylation of the AXIN1 promoter may be associated with caudal duplication anomaly [MIM:607864]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. SIMILARITY: Contains 1 DIX domain. SIMILARITY: Contains 1 RGS domain. UniProt O15169 Reactome DB_ID: 195263 1 UniProt:P48729-1 RecName: Full=Casein kinase I isoform alpha; Short=CKI-alpha; EC=2.7.11.1; AltName: Full=CK1; GN Name=CSNK1A1; OS Homo sapiens (Human) CSNK1A1 FUNCTION: Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 on 'Ser-45'. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. SUBUNIT: Monomer. Interacts with the Axin complex. SUBCELLULAR LOCATION: Cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P48729-1; Sequence=Displayed; Name=2; IsoId=P48729-2; Sequence=VSP_035455; SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. SIMILARITY: Contains 1 protein kinase domain. UniProt P48729 Converted from EntitySet in Reactome Reactome DB_ID: 195269 1 GSK3B [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GSK3B_2 [cytosol] GSK3B_1 [cytosol] UniProt P49841 UniProt P49841 Converted from EntitySet in Reactome Reactome DB_ID: 195265 1 APC [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity APC_2 [cytosol] APC_1 [cytosol] UniProt P25054 UniProt P25054 Reactome DB_ID: 195250 1 Axin:GSK3:CK1alpha:APC:PP2A complex [cytosol] Axin:GSK3:CK1alpha:APC:PP2A complex Reactome DB_ID: 196206 1 Reactome DB_ID: 195249 1 Reactome DB_ID: 195263 1 Converted from EntitySet in Reactome Reactome DB_ID: 195269 1 Converted from EntitySet in Reactome Reactome DB_ID: 195265 1 Reactome 195250 Database 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=195250 Reactome REACT_10218 1 Reactome 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=REACT_10218.1 Reactome 195251 Database 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=195251 Reactome REACT_10134 1 Reactome 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=REACT_10134.1 12554650 Pubmed 2003 Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex Dajani, R Fraser, E Roe, SM Yeo, M Good, VM Thompson, V Dale, TC Pearl, LH EMBO J 22:494-501 17143292 Pubmed 2006 beta-catenin destruction complex: insights and questions from a structural perspective Kimelman, D Xu, W Oncogene 25:7482-91 10092233 Pubmed 1999 Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A Seeling, JM Miller, JR Gil, R Moon, RT White, R Virshup, DM Science 283:2089-91 Association of beta-catenin with the destruction complex Association of beta-catenin with the destruction complex Beta-catenin associates with the destruction complex through an interaction with Axin and or APC. This association may also involve interactions with the 15 aa repeats in APC (Spink et al., 2001) or the third APC 20aa repeat and its N-terminal flanking residues (Ha et al., 2004, Xing et al., 2004; Liu et al., 2006). Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 195250 1 Converted from EntitySet in Reactome Reactome DB_ID: 191727 1 beta-catenin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 195301 1 beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex [cytosol] beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex Reactome DB_ID: 195250 1 Converted from EntitySet in Reactome Reactome DB_ID: 191727 1 Reactome 195301 Database 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=195301 Reactome REACT_10837 1 Reactome 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=REACT_10837.1 Reactome 195304 Database 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=195304 Reactome REACT_10111 1 Reactome 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=REACT_10111.1 11707392 Pubmed 2001 Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex Eklof Spink, K Fridman, SG Weis, WI EMBO J 20:6203-12 15327769 Pubmed 2004 Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function Xing, Y Clements, WK Le Trong, I Hinds, TR Stenkamp, R Kimelman, D Xu, W Mol Cell 15:523-33 16753179 Pubmed 2006 The third 20 amino acid repeat is the tightest binding site of APC for beta-catenin Liu, J Xing, Y Hinds, TR Zheng, J Xu, W J Mol Biol 360:133-44 15327768 Pubmed 2004 Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation Ha, NC Tonozuka, T Stamos, JL Choi, HJ Weis, WI Mol Cell 15:511-21 Beta-catenin phosphorylation cascade Beta-catenin phosphorylation cascade Degradation of beta-catenin is initiated following amino-terminal serine/threonine phosphorylation. Phosphorylation of B-catenin at S45 by CK1 alpha primes the subsequent sequential GSK-3-mediated phosphorylation at Thr41, Ser37 and Ser33 (Amit et al., 2002 ; Lui et al., 2002). Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-19 08:07:52 Phosphorylation of beta-catenin at Ser45 by CK1 alpha Phosphorylation of beta-catenin at Ser45 by CK1 alpha CK1a binds to Axin and phosphorylates beta-catenin at Ser45 priming GSK3 mediated phosphorylation at the more N-terminal residues (Amit et al., 2002; Liu et al., 2002; Yanagawa et al., 2002). Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 113592 1 ATP [ChEBI:15422] ATP Adenosine 5'-triphosphate ChEBI 15422 Reactome DB_ID: 195301 1 Reactome DB_ID: 29370 1 ADP [ChEBI:16761] ADP Adenosine 5'-diphosphate ChEBI 16761 Reactome DB_ID: 195277 1 phospho-(Ser45) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex [cytosol] phospho-(Ser45) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex Converted from EntitySet in Reactome Reactome DB_ID: 195309 1 phospho-(Ser45) beta-catenin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-(Ser45) beta-catenin_1 [cytosol] phospho-(Ser45) beta-catenin_2 [cytosol] UniProt P35222 UniProt P35222 Reactome DB_ID: 195250 1 Reactome 195277 Database 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=195277 Reactome REACT_10809 1 Reactome 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=REACT_10809.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 195282 Phospho-(Ser45, Thr41, Ser37, Ser33) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex [cytosol] Phospho-(Ser45, Thr41, Ser37, Ser33) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex Reactome DB_ID: 195250 1 Converted from EntitySet in Reactome Reactome DB_ID: 195274 1 phosph-(Ser45, Thr41, Ser37, Ser33) beta-catenin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-(Ser45, Thr41, Ser37, Ser33)beta-catenin_2 [cytosol] Phospho (4 sites) beta-catenin [cytosol] Reactome 195282 Database 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=195282 Reactome REACT_10610 1 Reactome 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=REACT_10610.1 GO 0016301 GO molecular function Reactome 195306 Database 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=195306 Reactome 195318 Database 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=195318 Reactome REACT_9978 1 Reactome 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=REACT_9978.1 12000790 Pubmed 2002 Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway Amit, S Hatzubai, A Birman, Y Andersen, JS Ben-Shushan, E Mann, M Ben-Neriah, Y Alkalay, I Genes Dev 16:1066-76 Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3 Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3 Following CKI-mediated phosphorylation at Ser45, beta-catenin is phosphorylated by GSK3 at Thr41. Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 113592 1 Reactome DB_ID: 195277 1 Reactome DB_ID: 195313 1 phospho-(Ser45, Thr41) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex [cytosol] phospho-(Ser45, Thr41) beta-catenin:Axin:GSK3:CK1alpha:APC:PP2A complex Reactome DB_ID: 195250 1 Converted from EntitySet in Reactome Reactome DB_ID: 195290 1 phospho-(Ser45,Thr41) beta catenin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-(Ser45, Thr41) beta catenin_1 [cytosol] phospho-(Ser45, Thr41) beta catenin_2 [cytosol] Reactome 195313 Database 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=195313 Reactome REACT_10844 1 Reactome 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=REACT_10844.1 Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 195277 Reactome 196226 Database 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=196226 Reactome 195287 Database 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=195287 Reactome REACT_9955 1 Reactome 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=REACT_9955.1 11955436 Pubmed 2002 Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism Liu, C Li, Y Semenov, M Han, C Baeg, GH Tan, Y Zhang, Z Lin, X He, X Cell 108:837-47 Phosphoryation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3 Phosphoryation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3 Phospho-(Ser45, Thr41) beta-catenin is phosphorylated by GSK3 at Ser37. Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 195313 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 195305 1 phospho-(Ser45, Thr41, Ser37) beta-catenin:Axin,GSK3:CK1alpha:APC:PP2A complex [cytosol] phospho-(Ser45, Thr41, Ser37) beta-catenin:Axin,GSK3:CK1alpha:APC:PP2A complex Converted from EntitySet in Reactome Reactome DB_ID: 195316 1 phospho-(Ser45,Thr41,Ser37) beta-catenin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-(Ser45, Thr41, Ser37) beta-catenin_2 [cytosol] phospho-(Ser45, Thr41, Ser37) beta-catenin_1 [cytosol] Reactome DB_ID: 195250 1 Reactome 195305 Database 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=195305 Reactome REACT_10861 1 Reactome 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=REACT_10861.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 195313 Reactome 196225 Database 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=196225 Reactome 195283 Database 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=195283 Reactome REACT_9959 1 Reactome 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=REACT_9959.1 Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3 Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3 Beta-catenin is then phosphorylated at Ser33. Phosphorylated S37 and S33 together with neighboring residues constitute the recognition motif for beta-TrCP. Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 113592 1 Reactome DB_ID: 195305 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 195282 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 195282 Reactome 196224 Database 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=196224 Reactome 195300 Database 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=195300 Reactome REACT_9987 1 Reactome 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=REACT_9987.1 Reactome 196299 Database 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=196299 Reactome REACT_11065 1 Reactome 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=REACT_11065.1 Phosphorylation of APC component of the destruction complex Phosphorylation of APC component of the destruction complex APC is phosphorylated on the 20 aa repeats by CK1 and potentially GSK-3. This significantly increases the binding affinity of the GSK-3 20 aa repeats for beta-catenin, causing one of them to bind b-catenin in the same region as beta-catenin binds Axin, thus displacing beta-catenin from Axin ( Step 5 above) (Reviewed in Kimelman, 2006). Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 113592 1 Reactome DB_ID: 195282 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 195297 1 phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex [cytosol] phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex Converted from EntitySet in Reactome Reactome DB_ID: 195293 1 phospho-APC [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-APC_1 [cytosol] phospho-APC_2 [cytosol] Reactome DB_ID: 196206 1 Reactome DB_ID: 195249 1 Reactome DB_ID: 195263 1 Converted from EntitySet in Reactome Reactome DB_ID: 195269 1 Converted from EntitySet in Reactome Reactome DB_ID: 195274 1 Reactome 195297 Database 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=195297 Reactome REACT_10660 1 Reactome 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=REACT_10660.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 195282 Reactome 195275 Database 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=195275 Reactome REACT_9983 2 Reactome 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=REACT_9983.2 12628243 Pubmed 2003 Differences between the interaction of beta-catenin with non-phosphorylated and single-mimicked phosphorylated 20-amino acid residue repeats of the APC protein Tickenbrock, L Kossmeier, K Rehmann, H Herrmann, C Muller, O J Mol Biol 327:359-67 Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex The phosphorylation of the 20 aa repeats in APC results in an increase in affinity for beta-catenin (Ha et al., 2004, Xing et al., 2004; Liu et al., 2006). The binding site of phospho -(20 aa) APC on beta-catenin, overlaps the binding site of Axin on beta catenin. In addition, phosphorylated APC prevents the association of Axin with beta-catenin (Ha et al., 2004, Xing et al., 2004). In this model, phosphorylated APC may compete with Axin for beta-catenin binding, resulting in dissociation of the Axin:beta-catenin interaction in the destruction complex (see Kimelman and Xu 2006). Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 195297 1 Reactome DB_ID: 195322 1 phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex [cytosol] phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex Converted from EntitySet in Reactome Reactome DB_ID: 195293 1 Reactome DB_ID: 196206 1 Reactome DB_ID: 195249 1 Reactome DB_ID: 195263 1 Converted from EntitySet in Reactome Reactome DB_ID: 195269 1 Converted from EntitySet in Reactome Reactome DB_ID: 195274 1 Reactome 195322 Database 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=195322 Reactome REACT_10886 1 Reactome 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=REACT_10886.1 Reactome 195280 Database 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=195280 Reactome REACT_10127 1 Reactome 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=REACT_10127.1 Association of beta-catenin with the SCF-beta-TrCP1 ubiquitin ligase complex Association of beta-catenin with the SCF-beta-TrCP1 ubiquitin ligase complex B-TrCP associates with phosphorylated beta-catenin through the B-TrCP WD40 repeat region. Currently, it is unclear whether the ubiquitin ligase binds beta-catenin after it leaves the complex. It is equally possible that it binds beta-catenin while beta-catenin is still bound to Axin. Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 174155 1 SCF-beta-TrCP1 complex [cytosol] SCF-beta-TrCP1 complex Reactome DB_ID: 174230 1 UniProt:Q13616 RecName: Full=Cullin-1; Short=CUL-1; GN Name=CUL1; OS Homo sapiens (Human) CUL1 FUNCTION: Core component of multiple cullin-RING-based SCF (SKP1- CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participates in Wnt signaling. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(SKP2) directs ubiquination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquination of ORC1L, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1 (By similarity). SCF(FBXO11) does not seem to direct ubiquitination of TP53. Interacts with FBXW8. Interacts with CUL7; the interaction seems to be mediated by FBXW8 (By similarity). PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin- protein ligase complexes formed of CUL1, SKP1A, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(BTRC) complex containing BTRC. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXw2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Interacts with RNF7. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction negatively regulates the association with SKP1 in the SCF complex. Interacts with COPS2. Can self-associate. INTERACTION: Q86VP6:CAND1; NbExp=6; IntAct=EBI-359390, EBI-456077; Q8N668:COMMD1; NbExp=1; IntAct=EBI-359390, EBI-1550112; Q9UKT5:FBXO4; NbExp=1; IntAct=EBI-359390, EBI-960409; P62136:PPP1CA; NbExp=1; IntAct=EBI-359390, EBI-357253; P62877:RBX1; NbExp=4; IntAct=EBI-359390, EBI-398523; Q9NS64:RPRM; NbExp=1; IntAct=EBI-359390, EBI-1052363; P63208:SKP1; NbExp=2; IntAct=EBI-359390, EBI-307486; Q13309:SKP2; NbExp=2; IntAct=EBI-359390, EBI-456291; TISSUE SPECIFICITY: Expressed in lung fibroblasts. PTM: Neddylated; which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. SIMILARITY: Belongs to the cullin family. UniProt Q13616 Reactome DB_ID: 174237 1 UniProt:Q9Y297-1 RecName: Full=F-box/WD repeat-containing protein 1A; AltName: Full=F-box and WD repeats protein beta-TrCP; AltName: Full=E3RSIkappaB; AltName: Full=pIkappaBalpha-E3 receptor subunit; GN Name=BTRC; Synonyms=BTRCP, FBW1A, FBXW1A; OS Homo sapiens (Human) BTRC FBW1A BTRCP FBXW1A FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling. SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, SMAD3, SMAD4, CDC25A, DLG1, FBXO5 and probably NFKB2. May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Self-associates. Component of the SCF(BTRC) complex formed of CUL1, SKP1A, RBX1 and a BTRC dimer, in which it interacts directly with SKP1A. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, SMAD3, SMAD4, CDC25A, DLG1 and FBXO5; the interaction requires the phosphorylation of the two serine residues in the destruction motif D-S-G-X(2,3)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with HIV-1 Vpu. Interacts with FBXW11. Interacts with CUL4A and DDB1. INTERACTION: P30291:WEE1; NbExp=1; IntAct=EBI-307461, EBI-914695; SUBCELLULAR LOCATION: Cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9Y297-1; Sequence=Displayed; Name=2; IsoId=Q9Y297-2; Sequence=VSP_006764; SIMILARITY: Contains 1 F-box domain. SIMILARITY: Contains 7 WD repeats. UniProt Q9Y297 Reactome DB_ID: 174150 1 UniProt:P63208-1 RecName: Full=S-phase kinase-associated protein 1; AltName: Full=Cyclin A/CDK2-associated protein p19; AltName: Full=p19skp1; AltName: Full=p19A; AltName: Full=RNA polymerase II elongation factor-like protein; AltName: Full=Organ of Corti protein 2; Short=OCP-2; AltName: Full=OCP-II; AltName: Full=Transcription elongation factor B; Short=SIII; GN Name=SKP1; Synonyms=EMC19, OCP2, SKP1A, TCEB1L; OS Homo sapiens (Human) EMC19 TCEB1L SKP1A SKP1 OCP2 FUNCTION: Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts directly with CUL1 and F-box proteins, such as BTRC and SKP2, in the SCF complex. Interacts with the cyclin A/CDK2 complex. Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. INTERACTION: Q13616:CUL1; NbExp=2; IntAct=EBI-307486, EBI-359390; Q9Y2K7:FBXL11; NbExp=1; IntAct=EBI-307486, EBI-765758; Q9UJT9:FBXL7; NbExp=1; IntAct=EBI-307486, EBI-914660; Q8TF61:FBXO41; NbExp=1; IntAct=EBI-307486, EBI-914807; Q9UKT8:FBXW2; NbExp=1; IntAct=EBI-307486, EBI-914727; Q969U6:FBXW5; NbExp=1; IntAct=EBI-307486, EBI-741068; Q969H0:FBXW7; NbExp=1; IntAct=EBI-307486, EBI-359574; Q8N3Y1:FBXW8; NbExp=1; IntAct=EBI-307486, EBI-914770; P62136:PPP1CA; NbExp=2; IntAct=EBI-307486, EBI-357253; P36873-1:PPP1CC; NbExp=1; IntAct=EBI-307486, EBI-356289; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P63208-1, P34991-1; Sequence=Displayed; Name=2; IsoId=P63208-2, P34991-2; Sequence=VSP_007555; Note=No experimental confirmation available; SIMILARITY: Belongs to the SKP1 family. UniProt P63208 Reactome 174155 Database 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=174155 Reactome REACT_6992 2 Reactome 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=REACT_6992.2 Reactome DB_ID: 195297 1 Reactome DB_ID: 195311 1 SCF-beta-TrCP1 complex associated with phosphorylated beta-catenin [cytosol] SCF-beta-TrCP1 complex associated with phosphorylated beta-catenin Reactome DB_ID: 174155 1 Reactome DB_ID: 195297 1 Reactome 195311 Database 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=195311 Reactome REACT_10593 1 Reactome 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=REACT_10593.1 Reactome 195285 Database 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=195285 Reactome REACT_9977 1 Reactome 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=REACT_9977.1 10023660 Pubmed 1999 The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin Latres, E Chiaur, DS Pagano, M Oncogene 18:849-54 9990852 Pubmed 1999 The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro Winston, JT Strack, P Beer-Romero, P Chu, CY Elledge, SJ Harper, JW Genes Dev 13:270-83 Multi-ubiquitination of phospho-beta-catenin by SCF-beta-TrCP1 Multi-ubiquitination of phospho-beta-catenin by SCF-beta-TrCP1 Beta-catenin is ubiquitinated by the SCF-B-TrCP1 complex. Authored: Kimelman, D, 2007-04-03 12:34:14 Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-03 12:38:03 Reactome DB_ID: 113595 4 UniProt:P62988 RecName: Full=Ubiquitin; GN Name=RPS27A; Synonyms=UBA80, UBCEP1; GN and GN Name=UBA52; Synonyms=UBCEP2; GN and GN Name=UBB; GN and GN Name=UBC; OS Homo sapiens (Human) UBC UBB UBA80 UBCEP2 UBA52 RPS27A UBCEP1 FUNCTION: Protein modifier which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Attachment to proteins as a Lys-48-linked polymer usually leads to their degradation by proteasome. Attachment to proteins as a monomer or as an alternatively linked polymer does not lead to proteasomal degradation and may be required for numerous functions, including maintenance of chromatin structure, regulation of gene expression, stress response, ribosome biogenesis and DNA repair. INTERACTION: P48524:BUL1 (xeno); NbExp=1; IntAct=EBI-413034, EBI-3881; Q8IVM0:CCDC50; NbExp=1; IntAct=EBI-413034, EBI-723996; Q99741:CDC6; NbExp=1; IntAct=EBI-413034, EBI-374862; P28562:DUSP1; NbExp=1; IntAct=EBI-413034, EBI-975493; Q9CZV8:Fbxl20 (xeno); NbExp=1; IntAct=EBI-413034, EBI-1551033; Q9UJY5:GGA1; NbExp=1; IntAct=EBI-413034, EBI-447141; Q96J02:ITCH; NbExp=1; IntAct=EBI-413034, EBI-1564678; Q60592:Mast2 (xeno); NbExp=2; IntAct=EBI-413034, EBI-493888; P33993:MCM7; NbExp=1; IntAct=EBI-413034, EBI-355924; Q00987:MDM2; NbExp=1; IntAct=EBI-413034, EBI-389668; Q9UM54:MYO6; NbExp=1; IntAct=EBI-413034, EBI-350606; P46934:NEDD4; NbExp=1; IntAct=EBI-413034, EBI-726944; Q13415:ORC1L; NbExp=1; IntAct=EBI-413034, EBI-374847; Q9UJ41:RABGEF1; NbExp=2; IntAct=EBI-413034, EBI-913954; Q8IYW5:RNF168; NbExp=1; IntAct=EBI-413034, EBI-914207; Q68DV7:RNF43; NbExp=1; IntAct=EBI-413034, EBI-1647060; Q9HAU4:SMURF2; NbExp=1; IntAct=EBI-413034, EBI-396727; P04637:TP53; NbExp=1; IntAct=EBI-413034, EBI-366083; O14048:ubx2 (xeno); NbExp=1; IntAct=EBI-413034, EBI-1005194; Q9UT81:ubx3 (xeno); NbExp=1; IntAct=EBI-413034, EBI-1005297; O00308:WWP2; NbExp=1; IntAct=EBI-413034, EBI-743923; Q96PM9:ZNF385A; NbExp=1; IntAct=EBI-413034, EBI-1539778; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. PTM: Several types of polymeric chains can be formed, depending on the lysine used for the assembly. MISCELLANEOUS: Ubiquitin is synthesized as a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. In some species there is a final amino-acid after the last repeat, here in human a Val. Some ubiquitin genes contain a single copy of ubiquitin fused to a ribosomal protein (either L40 or S27a). SIMILARITY: Belongs to the ubiquitin family. UniProt P62988 Chain Coordinates 1 EQUAL 76 EQUAL Reactome DB_ID: 195311 1 Reactome DB_ID: 195303 1 ubiquitinated phospho-beta-catenin:SCF:beta-TrCP1 complex [cytosol] ubiquitinated phospho-beta-catenin:SCF:beta-TrCP1 complex Reactome DB_ID: 113595 4 1 EQUAL 76 EQUAL Reactome DB_ID: 195311 1 Reactome 195303 Database 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=195303 Reactome REACT_10202 1 Reactome 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=REACT_10202.1 Reactome 195279 Database 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=195279 Reactome REACT_10082 1 Reactome 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=REACT_10082.1 12820959 Pubmed 2003 Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase Wu, G Xu, G Schulman, BA Jeffrey, PD Harper, JW Pavletich, NP Mol Cell 11:1445-56 Degradation of ubiquitinated -beta catenin by the proteasome Degradation of ubiquitinated -beta catenin by the proteasome Ubiquitinated beta-catenin is degraded by the proteasome. Reviewed: Pagano, M, 2007-04-27 13:02:18 Edited: Matthews, L, 2007-04-19 13:48:27 Reactome DB_ID: 195303 1 Reactome DB_ID: 113595 4 1 EQUAL 76 EQUAL Reactome DB_ID: 174155 1 Reactome DB_ID: 196222 1 phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex [cytosol] phospho-(Ser45,Thr41,Ser37,Ser33):Axin:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A complex Converted from EntitySet in Reactome Reactome DB_ID: 195293 1 Reactome DB_ID: 196206 1 Reactome DB_ID: 195249 1 Reactome DB_ID: 195263 1 Converted from EntitySet in Reactome Reactome DB_ID: 195269 1 Reactome 196222 Database 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=196222 Reactome REACT_10381 1 Reactome 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=REACT_10381.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 68819 26S proteasome [cytosol] 26S proteasome Reactome DB_ID: 68796 1 UniProt:Q13200 RecName: Full=26S proteasome non-ATPase regulatory subunit 2; AltName: Full=26S proteasome regulatory subunit RPN1; AltName: Full=26S proteasome regulatory subunit S2; AltName: Full=26S proteasome subunit p97; AltName: Full=Tumor necrosis factor type 1 receptor-associated protein 2; AltName: Full=55.11 protein; GN Name=PSMD2; Synonyms=TRAP2; OS Homo sapiens (Human) TRAP2 PSMD2 FUNCTION: Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. 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. INTERACTION: P23508:MCC; NbExp=1; IntAct=EBI-357648, EBI-307531; Q92597:NDRG1; NbExp=1; IntAct=EBI-357648, EBI-716486; Q9HC98:NEK6; NbExp=1; IntAct=EBI-357648, EBI-740364; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357648, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357648, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357648, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357648, EBI-359701; Q9P2S5:WDR8; NbExp=1; IntAct=EBI-357648, EBI-1054904; TISSUE SPECIFICITY: Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung and placenta. SIMILARITY: Belongs to the proteasome subunit S2 family. SIMILARITY: Contains 7 PC repeats. UniProt Q13200 Reactome DB_ID: 68744 1 UniProt:P49721 RecName: Full=Proteasome subunit beta type-2; EC=3.4.25.1; AltName: Full=Proteasome component C7-I; AltName: Full=Macropain subunit C7-I; AltName: Full=Multicatalytic endopeptidase complex subunit C7-I; GN Name=PSMB2; OS Homo sapiens (Human) PSMB2 FUNCTION: 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 has a chymotrypsin-like activity. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt P49721 Reactome DB_ID: 68774 1 UniProt:P17980 RecName: Full=26S protease regulatory subunit 6A; AltName: Full=Proteasome 26S subunit ATPase 3; AltName: Full=TAT-binding protein 1; Short=TBP-1; AltName: Full=Proteasome subunit P50; GN Name=PSMC3; Synonyms=TBP1; OS Homo sapiens (Human) TBP1 PSMC3 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex (By similarity). In case of HIV-1 infection, suppresses Tat-mediated transactivation. SUBUNIT: May form a heterodimer with a related family member. Interacts with PAAF1. Interacts with HIV-1 Tat. INTERACTION: P28566:HTR1E; NbExp=1; IntAct=EBI-359720, EBI-1043151; Q92597:NDRG1; NbExp=1; IntAct=EBI-359720, EBI-716486; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-359720, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-359720, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-359720, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-359720, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm (Potential). Nucleus (Potential). SIMILARITY: Belongs to the AAA ATPase family. UniProt P17980 Reactome DB_ID: 68780 1 UniProt:P62195 RecName: Full=26S protease regulatory subunit 8; AltName: Full=Proteasome 26S subunit ATPase 5; AltName: Full=Proteasome subunit p45; AltName: Full=p45/SUG; AltName: Full=Thyroid hormone receptor-interacting protein 1; Short=TRIP1; GN Name=PSMC5; Synonyms=SUG1; OS Homo sapiens (Human) SUG1 PSMC5 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. SUBUNIT: 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 NDC80. Interacts with PAAF1. INTERACTION: P19447:ERCC3; NbExp=1; IntAct=EBI-357745, EBI-1183307; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357745, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357745, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357745, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357745, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm (Potential). Nucleus (Potential). SIMILARITY: Belongs to the AAA ATPase family. UniProt P62195 Reactome DB_ID: 68804 1 UniProt:Q15008 RecName: Full=26S proteasome non-ATPase regulatory subunit 6; AltName: Full=26S proteasome regulatory subunit S10; AltName: Full=p42A; AltName: Full=Proteasome regulatory particle subunit p44S10; AltName: Full=Phosphonoformate immuno-associated protein 4; AltName: Full=Breast cancer-associated protein SGA-113M; GN Name=PSMD6; Synonyms=KIAA0107, PFAAP4; OS Homo sapiens (Human) PFAAP4 PSMD6 KIAA0107 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the PA700 complex. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-359701, EBI-1056358; P25787:PSMA2; NbExp=1; IntAct=EBI-359701, EBI-603262; P28074:PSMB5; NbExp=1; IntAct=EBI-359701, EBI-357828; P62191:PSMC1; NbExp=1; IntAct=EBI-359701, EBI-357598; P35998:PSMC2; NbExp=1; IntAct=EBI-359701, EBI-359710; P17980:PSMC3; NbExp=1; IntAct=EBI-359701, EBI-359720; P43686:PSMC4; NbExp=1; IntAct=EBI-359701, EBI-743997; P62195:PSMC5; NbExp=1; IntAct=EBI-359701, EBI-357745; P62333:PSMC6; NbExp=1; IntAct=EBI-359701, EBI-357669; Q99460:PSMD1; NbExp=1; IntAct=EBI-359701, EBI-357874; O75832:PSMD10; NbExp=1; IntAct=EBI-359701, EBI-752185; O00231:PSMD11; NbExp=1; IntAct=EBI-359701, EBI-357816; O00232:PSMD12; NbExp=1; IntAct=EBI-359701, EBI-359733; Q9UNM6:PSMD13; NbExp=1; IntAct=EBI-359701, EBI-356070; O00487:PSMD14; NbExp=1; IntAct=EBI-359701, EBI-722193; Q13200:PSMD2; NbExp=1; IntAct=EBI-359701, EBI-357648; O43242:PSMD3; NbExp=1; IntAct=EBI-359701, EBI-357622; P55036:PSMD4; NbExp=1; IntAct=EBI-359701, EBI-359318; P51665:PSMD7; NbExp=1; IntAct=EBI-359701, EBI-357659; P48556:PSMD8; NbExp=1; IntAct=EBI-359701, EBI-359304; Q9Y4R8:TELO2; NbExp=1; IntAct=EBI-359701, EBI-1043674; SIMILARITY: Belongs to the proteasome subunit S10 family. SIMILARITY: Contains 1 PCI domain. UniProt Q15008 Reactome DB_ID: 68771 1 UniProt:P35998 RecName: Full=26S protease regulatory subunit 7; AltName: Full=Proteasome 26S subunit ATPase 2; AltName: Full=Protein MSS1; GN Name=PSMC2; Synonyms=MSS1; OS Homo sapiens (Human) MSS1 PSMC2 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. In case of HIV-1 infection, positive modulator of Tat-mediated transactivation. SUBUNIT: Interacts with NDC80 and SQSTM1. Interacts with PAAF1. Interacts with HIV-1 Tat. INTERACTION: Q92597:NDRG1; NbExp=1; IntAct=EBI-359710, EBI-716486; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-359710, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-359710, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-359710, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-359710, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the AAA ATPase family. UniProt P35998 Reactome DB_ID: 68818 1 UniProt:Q92530 RecName: Full=Proteasome inhibitor PI31 subunit; Short=hPI31; GN Name=PSMF1; OS Homo sapiens (Human) PSMF1 FUNCTION: 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 (Probable). INTERACTION: Q9NWB1:FOX1; NbExp=1; IntAct=EBI-945916, EBI-945906; SIMILARITY: Belongs to the proteasome inhibitor PI31 family. UniProt Q92530 Reactome DB_ID: 68736 1 UniProt:O14818-1 RecName: Full=Proteasome subunit alpha type-7; EC=3.4.25.1; AltName: Full=Proteasome subunit RC6-1; AltName: Full=Proteasome subunit XAPC7; GN Name=PSMA7; OS Homo sapiens (Human) PSMA7 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly. INTERACTION: Self; NbExp=1; IntAct=EBI-603272, EBI-603272; Q14164:IKBKE; NbExp=1; IntAct=EBI-603272, EBI-307369; P22392:NME2; NbExp=1; IntAct=EBI-603272, EBI-713693; P25786:PSMA1; NbExp=3; IntAct=EBI-603272, EBI-359352; P25787:PSMA2; NbExp=1; IntAct=EBI-603272, EBI-603262; P25788:PSMA3; NbExp=1; IntAct=EBI-603272, EBI-348380; P25789:PSMA4; NbExp=4; IntAct=EBI-603272, EBI-359310; P28066:PSMA5; NbExp=1; IntAct=EBI-603272, EBI-355475; P60900:PSMA6; NbExp=3; IntAct=EBI-603272, EBI-357793; P16035:TIMP2; NbExp=1; IntAct=EBI-603272, EBI-1033507; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Comment=Experimental confirmation may be lacking for some isoforms; Name=1; IsoId=O14818-1; Sequence=Displayed; Name=2; IsoId=O14818-2; Sequence=VSP_005281; Name=3; IsoId=O14818-4; Sequence=Not described; SIMILARITY: Belongs to the peptidase T1A family. UniProt O14818 Reactome DB_ID: 68730 1 UniProt:P25789 RecName: Full=Proteasome subunit alpha type-4; EC=3.4.25.1; AltName: Full=Proteasome component C9; AltName: Full=Macropain subunit C9; AltName: Full=Multicatalytic endopeptidase complex subunit C9; AltName: Full=Proteasome subunit L; GN Name=PSMA4; Synonyms=PSC9; OS Homo sapiens (Human) PSC9 PSMA4 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: Self; NbExp=1; IntAct=EBI-359310, EBI-359310; P25786:PSMA1; NbExp=1; IntAct=EBI-359310, EBI-359352; P25787:PSMA2; NbExp=3; IntAct=EBI-359310, EBI-603262; P25788:PSMA3; NbExp=1; IntAct=EBI-359310, EBI-348380; P28066:PSMA5; NbExp=1; IntAct=EBI-359310, EBI-355475; P60900:PSMA6; NbExp=1; IntAct=EBI-359310, EBI-357793; O14818:PSMA7; NbExp=4; IntAct=EBI-359310, EBI-603272; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1A family. UniProt P25789 Reactome DB_ID: 68765 1 UniProt:P28065-1 RecName: Full=Proteasome subunit beta type-9; EC=3.4.25.1; AltName: Full=Proteasome subunit beta-1i; AltName: Full=Proteasome chain 7; AltName: Full=Macropain chain 7; AltName: Full=Multicatalytic endopeptidase complex chain 7; AltName: Full=RING12 protein; AltName: Full=Low molecular mass protein 2; Flags: Precursor; GN Name=PSMB9; Synonyms=LMP2, RING12; OS Homo sapiens (Human) LMP2 RING12 PSMB9 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit is part of the immunoproteasome where it displaces the equivalent houskeeping subunit PSMB6. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=LMP2.L; IsoId=P28065-1; Sequence=Displayed; Name=LMP2.S; IsoId=P28065-2; Sequence=VSP_005288; INDUCTION: By interferon gamma. 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. UniProt P28065 Reactome DB_ID: 68753 1 UniProt:P28074 RecName: Full=Proteasome subunit beta type-5; EC=3.4.25.1; AltName: Full=Proteasome epsilon chain; AltName: Full=Macropain epsilon chain; AltName: Full=Multicatalytic endopeptidase complex epsilon chain; AltName: Full=Proteasome subunit X; AltName: Full=Proteasome chain 6; AltName: Full=Proteasome subunit MB1; Flags: Precursor; GN Name=PSMB5; Synonyms=LMPX; OS Homo sapiens (Human) PSMB5 LMPX FUNCTION: 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. May catalyze basal processing of intracellular antigens. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit can be displaced by the equivalent immune-specific subunit PSMB8. Directly interacts with POMP. INTERACTION: O15116:LSM1; NbExp=1; IntAct=EBI-357828, EBI-347619; Q15008:PSMD6; NbExp=1; IntAct=EBI-357828, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt P28074 Reactome DB_ID: 68783 1 UniProt:P62333 RecName: Full=26S protease regulatory subunit S10B; AltName: Full=Proteasome 26S subunit ATPase 6; AltName: Full=Proteasome subunit p42; GN Name=PSMC6; Synonyms=SUG2; OS Homo sapiens (Human) PSMC6 SUG2 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. SUBUNIT: Found in the multi-protein complexes: the 26S proteasome (formed from the 20S proteasome and PA700), and the modulator. PA700 consists of 28 subunits arranged to form a cylinder-shaped complex by four stacked rings, each containing seven subunits. Interacts with PAAF1. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357669, EBI-1056358; O75832:PSMD10; NbExp=1; IntAct=EBI-357669, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357669, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). SIMILARITY: Belongs to the AAA ATPase family. UniProt P62333 Reactome DB_ID: 68816 1 UniProt:P61289-1 RecName: Full=Proteasome activator complex subunit 3; AltName: Full=Proteasome activator 28 subunit gamma; Short=PA28gamma; Short=PA28g; AltName: Full=Activator of multicatalytic protease subunit 3; AltName: Full=11S regulator complex subunit gamma; Short=REG-gamma; AltName: Full=Ki nuclear autoantigen; GN Name=PSME3; OS Homo sapiens (Human) PSME3 FUNCTION: 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: Homohexamer. INTERACTION: Self; NbExp=2; IntAct=EBI-355546, EBI-355546; P23508:MCC; NbExp=1; IntAct=EBI-355546, EBI-307531; Q9Y6Q9:NCOA3; NbExp=4; IntAct=EBI-355546, EBI-81196; Q15287:RNPS1; NbExp=1; IntAct=EBI-355546, EBI-395959; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P61289-1, Q12920-1; Sequence=Displayed; Name=2; IsoId=P61289-2, Q12920-2; Sequence=VSP_004516; DISEASE: Sera from patients with systemic lupus erythematosus often contain antibodies that react with the Ki antigen. SIMILARITY: Belongs to the PA28 family. UniProt P61289 Reactome DB_ID: 68722 1 UniProt:O00487 RecName: Full=26S proteasome non-ATPase regulatory subunit 14; AltName: Full=26S proteasome regulatory subunit rpn11; AltName: Full=26S proteasome-associated PAD1 homolog 1; GN Name=PSMD14; Synonyms=POH1; OS Homo sapiens (Human) PSMD14 POH1 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the 19S regulatory cap of the 26S proteasome. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-722193, EBI-1056358; Q15008:PSMD6; NbExp=1; IntAct=EBI-722193, EBI-359701; TISSUE SPECIFICITY: Widely expressed. Highest levels in heart and skeletal muscle. SIMILARITY: Belongs to the peptidase M67A family. SIMILARITY: Contains 1 MPN (JAB/Mov34) domain. UniProt O00487 Reactome DB_ID: 68792 1 UniProt:O00232 RecName: Full=26S proteasome non-ATPase regulatory subunit 12; AltName: Full=26S proteasome regulatory subunit p55; GN Name=PSMD12; OS Homo sapiens (Human) PSMD12 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the PA700 complex. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-359733, EBI-1056358; O75832:PSMD10; NbExp=1; IntAct=EBI-359733, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-359733, EBI-359701; SIMILARITY: Belongs to the proteasome subunit p55 family. SIMILARITY: Contains 1 PCI domain. UniProt O00232 Reactome DB_ID: 68741 1 UniProt:P40306 RecName: Full=Proteasome subunit beta type-10; EC=3.4.25.1; AltName: Full=Proteasome subunit beta-2i; AltName: Full=Proteasome MECl-1; AltName: Full=Macropain subunit MECl-1; AltName: Full=Multicatalytic endopeptidase complex subunit MECl-1; Flags: Precursor; GN Name=PSMB10; Synonyms=MECL1; OS Homo sapiens (Human) PSMB10 MECL1 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit is part of the immunoproteasome where it displaces the equivalent houskeeping subunit PSMB7. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). INDUCTION: By interferon gamma. SIMILARITY: Belongs to the peptidase T1B family. UniProt P40306 Reactome DB_ID: 68806 1 UniProt:P51665 RecName: Full=26S proteasome non-ATPase regulatory subunit 7; AltName: Full=26S proteasome regulatory subunit rpn8; AltName: Full=26S proteasome regulatory subunit S12; AltName: Full=Proteasome subunit p40; AltName: Full=Mov34 protein homolog; GN Name=PSMD7; Synonyms=MOV34L; OS Homo sapiens (Human) MOV34L PSMD7 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357659, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357659, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357659, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357659, EBI-359701; SIMILARITY: Belongs to the peptidase M67A family. SIMILARITY: Contains 1 MPN (JAB/Mov34) domain. SEQUENCE CAUTION: Sequence=AAH00338.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; UniProt P51665 Reactome DB_ID: 68747 1 UniProt:P49720 RecName: Full=Proteasome subunit beta type-3; EC=3.4.25.1; AltName: Full=Proteasome theta chain; AltName: Full=Proteasome chain 13; AltName: Full=Proteasome component C10-II; GN Name=PSMB3; OS Homo sapiens (Human) PSMB3 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: Q6XUX3:RIPK5; NbExp=1; IntAct=EBI-603340, EBI-1049520; P40337:VHL; NbExp=1; IntAct=EBI-603340, EBI-301246; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt P49720 Reactome DB_ID: 68812 1 UniProt:Q06323 RecName: Full=Proteasome activator complex subunit 1; AltName: Full=Proteasome activator 28 subunit alpha; Short=PA28alpha; Short=PA28a; AltName: Full=Activator of multicatalytic protease subunit 1; AltName: Full=11S regulator complex subunit alpha; Short=REG-alpha; AltName: Full=Interferon gamma up-regulated I-5111 protein; Short=IGUP I-5111; GN Name=PSME1; Synonyms=IFI5111; OS Homo sapiens (Human) PSME1 IFI5111 FUNCTION: 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 hexadimeric ring. PSME1 can form homoheptamers. INDUCTION: By interferon gamma. SIMILARITY: Belongs to the PA28 family. UniProt Q06323 Reactome DB_ID: 68814 1 UniProt:Q9UL46 RecName: Full=Proteasome activator complex subunit 2; AltName: Full=Proteasome activator 28 subunit beta; Short=PA28beta; Short=PA28b; AltName: Full=Activator of multicatalytic protease subunit 2; AltName: Full=11S regulator complex subunit beta; Short=REG-beta; GN Name=PSME2; OS Homo sapiens (Human) PSME2 FUNCTION: 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 hexadimeric ring. INDUCTION: By interferon gamma. SIMILARITY: Belongs to the PA28 family. UniProt Q9UL46 Reactome DB_ID: 68808 1 UniProt:P48556 RecName: Full=26S proteasome non-ATPase regulatory subunit 8; AltName: Full=26S proteasome regulatory subunit S14; AltName: Full=p31; GN Name=PSMD8; OS Homo sapiens (Human) PSMD8 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. Necessary for activation of the CDC28 kinase. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-359304, EBI-1056358; Q15008:PSMD6; NbExp=1; IntAct=EBI-359304, EBI-359701; SIMILARITY: Belongs to the proteasome subunit S14 family. UniProt P48556 Reactome DB_ID: 68726 1 UniProt:P25787 RecName: Full=Proteasome subunit alpha type-2; EC=3.4.25.1; AltName: Full=Proteasome component C3; AltName: Full=Macropain subunit C3; AltName: Full=Multicatalytic endopeptidase complex subunit C3; GN Name=PSMA2; Synonyms=PSC3; OS Homo sapiens (Human) PSMA2 PSC3 FUNCTION: 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. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: O60921:HUS1; NbExp=1; IntAct=EBI-603262, EBI-1056174; P22392:NME2; NbExp=1; IntAct=EBI-603262, EBI-713693; P25789:PSMA4; NbExp=3; IntAct=EBI-603262, EBI-359310; O14818:PSMA7; NbExp=1; IntAct=EBI-603262, EBI-603272; Q15008:PSMD6; NbExp=1; IntAct=EBI-603262, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. PTM: Phosphorylated on tyrosine residues; which may be important for nuclear import (By similarity). SIMILARITY: Belongs to the peptidase T1A family. UniProt P25787 Reactome DB_ID: 68750 1 UniProt:P28070 RecName: Full=Proteasome subunit beta type-4; Short=Proteasome beta chain; EC=3.4.25.1; AltName: Full=Macropain beta chain; AltName: Full=Multicatalytic endopeptidase complex beta chain; AltName: Full=Proteasome chain 3; AltName: Full=HSN3; AltName: Full=HsBPROS26; Flags: Precursor; GN Name=PSMB4; OS Homo sapiens (Human) PSMB4 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). SIMILARITY: Belongs to the peptidase T1B family. UniProt P28070 Reactome DB_ID: 68802 1 UniProt:Q16401 RecName: Full=26S proteasome non-ATPase regulatory subunit 5; AltName: Full=26S proteasome subunit S5B; AltName: Full=26S protease subunit S5 basic; GN Name=PSMD5; Synonyms=KIAA0072; OS Homo sapiens (Human) KIAA0072 PSMD5 FUNCTION: Belongs to the 26S multisubunit protease, which is required for ubiquitin-dependent proteolysis. Does not bind ubiquitin polymers. SUBUNIT: 26S protease is composed of a multicatalytic protease (proteasome) and a regulatory ATPase complex. Both are multisubunit structures that associate in the presence of ATP to form the protease. Subunit S5B is part of the regulatory complex. DOMAIN: Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins. SIMILARITY: Belongs to the proteasome subunit S5B family. UniProt Q16401 Reactome DB_ID: 68732 1 UniProt:P28066 RecName: Full=Proteasome subunit alpha type-5; EC=3.4.25.1; AltName: Full=Proteasome zeta chain; AltName: Full=Macropain zeta chain; AltName: Full=Multicatalytic endopeptidase complex zeta chain; GN Name=PSMA5; OS Homo sapiens (Human) PSMA5 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. PSMA5 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly. INTERACTION: P25789:PSMA4; NbExp=1; IntAct=EBI-355475, EBI-359310; O14818:PSMA7; NbExp=1; IntAct=EBI-355475, EBI-603272; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1A family. UniProt P28066 Reactome DB_ID: 68738 1 UniProt:P20618 RecName: Full=Proteasome subunit beta type-1; EC=3.4.25.1; AltName: Full=Proteasome component C5; AltName: Full=Macropain subunit C5; AltName: Full=Multicatalytic endopeptidase complex subunit C5; AltName: Full=Proteasome gamma chain; Flags: Precursor; GN Name=PSMB1; Synonyms=PSC5; OS Homo sapiens (Human) PSMB1 PSC5 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: P49662:CASP4; NbExp=1; IntAct=EBI-372273, EBI-1057327; Q8IU60:DCP2; NbExp=1; IntAct=EBI-372273, EBI-521577; Q96RG2:PASK; NbExp=1; IntAct=EBI-372273, EBI-1042651; O14730:RIOK3; NbExp=1; IntAct=EBI-372273, EBI-1047061; Q6XUX3:RIPK5; NbExp=1; IntAct=EBI-372273, EBI-1049520; P40337:VHL; NbExp=1; IntAct=EBI-372273, EBI-301246; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt P20618 Reactome DB_ID: 68734 1 UniProt:P60900 RecName: Full=Proteasome subunit alpha type-6; EC=3.4.25.1; AltName: Full=Proteasome iota chain; AltName: Full=Macropain iota chain; AltName: Full=Multicatalytic endopeptidase complex iota chain; AltName: Full=27 kDa prosomal protein; AltName: Full=PROS-27; AltName: Full=p27K; GN Name=PSMA6; Synonyms=PROS27; OS Homo sapiens (Human) PSMA6 PROS27 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: P25788:PSMA3; NbExp=1; IntAct=EBI-357793, EBI-348380; P25789:PSMA4; NbExp=1; IntAct=EBI-357793, EBI-359310; O14818:PSMA7; NbExp=3; IntAct=EBI-357793, EBI-603272; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1A family. UniProt P60900 Reactome DB_ID: 68800 1 UniProt:P55036-1 RecName: Full=26S proteasome non-ATPase regulatory subunit 4; AltName: Full=26S proteasome regulatory subunit S5A; AltName: Full=Rpn10; AltName: Full=Multiubiquitin chain-binding protein; AltName: Full=Antisecretory factor 1; Short=ASF; Short=AF; GN Name=PSMD4; Synonyms=MCB1; OS Homo sapiens (Human) PSMD4 MCB1 FUNCTION: Binds and presumably selects ubiquitin-conjugates for destruction. Displays selectivity for longer polyubiquitin chains. Modulates intestinal fluid secretion. SUBUNIT: The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively. Directly interacts with NUB1. Interacts with SQSTM1. INTERACTION: P41134:ID1; NbExp=1; IntAct=EBI-359318, EBI-1215527; P24610:Pax3 (xeno); NbExp=1; IntAct=EBI-359318, EBI-1208116; O75832:PSMD10; NbExp=1; IntAct=EBI-359318, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-359318, EBI-359701; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist; Name=Rpn10A; IsoId=P55036-1; Sequence=Displayed; Name=Rpn10E; IsoId=P55036-2; Sequence=VSP_005291, VSP_005292; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay; DOMAIN: The 2 UIM motifs are involved in the binding to a multi- ubiquitin chain in a cooperative way. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. SIMILARITY: Belongs to the proteasome subunit S5A family. SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats. SIMILARITY: Contains 1 VWFA domain. UniProt P55036 Reactome DB_ID: 68794 1 UniProt:Q9UNM6 RecName: Full=26S proteasome non-ATPase regulatory subunit 13; AltName: Full=26S proteasome regulatory subunit S11; AltName: Full=26S proteasome regulatory subunit p40.5; GN Name=PSMD13; OS Homo sapiens (Human) PSMD13 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the PA700 complex. INTERACTION: P43686:PSMC4; NbExp=1; IntAct=EBI-356070, EBI-743997; Q15008:PSMD6; NbExp=1; IntAct=EBI-356070, EBI-359701; P40337:VHL; NbExp=1; IntAct=EBI-356070, EBI-301246; SIMILARITY: Belongs to the proteasome subunit S11 family. SIMILARITY: Contains 1 PCI domain. UniProt Q9UNM6 Reactome DB_ID: 68777 1 UniProt:P43686-1 RecName: Full=26S protease regulatory subunit 6B; AltName: Full=Proteasome 26S subunit ATPase 4; AltName: Full=MB67-interacting protein; AltName: Full=MIP224; AltName: Full=TAT-binding protein 7; Short=TBP-7; GN Name=PSMC4; Synonyms=MIP224, TBP7; OS Homo sapiens (Human) PSMC4 TBP7 MIP224 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. SUBUNIT: Interacts with NR1I3. Interacts with PAAF1. INTERACTION: O95816:BAG2; NbExp=1; IntAct=EBI-743997, EBI-355275; Q69YQ9:CMYA5; NbExp=1; IntAct=EBI-743997, EBI-1046610; P28566:HTR1E; NbExp=1; IntAct=EBI-743997, EBI-1043151; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-743997, EBI-1056358; P22234:PAICS; NbExp=1; IntAct=EBI-743997, EBI-712261; P62191:PSMC1; NbExp=1; IntAct=EBI-743997, EBI-357598; P35998:PSMC2; NbExp=1; IntAct=EBI-743997, EBI-359710; P17980:PSMC3; NbExp=1; IntAct=EBI-743997, EBI-359720; P62195:PSMC5; NbExp=1; IntAct=EBI-743997, EBI-357745; Q99460:PSMD1; NbExp=1; IntAct=EBI-743997, EBI-357874; O75832:PSMD10; NbExp=2; IntAct=EBI-743997, EBI-752185; O00231:PSMD11; NbExp=1; IntAct=EBI-743997, EBI-357816; Q9UNM6:PSMD13; NbExp=1; IntAct=EBI-743997, EBI-356070; Q13200:PSMD2; NbExp=1; IntAct=EBI-743997, EBI-357648; Q15008:PSMD6; NbExp=1; IntAct=EBI-743997, EBI-359701; P51665:PSMD7; NbExp=1; IntAct=EBI-743997, EBI-357659; O14730:RIOK3; NbExp=1; IntAct=EBI-743997, EBI-1047061; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P43686-1; Sequence=Displayed; Name=2; IsoId=P43686-2; Sequence=VSP_000022; Note=No experimental confirmation available; PTM: The N-terminus is blocked. SIMILARITY: Belongs to the AAA ATPase family. UniProt P43686 Reactome DB_ID: 68798 1 UniProt:O43242 RecName: Full=26S proteasome non-ATPase regulatory subunit 3; Short=26S proteasome regulatory subunit S3; AltName: Full=Proteasome subunit p58; GN Name=PSMD3; OS Homo sapiens (Human) PSMD3 FUNCTION: Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively. INTERACTION: Q9BUV8:C20orf24; NbExp=1; IntAct=EBI-357622, EBI-1050079; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357622, EBI-1056358; O75832:PSMD10; NbExp=1; IntAct=EBI-357622, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357622, EBI-359701; O75365:PTP4A3; NbExp=1; IntAct=EBI-357622, EBI-1043866; Q9P2S5:WDR8; NbExp=1; IntAct=EBI-357622, EBI-1054904; SIMILARITY: Belongs to the proteasome subunit S3 family. SIMILARITY: Contains 1 PCI domain. UniProt O43242 Reactome DB_ID: 68756 1 UniProt:P28072 RecName: Full=Proteasome subunit beta type-6; EC=3.4.25.1; AltName: Full=Proteasome delta chain; AltName: Full=Macropain delta chain; AltName: Full=Multicatalytic endopeptidase complex delta chain; AltName: Full=Proteasome subunit Y; Flags: Precursor; GN Name=PSMB6; Synonyms=LMPY; OS Homo sapiens (Human) PSMB6 LMPY FUNCTION: 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. May catalyze basal processing of intracellular antigens. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit can be displaced by the equivalent immune-specific subunit PSMB9. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt P28072 Reactome DB_ID: 68759 1 UniProt:Q99436 RecName: Full=Proteasome subunit beta type-7; EC=3.4.25.1; AltName: Full=Proteasome subunit Z; AltName: Full=Macropain chain Z; AltName: Full=Multicatalytic endopeptidase complex chain Z; Flags: Precursor; GN Name=PSMB7; OS Homo sapiens (Human) PSMB7 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit can be displaced by the equivalent immune-specific subunit PSMB10. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the peptidase T1B family. UniProt Q99436 Reactome DB_ID: 68790 1 UniProt:O00231 RecName: Full=26S proteasome non-ATPase regulatory subunit 11; AltName: Full=26S proteasome regulatory subunit S9; AltName: Full=26S proteasome regulatory subunit p44.5; GN Name=PSMD11; OS Homo sapiens (Human) PSMD11 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the PA700 complex. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357816, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357816, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357816, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357816, EBI-359701; SIMILARITY: Belongs to the proteasome subunit S9 family. SIMILARITY: Contains 1 PCI domain. UniProt O00231 Reactome DB_ID: 68810 1 UniProt:O00233-1 RecName: Full=26S proteasome non-ATPase regulatory subunit 9; AltName: Full=26S proteasome regulatory subunit p27; GN Name=PSMD9; OS Homo sapiens (Human) PSMD9 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Subunit of the modulator trimer complex that stimulates the association of the PA700 regulator with the catalytic 20S proteasome to form the ATP-dependent active 26S proteasome. P27 is associated not only with the modulator complex but also significantly with the 26S proteasome complex. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=p27-L; IsoId=O00233-1; Sequence=Displayed; Name=p27-S; IsoId=O00233-2; Sequence=VSP_005300; TISSUE SPECIFICITY: Expressed in all tissues tested, highly expressed in liver and kidney. SIMILARITY: Belongs to the proteasome subunit p27 family. SIMILARITY: Contains 1 PDZ (DHR) domain. UniProt O00233 Reactome DB_ID: 68786 1 UniProt:Q99460-1 RecName: Full=26S proteasome non-ATPase regulatory subunit 1; AltName: Full=26S proteasome regulatory subunit RPN2; AltName: Full=26S proteasome regulatory subunit S1; AltName: Full=26S proteasome subunit p112; GN Name=PSMD1; OS Homo sapiens (Human) PSMD1 FUNCTION: Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Interacts with ADRM1. INTERACTION: P30480:HLA-B; NbExp=1; IntAct=EBI-357874, EBI-1054175; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357874, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357874, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357874, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357874, EBI-359701; ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q99460-1; Sequence=Displayed; Name=2; IsoId=Q99460-2; Sequence=VSP_011475; Note=No experimental confirmation available; SIMILARITY: Belongs to the proteasome subunit S1 family. SIMILARITY: Contains 10 PC repeats. SEQUENCE CAUTION: Sequence=AAH01053.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH14013.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH39845.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH47897.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH64398.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH73833.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; UniProt Q99460 Reactome DB_ID: 68728 1 UniProt:P25788-1 RecName: Full=Proteasome subunit alpha type-3; EC=3.4.25.1; AltName: Full=Proteasome component C8; AltName: Full=Macropain subunit C8; AltName: Full=Multicatalytic endopeptidase complex subunit C8; GN Name=PSMA3; Synonyms=PSC8; OS Homo sapiens (Human) PSC8 PSMA3 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: P48634:BAT2; NbExp=1; IntAct=EBI-348380, EBI-347545; P25789:PSMA4; NbExp=1; IntAct=EBI-348380, EBI-359310; P60900:PSMA6; NbExp=1; IntAct=EBI-348380, EBI-357793; O14818:PSMA7; NbExp=1; IntAct=EBI-348380, EBI-603272; Q9H0D6:XRN2; NbExp=1; IntAct=EBI-348380, EBI-372110; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P25788-1; Sequence=Displayed; Name=2; IsoId=P25788-2; Sequence=VSP_005280; Note=No experimental confirmation available; SIMILARITY: Belongs to the peptidase T1A family. UniProt P25788 Reactome DB_ID: 68788 1 UniProt:O75832 RecName: Full=26S proteasome non-ATPase regulatory subunit 10; AltName: Full=26S proteasome regulatory subunit p28; AltName: Full=Gankyrin; GN Name=PSMD10; OS Homo sapiens (Human) PSMD10 FUNCTION: Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. SUBUNIT: Component of the PA700 complex. INTERACTION: O60496:DOK2; NbExp=1; IntAct=EBI-752185, EBI-1046024; Q9BW60:ELOVL1; NbExp=1; IntAct=EBI-752185, EBI-1050331; P62807:HIST1H2BC; NbExp=1; IntAct=EBI-752185, EBI-354552; P43358:MAGEA4; NbExp=4; IntAct=EBI-752185, EBI-743122; Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-752185, EBI-1056358; P62191:PSMC1; NbExp=1; IntAct=EBI-752185, EBI-357598; P35998:PSMC2; NbExp=1; IntAct=EBI-752185, EBI-359710; P17980:PSMC3; NbExp=1; IntAct=EBI-752185, EBI-359720; P43686:PSMC4; NbExp=2; IntAct=EBI-752185, EBI-743997; P62195:PSMC5; NbExp=1; IntAct=EBI-752185, EBI-357745; P62333:PSMC6; NbExp=1; IntAct=EBI-752185, EBI-357669; Q99460:PSMD1; NbExp=1; IntAct=EBI-752185, EBI-357874; O00231:PSMD11; NbExp=1; IntAct=EBI-752185, EBI-357816; O00232:PSMD12; NbExp=1; IntAct=EBI-752185, EBI-359733; Q13200:PSMD2; NbExp=1; IntAct=EBI-752185, EBI-357648; O43242:PSMD3; NbExp=1; IntAct=EBI-752185, EBI-357622; P55036:PSMD4; NbExp=1; IntAct=EBI-752185, EBI-359318; Q15008:PSMD6; NbExp=1; IntAct=EBI-752185, EBI-359701; P51665:PSMD7; NbExp=1; IntAct=EBI-752185, EBI-357659; P06400:RB1; NbExp=1; IntAct=EBI-752185, EBI-491274; SIMILARITY: Contains 7 ANK repeats. UniProt O75832 Reactome DB_ID: 68762 1 UniProt:P28062-1 RecName: Full=Proteasome subunit beta type-8; EC=3.4.25.1; AltName: Full=Proteasome subunit beta-5i; AltName: Full=Proteasome component C13; AltName: Full=Macropain subunit C13; AltName: Full=Multicatalytic endopeptidase complex subunit C13; Flags: Precursor; GN Name=PSMB8; Synonyms=LMP7, RING10, Y2; OS Homo sapiens (Human) Y2 LMP7 RING10 PSMB8 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. This subunit is part of the immunoproteasome where it displaces the equivalent housekeeping subunit PSMB5. Directly interacts with POMP (By similarity). INTERACTION: O15116:LSM1; NbExp=1; IntAct=EBI-372294, EBI-347619; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist; Name=1; Synonyms=LMP7B, LMP7-E2; IsoId=P28062-1; Sequence=Displayed; Name=2; Synonyms=LMP7A, LMP7-E1; IsoId=P28062-2; Sequence=VSP_005287; SIMILARITY: Belongs to the peptidase T1B family. UniProt P28062 Reactome DB_ID: 68768 1 UniProt:P62191 RecName: Full=26S protease regulatory subunit 4; AltName: Full=P26s4; AltName: Full=Proteasome 26S subunit ATPase 1; GN Name=PSMC1; OS Homo sapiens (Human) PSMC1 FUNCTION: The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. SUBUNIT: Interacts with SCA7. Interacts with NGLY1. Interacts with PAAF1. INTERACTION: Q9BRP4:PAAF1; NbExp=1; IntAct=EBI-357598, EBI-1056358; P43686:PSMC4; NbExp=1; IntAct=EBI-357598, EBI-743997; O75832:PSMD10; NbExp=1; IntAct=EBI-357598, EBI-752185; Q15008:PSMD6; NbExp=1; IntAct=EBI-357598, EBI-359701; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. SIMILARITY: Belongs to the AAA ATPase family. UniProt P62191 Reactome DB_ID: 68724 1 UniProt:P25786-1 RecName: Full=Proteasome subunit alpha type-1; EC=3.4.25.1; AltName: Full=Proteasome component C2; AltName: Full=Macropain subunit C2; AltName: Full=Multicatalytic endopeptidase complex subunit C2; AltName: Full=Proteasome nu chain; AltName: Full=30 kDa prosomal protein; AltName: Full=PROS-30; GN Name=PSMA1; Synonyms=PROS30, PSC2; OS Homo sapiens (Human) PSMA1 PROS30 PSC2 FUNCTION: 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. CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity. 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. INTERACTION: P25789:PSMA4; NbExp=1; IntAct=EBI-359352, EBI-359310; O14818:PSMA7; NbExp=3; IntAct=EBI-359352, EBI-603272; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=Short; IsoId=P25786-1; Sequence=Displayed; Name=Long; IsoId=P25786-2; Sequence=VSP_005279; SIMILARITY: Belongs to the peptidase T1A family. UniProt P25786 Reactome 68819 Database 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=68819 Reactome REACT_2353 1 Reactome 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=REACT_2353.1 GO 0004175 GO molecular function Reactome 68824 Database 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=68824 Reactome 195298 Database 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=195298 Reactome REACT_10017 1 Reactome 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=REACT_10017.1 17183061 Pubmed 2006 Docosahexaenoic Acid Induces Proteasome-dependent Degradation of {beta}-catenin, Down-regulation of Survivin and Apoptosis in Human Colorectal Cancer Cells not expressing COX-2 Calviello, G Resci, F Serini, S Piccioni, E Toesca, A Boninsegna, A Monego, G Ranelletti, FO Palozza, P Carcinogenesis Reactome 195253 Database 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=195253 Reactome REACT_11063 1 Reactome 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=REACT_11063.1 Reactome 195721 Database 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=195721 Reactome REACT_11045 1 Reactome 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=REACT_11045.1