BioPAX pathway converted from "UCH proteinases" in the Reactome database.

UCH proteinases

This event has been computationally inferred from an event that has been demonstrated in another species.The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>

ADRM1 binds 26S proteasome

Reactome DB_ID: 9786824

cytosolGO0005829

UniProt:Q9JKV1Adrm1

Reactomehttp://www.reactome.orgMus musculus

NCBI Taxonomy10090UniProtQ9JKV1

Chain Coordinates

EQUAL

407

EQUAL

Reactome DB_ID: 9707655

26S proteasome [cytosol]

26S proteasome

Reactome DB_ID: 9707621

UniProt:Q9CX56Psmd8

UniProtQ9CX56

EQUAL

350

EQUAL

Reactome DB_ID: 9707561

UniProt:O88685Psmc3

UniProtO88685

EQUAL

439

EQUAL

Reactome DB_ID: 9707651

UniProt:Q8BG41 Psmb11

Psmb11

Psmb11FUNCTION 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. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome. Plays a pivotal role in development of CD8-positive T-cells.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. Incorporated instead of PSMB5 and PSMB8.TISSUE SPECIFICITY Expressed exclusively in cortical thymic epithelial cells.DISRUPTION PHENOTYPE Displays defective development of CD8-positive T-cells in the thymus.SIMILARITY Belongs to the peptidase T1B family.

UniProtQ8BG41

EQUAL

300

EQUAL

Reactome DB_ID: 9707536

UniProt:O09061 Psmb1

Psmb1

Psmb1FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with SERPINB2 (By similarity). Interacts with RFPL4A (PubMed:12525704).TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtO09061

EQUAL

241

EQUAL

Reactome DB_ID: 9707585

UniProt:Q8BG32Psmd11

UniProtQ8BG32

EQUAL

422

EQUAL

Reactome DB_ID: 9707593

UniProt:Q9WVJ2Psmd13

UniProtQ9WVJ2

EQUAL

376

EQUAL

Reactome DB_ID: 9707648

UniProt:Q9CWH6 Psma8

Psma8

Psma7lPsma8FUNCTION Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis (PubMed:23706739, PubMed:31358751, PubMed:31437213). The proteasome is a protein complexe that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds (Probable). Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis (PubMed:31358751). Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I (PubMed:31437213).SUBUNIT Component of the outer alpha-ring of the 20S proteasome core which is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure (PubMed:23706739, PubMed:31358751). The catalytic chamber with the active sites is on the inside of the barrel (Probable). Interacts with canonical subunits of the spermatoproteasome, including proteasome activators PSME4 (also called PA200) and PSME3 (also called PA28-gamma) (PubMed:31437213). Interacts with proteasome-interacting proteins chaperones including CCT6B and CCT2, ubiquitin ligases (TRIP12, NEDD4, TRIM36 and RAD18), and ubiquitin specific proteases such as USP9X, USP34, USP5 and USP47 (PubMed:31437213). Interacts with meiotic proteins cyclin dependent kinase CDK1 and the ATPase TRIP13 as well as proteins of the synaptonemal complex SIX6OS1 and SYCE3 (PubMed:31437213).DEVELOPMENTAL STAGE In testes, expressed in spermatocytes at the pachytene stage (weakly in early pachynema and strongly in late pachynema), and its expression persisted thereafter throughout spermatogenesis.DISRUPTION PHENOTYPE Knockout mice were obtained according to the expected Mendelian ratios and showed no obvious phenotypes with respect to viability and development; however males show infertility (PubMed:31358751, PubMed:31437213). PSMA8-null spermatocytes exhibit delayed M-phase entry and are finally arrested at this stage, resulting in male infertility (PubMed:31358751, PubMed:31437213).SIMILARITY Belongs to the peptidase T1A family.CAUTION Predicted to have endopeptidase activity (By similarity). However, as it is located in the outer alpha-ring, it is suggested to lack catalytic activity and preferentially interact with regulatory complexes such as PSME4/PA200.

UniProtQ9CWH6

EQUAL

256

EQUAL

Reactome DB_ID: 9707543

UniProt:O55234 Psmb5

Psmb5

Psmb5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Directly interacts with POMP (By similarity). Interacts with ABCB1 and TAP1 (By similarity).TISSUE SPECIFICITY Expressed in uterus at the embryo implantation site.INDUCTION Up-regulated in embryonic fibroblasts and neuroblastoma cells by antioxidants through the Nrf2-ARE pathway (at protein level). Up-regulated by the antioxidant dithiolethione (D3T) in liver, small intestine and brain (at protein level). Down-regulated under lithium treatment.SIMILARITY Belongs to the peptidase T1B family.

UniProtO55234

EQUAL

263

EQUAL

Reactome DB_ID: 1236795

UniProt:Q9R1P1 Psmb3

Psmb3

Psmb3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtQ9R1P1

EQUAL

205

EQUAL

Reactome DB_ID: 9707581

UniProt:Q9Z2X2Psmd10

UniProtQ9Z2X2

EQUAL

226

EQUAL

Reactome DB_ID: 1236775

UniProt:P70195 Psmb7

Psmb7

Psmb7Mmc14FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.INDUCTION Up-regulated by the antioxidant dithiolethione (D3T) in colon (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtP70195

EQUAL

277

EQUAL

Reactome DB_ID: 1236823

UniProt:Q9QUM9 Psma6

Psma6

Psma6FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with ALKBH4 (By similarity).TISSUE SPECIFICITY Detected in liver (at protein level).INDUCTION Up-regulated in liver tumor tissues (at protein level).SIMILARITY Belongs to the peptidase T1A family.

UniProtQ9QUM9

EQUAL

246

EQUAL

Reactome DB_ID: 9707637

UniProt:P61290Psme3

UniProtP61290

EQUAL

254

EQUAL

Reactome DB_ID: 9707569

UniProt:P62196Psmc5

UniProtP62196

EQUAL

406

EQUAL

Reactome DB_ID: 9707565

UniProt:P54775Psmc4

UniProtP54775

EQUAL

418

EQUAL

Reactome DB_ID: 9707553

UniProt:P62192Psmc1

UniProtP62192

EQUAL

440

EQUAL

Reactome DB_ID: 9707613

UniProt:Q99JI4Psmd6

UniProtQ99JI4

EQUAL

389

EQUAL

Reactome DB_ID: 1236812

UniProt:P99026 Psmb4

Psmb4

Lmp3Psmb4FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Forms a ternary complex with SMAD1 and OAZ1 before PSMB4 is incorporated into the 20S proteasome (By similarity). Interacts with PRPF19 (By similarity).TISSUE SPECIFICITY Detected in liver (at protein level).INDUCTION Up-regulated in liver tumor tissues (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtP99026

EQUAL

264

EQUAL

Reactome DB_ID: 1236800

UniProt:P49722 Psma2

Psma2

Psma2Lmpc3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.TISSUE SPECIFICITY Detected in liver (at protein level).PTM Phosphorylated on tyrosine residues; which may be important for nuclear import.SIMILARITY Belongs to the peptidase T1A family.

UniProtP49722

EQUAL

234

EQUAL

Reactome DB_ID: 1236802

UniProt:Q9R1P4 Psma1

Psma1

Psma1FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966). Interacts with NOTCH3 (By similarity). Interacts with ZFAND1 (By similarity).TISSUE SPECIFICITY Detected in liver (at protein level).INDUCTION Up-regulated in liver tumor tissues. Up-regulated by the antioxidant dithiolethione (D3T) in liver, lung and colon (at the protein level).PTM C-terminal extension is partially cleaved off by limited proteolysis leading to a conversion of the proteasome from its latent into its active form.SIMILARITY Belongs to the peptidase T1A family.

UniProtQ9R1P4

EQUAL

263

EQUAL

Reactome DB_ID: 9707609

UniProt:Q8BJY1Psmd5

UniProtQ8BJY1

EQUAL

504

EQUAL

Reactome DB_ID: 9707524

UniProt:O35593Psmd14

UniProtO35593

EQUAL

310

EQUAL

Reactome DB_ID: 9707546

UniProt:Q60692 Psmb6

Psmb6

Psmb6Lmp19FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolyzing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.INDUCTION Up-regulated by the antioxidant dithiolethione (D3T) in liver, lung and small intestine (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtQ60692

EQUAL

239

EQUAL

Reactome DB_ID: 1236811

UniProt:O35955 Psmb10

Psmb10

Psmb10Lmp10Mecl1FUNCTION 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. Plays a role in determining the T-cell repertoire for an antiviral T-cell response.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB7. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.TISSUE SPECIFICITY Detected in liver (at protein level).INDUCTION Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.DISRUPTION PHENOTYPE Impaired response of cytotoxic T-lymphocyte (CTL) to dominant epitopes of lymphocytic choriomeningitis virus (LCMV).SIMILARITY Belongs to the peptidase T1B family.

UniProtO35955

EQUAL

273

EQUAL

Reactome DB_ID: 9707573

UniProt:P62334Psmc6

UniProtP62334

EQUAL

389

EQUAL

Reactome DB_ID: 9707605

UniProt:O35226Psmd4

UniProtO35226

EQUAL

377

EQUAL

Reactome DB_ID: 9707641

UniProt:Q8BHL8Psmf1

UniProtQ8BHL8

EQUAL

271

EQUAL

Reactome DB_ID: 1236877

UniProt:Q9Z2U1 Psma5

Psma5

Psma5FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). PSMA5 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (By similarity).TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1A family.

UniProtQ9Z2U1

EQUAL

241

EQUAL

Reactome DB_ID: 1236868

UniProt:O70435 Psma3

Psma3

Psma3FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with AURKB. Interacts with CDKN1A. Interacts with MDM2 and RB1. Interacts with the C-terminus of TBXA2R isoform 2. Interacts with DNAJB2.TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1A family.

UniProtO70435

EQUAL

255

EQUAL

Reactome DB_ID: 1236864

UniProt:P28063 Psmb8

Psmb8

Lmp7Mc13Psmb8FUNCTION 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. May participate in the inflammatory response pathway. Required for adipocyte differentiation (PubMed:21881205, PubMed:22341445, PubMed:8066463). May be involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (By similarity).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1.TISSUE SPECIFICITY Detected in liver (at protein level). Expressed in spleen, thymus, lung, liver, heart and, at a very low level, in kidney. Not expressed in brain nor testis.INDUCTION Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Down-regulated in spleen by deoxynivalenol (DON), a mycotoxin that alters immune functions. Down-regulated by the selective inhibitor PR-957. Up-regulated by heat shock treatment. Down-regulated by EGR1 in neuronal cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.POLYMORPHISM The allele, LMP7k/LMP7s/LMPf/LMP7r/LMPcas4/LMPg7 found in strains NMRI, B10.BR, SJL, A.CA, B10.RIII, B10.cas4 and NOD may be post-translationally modified. Allele LMP7q is found in strain DBA/1J.SIMILARITY Belongs to the peptidase T1B family.

UniProtP28063

EQUAL

276

EQUAL

Reactome DB_ID: 9707533

UniProt:Q9Z2U0 Psma7

Psma7

Psma7FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (By similarity). Interacts with HIF1A (By similarity). Interacts with RAB7A (By similarity). Interacts with PRKN (By similarity). Interacts with ABL1 and ABL2 (By similarity). Interacts with EMAP2 (By similarity). Interacts with MAVS (By similarity).TISSUE SPECIFICITY Detected in liver (at protein level).INDUCTION Up-regulated in liver tumor tissues.PTM Phosphorylation by ABL1 or ABL2 leads to an inhibition of proteasomal activity and cell cycle transition blocks.SIMILARITY Belongs to the peptidase T1A family.

UniProtQ9Z2U0

EQUAL

248

EQUAL

Reactome DB_ID: 9707617

UniProt:P26516Psmd7

UniProtP26516

EQUAL

324

EQUAL

Reactome DB_ID: 9707601

UniProt:P14685Psmd3

UniProtP14685

EQUAL

534

EQUAL

Reactome DB_ID: 9707633

UniProt:P97372Psme2

UniProtP97372

EQUAL

239

EQUAL

Reactome DB_ID: 9707557

UniProt:P46471Psmc2

UniProtP46471

EQUAL

433

EQUAL

Reactome DB_ID: 1236839

UniProt:Q9R1P0 Psma4

Psma4

Psma4FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445).TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1A family.

UniProtQ9R1P0

EQUAL

261

EQUAL

Reactome DB_ID: 9707645

UniProt:Q5SSW2Psme4

UniProtQ5SSW2

EQUAL

1843

EQUAL

Reactome DB_ID: 1236756

UniProt:Q9R1P3 Psmb2

Psmb2

Psmb2FUNCTION Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.TISSUE SPECIFICITY Detected in liver (at protein level).SIMILARITY Belongs to the peptidase T1B family.

UniProtQ9R1P3

EQUAL

201

EQUAL

Reactome DB_ID: 9707629

UniProt:P97371Psme1

UniProtP97371

EQUAL

249

EQUAL

Reactome DB_ID: 9707625

UniProt:Q9CR00Psmd9

UniProtQ9CR00

EQUAL

223

EQUAL

Reactome DB_ID: 9707577

UniProt:Q3TXS7Psmd1

UniProtQ3TXS7

EQUAL

953

EQUAL

Reactome DB_ID: 9707589

UniProt:Q9D8W5Psmd12

UniProtQ9D8W5

EQUAL

456

EQUAL

Reactome DB_ID: 9707653

Ghost homologue of SHFM1 [cytosol]

Ghost homologue of SHFM1

Reactome DB_ID: 1236853

UniProt:P28076 Psmb9

Psmb9

Lmp2Ring12Psmb9FUNCTION 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. Contributes to NFKBIA degradation and subsequently NFKB1 generation.SUBUNIT The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Interacts with NCOA1, NCOA2 and NCOA3.TISSUE SPECIFICITY Detected in liver (at protein level). Expressed at high levels in the thymus, spleen, lung, heart and liver. Expressed at moderate levels in the kidney.INDUCTION Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by heat shock treatment. Down-regulated by EGR1 in neuronal cells.PTM Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.DISRUPTION PHENOTYPE Depletion of LMP2 by RNAi suppresses expression and activities of the matrix metalloproteinase MMP2 and MMP9 by blocking the transfer of active NF-kappa-B heterodimers into the nucleus.SIMILARITY Belongs to the peptidase T1B family.

UniProtP28076

EQUAL

219

EQUAL

Reactome DB_ID: 9707597

UniProt:Q8VDM4Psmd2

UniProtQ8VDM4

EQUAL

908

EQUAL

Reactome Database ID Release 759707655Database 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=9707655ReactomeR-MMU-68819

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=R-MMU-68819.1

Reactome DB_ID: 9786826

ADRM1:26S proteasome [cytosol]

ADRM1:26S proteasome

Reactome DB_ID: 9786824

EQUAL

407

EQUAL

Reactome DB_ID: 9707655

Reactome Database ID Release 759786826Database 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=9786826ReactomeR-MMU-5665858

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=R-MMU-5665858.1Reactome Database ID Release 759786853Database 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=9786853ReactomeR-MMU-5665871

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=R-MMU-5665871.1ADRM1 (also called Rpn13) interacts with the 26S proteasome base unit PRDM1 (Rpn2) via its amino-terminus and is found in the majority of 26S proteasomes. It is a receptor for Ubiquitin (Ub) that can bind K48-linked di-Ub (Schreiner et al. 2008, Husnjak et al. 2008) and de-ubiquitinating enzymes (DUBs) such as PSMD14 (Rpn11, POH1), USP14, and UCHL5 (UCH37) (Reyes-Turcu et al., 2009). Together, these DUBs disassemble poly-Ub chains and recycle ubiquitin during proteasomal degradation.

18497817Pubmed2008Proteasome subunit Rpn13 is a novel ubiquitin receptorHusnjak, KoraljkaElsasser, SuzanneZhang, NaixiaChen, XiangRandles, LeahShi, YuanHofmann, KayWalters, Kylie JFinley, DanielDikic, IvanNature 453:481-818497827Pubmed2008Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interactionSchreiner, PatrickChen, XiangHusnjak, KoraljkaRandles, LeahZhang, NaixiaElsasser, SuzanneFinley, DanielDikic, IvanWalters, Kylie JGroll, MichaelNature 453:548-5219489724Pubmed2009Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymesReyes-Turcu, Francisca EVentii, Karen HWilkinson, Keith DAnnu. Rev. Biochem. 78:363-97inferred by electronic annotationIEAGOIEA

ADRM1:26S proteaseome binds UCHL5

Reactome DB_ID: 2179301

UniProt:Q9WUP7 Uchl5

Uchl5

Uch37Uchl5FUNCTION Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1 (By similarity).ACTIVITY REGULATION Activated by ADRM1. Inhibited by interaction with NFRKB (By similarity).SUBUNIT Component of the 19S (PA700) regulatory complex of the 26S proteasome. Interacts with ADRM1 and NFRKB. Component of the INO80 complex; specifically part of a complex module associated with N-terminus of INO80 (By similarity).SIMILARITY Belongs to the peptidase C12 family.

UniProtQ9WUP7

EQUAL

329

EQUAL

Reactome DB_ID: 9786826

Reactome DB_ID: 9786828

ADRM1:26S proteasome:UCHL5 [cytosol]

ADRM1:26S proteasome:UCHL5

Reactome DB_ID: 2179301

EQUAL

329

EQUAL

Reactome DB_ID: 9786826

Reactome Database ID Release 759786828Database 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=9786828ReactomeR-MMU-5665845

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=R-MMU-5665845.1Reactome Database ID Release 759786830Database 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=9786830ReactomeR-MMU-5665854

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=R-MMU-5665854.1The C-terminal extension of UCHL5 (UCH37) binds to ADRM1, part of the proteasomal 19S regulatory subunit which is itself a subunit of the 26S proteasome. Binding of UCHL5 enhances its DUB activity (Qiu et al. 2006). UCHL5 forms oligomers in solution that have very low DUB activity. Binding with ADRM1 is 1:1, preventing oligomerization of UCHL5 while making the active site of UCHL5 accessible to Ubiquitin (Jiao et al. 2014). When associated with the proteasome, UCHL5 disassembles poly-Ub chains by hydrolyzing the distal ubiquitin from a chain. This dissassembly of the degradation signal from only the distal end of polyubiquitin chains may selectively rescue poorly ubiquitinated or slowly degraded Ub-protein conjugates from proteolysis (Lam et al. 1997).

17139257Pubmed2006hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37Qiu, XBOuyang, Song-YingLi, Chao-JunMiao, ShiyingWang, LinfangGoldberg, Alfred LEMBO J. 25:5742-5316990800Pubmed2006A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomesHamazaki, JunIemura, SNatsume, TYashiroda, HidekiTanaka, KeijiMurata, ShigeoEMBO J. 25:4524-3624752541Pubmed2014Mechanism of the Rpn13-induced activation of Uch37Jiao, LianyingOuyang, SongyingShaw, NeilSong, GaojieFeng, YingangNiu, FengfengQiu, WeichengZhu, HongtaoHung, Li-WeiZuo, XiaobingEleonora Shtykova, VZhu, PingDong, Yu-HuiXu, RuxiangLiu, Zhi-JieProtein Cell 5:616-309034192Pubmed1997Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasomeLam, Y AXu, WDeMartino, G NCohen, R ENature 385:737-40inferred by electronic annotationIEAGOIEA

UCHL5 binds INO80 complex

Reactome DB_ID: 9789982

nucleoplasmGO0005654INO80 complex [nucleoplasm]

INO80 complex

Reactome DB_ID: 9789967

UniProt:Q8BHA0Ino80c

UniProtQ8BHA0

EQUAL

192

EQUAL

Reactome DB_ID: 9789963

UniProt:Q99PT3Ino80b

UniProtQ99PT3

EQUAL

356

EQUAL

Reactome DB_ID: 9775017

UniProt:Q9Z2N8Actl6a

UniProtQ9Z2N8

EQUAL

429

EQUAL

Reactome DB_ID: 9789959

UniProt:Q8R2S9Actr8

UniProtQ8R2S9

EQUAL

624

EQUAL

Reactome DB_ID: 9789947

UniProt:Q6PIJ4Nfrkb

UniProtQ6PIJ4

EQUAL

1299

EQUAL

Reactome DB_ID: 9781529

UniProt:P60710 Actb

Actb

ActbFUNCTION Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (By similarity). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (By similarity). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:23558171, PubMed:25759381).SUBUNIT Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (PubMed:25759381). Each actin can bind to 4 others (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, MARCB1/BAF47, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3 (By similarity). Found in a complex with XPO6, Ran, ACTB and PFN1 (By similarity). Component of a complex composed at least of ACTB, AP2M1, AP2A1, AP2A2, MEGF10 and VIM (By similarity). Interacts with XPO6 and EMD (By similarity). Interacts with ERBB2 (By similarity). Interacts with GCSAM (By similarity). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with TBC1D21 (PubMed:21128978). Interacts with DHX9 (via C-terminus); this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (By similarity). Interacts with FAM107A (PubMed:21969592).TISSUE SPECIFICITY Expressed in the epididymis (at protein level) (PubMed:30659401). Expressed in the kidney (at protein level) (PubMed:31605441).PTM ISGylated.PTM Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization (PubMed:23911929). MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (PubMed:23911929).PTM Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.PTM Methylated at His-73 by SETD3 (PubMed:30626964). Methylation at His-73 is required for smooth muscle contraction of the laboring uterus during delivery (PubMed:30626964).MISCELLANEOUS In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.SIMILARITY Belongs to the actin family.

UniProtP60710

EQUAL

375

EQUAL

Reactome DB_ID: 9745686

UniProt:P60122Ruvbl1

UniProtP60122

EQUAL

456

EQUAL

Reactome DB_ID: 9789972

UniProt:Q3U1J1Tfpt

UniProtQ3U1J1

EQUAL

253

EQUAL

Reactome DB_ID: 9789955

UniProt:Q80US4Actr5

UniProtQ80US4

EQUAL

607

EQUAL

Reactome DB_ID: 9776032

UniProt:Q99L90Mcrs1

UniProtQ99L90

EQUAL

462

EQUAL

Reactome DB_ID: 9789951

UniProt:Q6ZPV2Ino80

UniProtQ6ZPV2

EQUAL

1556

EQUAL

Reactome DB_ID: 9789980

UniProt:D3Z3H0Ino80e

UniProtD3Z3H0

EQUAL

244

EQUAL

Reactome DB_ID: 9789976

UniProt:Q66JY2Ino80d

UniProtQ66JY2

EQUAL

878

EQUAL

Reactome DB_ID: 5619454

UniProt:Q00899 Yy1

Yy1

Yy1UcrbpFUNCTION Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site. Binds to the consensus sequence 5'-CCGCCATNTT-3'; some genes have been shown to contain a longer binding motif allowing enhanced binding; the initial CG dinucleotide can be methylated greatly reducing the binding affinity. The effect on transcription regulation is depending upon the context in which it binds and diverse mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression. Binds to the upstream conserved region (UCR) (5'-CGCCATTTT-3') of Moloney murine leukemia virus (MuLV). Acts synergistically with the SMAD1 and SMAD4 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (PubMed:15329343). Proposed to recruit the PRC2/EED-EZH2 complex to target genes that are transcriptional repressed. Involved in DNA repair. In vitro, binds to DNA recombination intermediate structures (Holliday junctions). Involved in spermatogenesis and may play a role in meiotic DNA double-strand break repair. Plays a role in regulating enhancer activation (By similarity).FUNCTION Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair; proposed to target the INO80 complex to YY1-responsive elements.SUBUNIT Interacts with YAF2 through the region encompassing the first and second zinc fingers. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Interacts with EED and EZH2; the interactions are indicative for an association with the PRC2/EED-EZH2 complex (By similarity). Found in a complex with SMAD1 and SMAD4 (PubMed:15329343). Interacts with SFMBT2 (PubMed:18024232). Found in a complex with YY1, SIN3A and HDAC1 (PubMed:21454521).TISSUE SPECIFICITY Expressed in ovary and, at lower levels, in testis.DEVELOPMENTAL STAGE At 7.5 dpc, highly expressed in the ectoplacental cone and, at lower levels, in the embryonic and extraembryonic ectoderm. At 14.5 dpc, highly expressed in placenta and yolk sac, and, at lower levels, in brain and heart.PTM Transiently poly-ADP-ribosylated by PARP1 upon DNA damage, with the effect of decreasing affinity of YY1 to its cognate DNA binding sites.PTM Ubiquitinated.DISRUPTION PHENOTYPE Spermatocytes have a significant decrease in the global level of the heterochromatin markers and increase in the chromosomal double-strand break (DSB) signals at the leptotene/zygotene stages.SIMILARITY Belongs to the YY transcription factor family.

UniProtQ00899

EQUAL

414

EQUAL

Reactome Database ID Release 759789982Database 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=9789982ReactomeR-MMU-5689568

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=R-MMU-5689568.1

Reactome DB_ID: 9789984

EQUAL

329

EQUAL

Reactome DB_ID: 9789986

UCHL5:INO80 complex [nucleoplasm]

UCHL5:INO80 complex

Reactome DB_ID: 9789982

Reactome DB_ID: 9789984

EQUAL

329

EQUAL

Reactome Database ID Release 759789986Database 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=9789986ReactomeR-MMU-5689602

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=R-MMU-5689602.1Reactome Database ID Release 759789988Database 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=9789988ReactomeR-MMU-5689544

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=R-MMU-5689544.1The C-terminal extension of UCHL5 (UCH37) binds NFRKB within the INO80 chromatin remodeling complex (Yao et al. 2006, 2008, Conoway & Conoway 2009).

19062292Pubmed2009The INO80 chromatin remodeling complex in transcription, replication and repairConaway, Ronald CConaway, Joan WelikyTrends Biochem. Sci. 34:71-718922472Pubmed2008Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complexYao, TingtingSong, LJin, JingjiCai, YongTakahashi, HidehisaSwanson, Selene KWashburn, Michael PFlorens, Laurence AConaway, Ronald CCohen, Robert EConaway, Joan WMol. Cell 31:909-1716906146Pubmed2006Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1Yao, TingtingSong, LXu, WeiDeMartino, George NFlorens, Laurence ASwanson, Selene KWashburn, Michael PConaway, Ronald CConaway, Joan WelikyCohen, Robert ENat. Cell Biol. 8:994-1002inferred by electronic annotationIEAGOIEA

BAP1 binds BAP1-interacting complex

Reactome DB_ID: 9789992

UniProt:Q99PU7Bap1

UniProtQ99PU7

EQUAL

729

EQUAL

Reactome DB_ID: 9790016

BAP1-interacting complex [nucleoplasm]

BAP1-interacting complex

Reactome DB_ID: 9790014

BAP1-interacting core complex [nucleoplasm]

BAP1-interacting core complex

Converted from EntitySet in Reactome

Reactome DB_ID: 9790002

ASXL1,ASXL2 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityAsxl2 [nucleoplasm]Asxl1 [nucleoplasm]

UniProtQ8BZ32UniProtP59598

Reactome DB_ID: 9776044

UniProt:Q8CGY8Ogt

UniProtQ8CGY8

EQUAL

1046

EQUAL

Reactome DB_ID: 9761007

UniProt:Q61191Hcfc1

UniProtQ61191

EQUAL

2035

EQUAL

Converted from EntitySet in Reactome

Reactome DB_ID: 9790012

FOXK1,FOXK2 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityFoxk1 [nucleoplasm]Foxk2 [nucleoplasm]

UniProtP42128UniProtQ3UCQ1Reactome Database ID Release 759790014Database 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=9790014ReactomeR-MMU-5689678

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=R-MMU-5689678.1

Reactome DB_ID: 5619454

EQUAL

414

EQUAL

Reactome Database ID Release 759790016Database 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=9790016ReactomeR-MMU-5689653

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=R-MMU-5689653.1

Reactome DB_ID: 9790018

BAP1:BAP1-interacting complex [nucleoplasm]

BAP1:BAP1-interacting complex

Reactome DB_ID: 9789992

EQUAL

729

EQUAL

Reactome DB_ID: 9790016

Reactome Database ID Release 759790018Database 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=9790018ReactomeR-MMU-5689682

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=R-MMU-5689682.1Reactome Database ID Release 759790020Database 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=9790020ReactomeR-MMU-5689630

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=R-MMU-5689630.1BRCA1-associated protein 1 (BAP1) is a ubiquitin COOH-terminal hydrolase that was initially identified as a protein that binds the RING finger domain of the breast and ovarian tumor suppressor BRCA1. BAP1 is a tumour suppressor that is believed to mediate its effects through chromatin modulation, transcriptional regulation, and possibly via the ubiquitin-proteasome system and the DNA damage response pathway (Murali et al. 2013). The C-terminal coiled coil motif of BAP1 directly interacts with the zinc fingers of the transcription factor Yin Yang 1 (YY1) (Yu et al. 2010), part of a multiprotein complex containing numerous transcription factors and cofactors including the transcriptional regulator Host cell factor 1 (HCFC1), which binds the N-terminal portion of BAP1 (Misaghi et al. 2009, Machida et al. 2009). HCFC1 is a chromatin-associated protein initially identified as part of a multiprotein complex comprising the viral coactivator VP16 and the POU domain transcription factor POU2F1. During herpes simplex virus infection, this complex is recruited to the enhancer/promoter of the immediate-early gene to activate viral gene expression (Kristie et al. 2010). The C-terminal extension of UCHL5 mediates association with Adrm1/Rpn13 of the proteasomal 19S regulatory subunit and with NFRKB of the INO80 chromatin remodeling complex. The extreme C-terminal segment of BAP1 is 38% identical to the C-terminus of UCHL5 (UCH37) and is necessary for binding to YY1 (Yu et al. 2010).

19188440Pubmed2009Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1Misaghi, ShahramOttosen, SørenIzrael-Tomasevic, AnitaArnott, DavidLamkanfi, MohamedLee, JamesLiu, JinfengO'Rourke, KarenDixit, Vishva MWilson, Angus CMol. Cell. Biol. 29:2181-9219815555Pubmed2009The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1Machida, Yuichi JMachida, YukaVashisht, Ajay AWohlschlegel, James ADutta, AnindyaJ. Biol. Chem. 284:34179-8819117993Pubmed2009BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activityNishikawa, HiroyukiWu, WenwenKoike, AyakaKojima, RyokoGomi, HiromichiFukuda, MamoruOhta, TomohikoCancer Res. 69:111-920805357Pubmed2010The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expressionYu, HelenMashtalir, NazarDaou, SalimaHammond-Martel, IanRoss, JulieSui, GuangchaoHart, Gerald WRauscher, Frank JDrobetsky, ElliotMilot, EricShi, YangAffar, El BachirMol. Cell. Biol. 30:5071-8523277170Pubmed2013Tumours associated with BAP1 mutationsMurali, RajmohanWiesner, ThomasScolyer, Richard APathology 45:116-269528852Pubmed1998BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppressionJensen, D EProctor, MMarquis, S TGardner, H PHa, S IChodosh, L AIshov, A MTommerup, NVissing, HSekido, YMinna, JBorodovsky, ASchultz, D CWilkinson, K DMaul, G GBarlev, NBerger, S LPrendergast, G CRauscher, F JOncogene 16:1097-11219682612Pubmed2010Control of alpha-herpesvirus IE gene expression by HCF-1 coupled chromatin modification activitiesKristie, Thomas MLiang, YVogel, Jodi LBiochim. Biophys. Acta 1799:257-65inferred by electronic annotationIEAGOIEA

BAP1 binds Ub-HCFC1

Reactome DB_ID: 9789992

EQUAL

729

EQUAL

Reactome DB_ID: 9790701

ubiquitinylated lysine (K48-polyUb, K63-polyUb [nucleoplasm]) at 1807 (in Homo sapiens)

1807

EQUAL

ubiquitinylated lysine [MOD:01148]

EQUAL

2035

EQUAL

Reactome DB_ID: 9790703

BAP1:K48polyUb,K63polyUb-HCFC1 [nucleoplasm]

BAP1:K48polyUb,K63polyUb-HCFC1

Reactome DB_ID: 9789992

EQUAL

729

EQUAL

Reactome DB_ID: 9790701

ubiquitinylated lysine (K48-polyUb, K63-polyUb [nucleoplasm]) at 1807 (in Homo sapiens)

1807

EQUAL

2035

EQUAL

Reactome Database ID Release 759790703Database 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=9790703ReactomeR-MMU-5690760

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=R-MMU-5690760.1Reactome Database ID Release 759790712Database 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=9790712ReactomeR-MMU-5690785

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=R-MMU-5690785.1BRCA1 associated protein 1 (BAP1) is a tumour suppressor that is believed to mediate its effects through chromatin modulation, transcriptional regulation, and possibly via the ubiquitin-proteasome system and the DNA damage response pathway (Eletr & Wilkinson 2011, Murali et al. 2013). BAP1 mediates the deubiquitination of Host cell factor 1 (HCFC1) thereby regulating cell growth, though deubiquitination of HCFC1 does not lead to increased HCFC1 stability. HCFC1 is K48 and K63 ubiquitinated. The major site of linkage are lysines 1807 and 1808 (Machida et al. 2009).

21484256Pubmed2011An emerging model for BAP1's role in regulating cell cycle progressionEletr, Ziad MWilkinson, Keith DCell Biochem. Biophys. 60:3-11inferred by electronic annotationIEAGOIEA

BAP1:Ub-HCFC1 deubiquitinates BAP1:Ub-HCFC1

Reactome DB_ID: 9790703

Reactome DB_ID: 113518

water [ChEBI:15377]

water

ChEBI15377

Reactome DB_ID: 9790705

BAP1:HCFC1 [nucleoplasm]

BAP1:HCFC1

Reactome DB_ID: 9789992

EQUAL

729

EQUAL

Reactome DB_ID: 9761007

EQUAL

2035

EQUAL

Reactome Database ID Release 759790705Database 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=9790705ReactomeR-MMU-5690817

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=R-MMU-5690817.1Converted from EntitySet in Reactome

Reactome DB_ID: 9790707

K48-polyUb, K63-polyUb [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9790703

GO0004843

GO molecular function

Reactome Database ID Release 759790708Database 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=9790708Reactome Database ID Release 759790710Database 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=9790710ReactomeR-MMU-5690759

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=R-MMU-5690759.1BRCA1 associated protein 1 (BAP1) is a tumour suppressor that is believed to mediate its effects through chromatin modulation, transcriptional regulation, and possibly via the ubiquitin-proteasome system and the DNA damage response pathway (Murali et al. 2013). BAP1 mediates the deubiquitination of Host cell factor 1 (HCFC1) thereby regulating cell growth (Eletr & Wilinson 2011), though deubiquitination of HCFC1 does not lead to increased HCFC1 stability. HCFC1 is K48 and K63 ubiquitinated; the major site of linkage are lysines 1807 and 1808 (Machida et al. 2009).

inferred by electronic annotationIEAGOIEA

Histone H2A is dubiquitinated by the PR-DUB complex

Reactome DB_ID: 113518

Converted from EntitySet in Reactome

Reactome DB_ID: 9790463

Ub-histone H2A [nucleoplasm]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: 9776905

Histone H2A [nucleoplasm]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: 9707835

Ub [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUbiquitin (Ubc 3) [nucleoplasm]Ubiquitin (Ubb 2) [nucleoplasm]Ubiquitin (Uba52) [nucleoplasm]Ubb [nucleoplasm]Ubiquitin (Ubc 2) [nucleoplasm]Ubiquitin (Ubb 4) [nucleoplasm]Ubiquitin (Pps27a) [nucleoplasm]Ubiquitin (Ubb 3) [nucleoplasm]Ubiquitin (Ubc 1) [nucleoplasm]Ubiquitin (Ubb 1) [nucleoplasm]

UniProtP0CG50UniProtP0CG49UniProtP62984UniProtP62983PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9790726

PR-DUB complex [nucleoplasm]

PR-DUB complex

Reactome DB_ID: 9761007

EQUAL

2035

EQUAL

Reactome DB_ID: 9790714

PR-DUB core complex [nucleoplasm]

PR-DUB core complex

Converted from EntitySet in Reactome

Reactome DB_ID: 9790002

Reactome DB_ID: 9789992

EQUAL

729

EQUAL

Reactome Database ID Release 759790714Database 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=9790714ReactomeR-MMU-5690793

Reactome DB_ID: 9790012

Reactome DB_ID: 9774864

UniProt:Q8CIG3Kdm1b

UniProtQ8CIG3

EQUAL

822

EQUAL

Converted from EntitySet in Reactome

Reactome DB_ID: 9790724

MBD5,MBD6 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMbd5 [nucleoplasm]Mbd6 [nucleoplasm]

UniProtB1AYB6UniProtQ3TY92Reactome Database ID Release 759790726Database 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=9790726ReactomeR-MMU-5690807

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=R-MMU-5690807.1Reactome Database ID Release 759790727Database 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=9790727Reactome Database ID Release 759790729Database 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=9790729ReactomeR-MMU-5690790

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=R-MMU-5690790.1BAP1 is the catalytic component of the PR-DUB complex, which deubiquitinates Lysine-120 monoubiquitinated Histone H2A (H2AK119ub1) (Scheuermann et al. 2010). The PR-DUB complex consists of BAP1, ASXL1/2, KDM1B, FOXK1/2, HCFC1 and MBD5/6 (Yu et al. 2010, Dey et al. 2012, Baymaz et al. 2014).

20436459Pubmed2010Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUBScheuermann, Johanna Cde Ayala Alonso, Andrés GaytánOktaba, KatarzynaLy-Hartig, NgaMcGinty, Robert KFraterman, SvenWilm, MatthiasMuir, Tom WMüller, JürgNature 465:243-722878500Pubmed2012Loss of the tumor suppressor BAP1 causes myeloid transformationDey, AnweshaSeshasayee, DhayaNoubade, RajkumarFrench, Dorothy MLiu, JinfengChaurushiya, Mira SKirkpatrick, Donald SPham, Victoria CLill, Jennie RBakalarski, Corey EWu, JianshengPhu, LilianKatavolos, PaulaLaFave, Lindsay MAbdel-Wahab, OmarModrusan, ZoraSeshagiri, SomasekarDong, KenLin, ZhonghuaBalazs, MercedeszSuriben, RowenaNewton, KimHymowitz, SarahGarcia-Manero, GuillermoMartin, FlaviusLevine, Ross LDixit, Vishva MScience 337:1541-624634419Pubmed2014MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domainBaymaz, H IremFournier, AlexandraLaget, SophieJi, ZonglingJansen, Pascal W T CSmits, Arne HFerry, LaureMensinga, AnneloesPoser, InaSharrocks, AndrewDefossez, Pierre-AntoineVermeulen, MichielProteomics 14:2179-89inferred by electronic annotationIEAGOIEA

UCHL1, UCHL3 cleave ubiquitin adducts

Reactome DB_ID: 9790651

UCHL1,UCHL3:Ub-Lys [cytosol]

UCHL1,UCHL3:Ub-Lys

Converted from EntitySet in Reactome

Reactome DB_ID: 9790605

UCHL1,UCHL3 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUchl1 [cytosol]Uchl3 [cytosol]

UniProtQ9R0P9UniProtQ9JKB1Converted from EntitySet in Reactome

Reactome DB_ID: 9790649

Ub-Lys [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUbb [cytosol]Ubc [cytosol]Rps27a [cytosol]Uba52 [cytosol]

Reactome Database ID Release 759790651Database 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=9790651ReactomeR-MMU-6782633

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=R-MMU-6782633.1

Reactome DB_ID: 29356

Reactome DB_ID: 9790653

UCHL1,UCHL3:Ub [cytosol]

UCHL1,UCHL3:Ub

Converted from EntitySet in Reactome

Reactome DB_ID: 9790605

Converted from EntitySet in Reactome

Reactome DB_ID: 9707516

Ub [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUbiquitin (Pps27a) [cytosol]Ubiquitin (Uba52) [cytosol]Ubiquitin (Ubb 2) [cytosol]Ubiquitin (Ubc 2) [cytosol]Ubb [cytosol]Ubiquitin (Ubb 3) [cytosol]Ubiquitin (Ubc 3) [cytosol]Ubiquitin (Ubb 1) [cytosol]Ubiquitin (Ubb 4) [cytosol]Ubiquitin (Ubc 1) [cytosol]

Reactome Database ID Release 759790653Database 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=9790653ReactomeR-MMU-6782592

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=R-MMU-6782592.1

Reactome DB_ID: 1131871

cytoplasmGO0005737

L-lysinium(1+) [ChEBI:32551]

L-lysinium(1+)

L-lysine monocationInChI=1S/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)/p+1/t5-/m0/s1C6H15N2O2L-lysine[NH3+]CCCC[C@H]([NH3+])C([O-])=OL-lysiniumKDXKERNSBIXSRK-YFKPBYRVSA-O147.19558(2S)-2,6-diammoniohexanoate

ChEBI32551PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9790651

Reactome Database ID Release 759790654Database 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=9790654Reactome Database ID Release 759790656Database 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=9790656ReactomeR-MMU-5690319

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=R-MMU-5690319.1UCHL1 and UCHL3 can hydrolyze several short C-terminal ubiquitin adducts to generate ubiquitin monomers (Wilkinson et al. 1989, Wada et al. 1998, Larsen et al. 1998). This liberates small molecule nucleophiles that may have inadvertently reacted with Ub C-terminal thiolesters. Because these enzymes can cleave small peptides from the C-terminus of Ub, they could also function in recycling Ub from incomplete proteasomal or lysosomal protein degradation. UCHL3, but not UCHL1, is able to cleave the C-terminus of Neural precursor cell expressed developmentally downregulated protein 8 (NEDD8), a ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin-RING ligases (Wada et al. 1998, Enchev et al. 2015). UCHL1 and 3 are specifically expressed in neurons, cells of the diffuse neuroendocrine system and their tumors. A polymorphism (S18Y) in UCHL1 is associated with a reduced risk for Parkinson's disease (Wang et al. 2002) and its overexpression is protective in models of Alzheimer's disease (Gong et al. 2006). UCHL1 has been shown to interact with alpha-synuclein, but as a ubiquitin ligase rather than as a ubiquitin hydrolase (Liu et al. 2002). It is K63-polyubiquitinated by Parkin in cooperation with the Ubc13/Uev1a E2 ubiquitin-conjugating enzyme complex, promoting UCH-L1 degradation by the autophagy-lysosome pathway (McKeon et al. 2015).

9521656Pubmed1998Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolasesLarsen, C NKrantz, B AWilkinson, K DBiochemistry 37:3358-6812408865Pubmed2002The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibilityLiu, YichinFallon, LaraLashuel, Hilal ALiu, ZhihuaLansbury, Peter TCell 111:209-1825403879Pubmed2015Parkin-mediated K63-polyubiquitination targets ubiquitin C-terminal hydrolase L1 for degradation by the autophagy-lysosome systemMcKeon, Jeanne ESha, DiLi, LianChin, Lih-ShenCell. Mol. Life Sci. 72:1811-2425531226Pubmed2015Protein neddylation: beyond cullin-RING ligasesEnchev, Radoslav ISchulman, Brenda APeter, MatthiasNat. Rev. Mol. Cell Biol. 16:30-449790970Pubmed1998Cleavage of the C-terminus of NEDD8 by UCH-L3Wada, HKito, KCaskey, L SYeh, E TKamitani, TBiochem. Biophys. Res. Commun. 251:688-922530630Pubmed1989The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolaseWilkinson, K DLee, K MDeshpande, SDuerksen-Hughes, PBoss, J MPohl, JScience 246:670-316923396Pubmed2006Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memoryGong, BingCao, ZixuanZheng, PingVitolo, Ottavio VLiu, ShuminStaniszewski, AgnieszkaMoolman, DonnaZhang, HongShelanski, MichaelArancio, OttavioCell 126:775-8812210873Pubmed2002ACT and UCH-L1 polymorphisms in Parkinson's disease and age of onsetWang, JianZhao, Chun-YingSi, Yan-MeiLiu, Zhuo-LinChen, BiaoYu, LongMov. Disord. 17:767-71inferred by electronic annotationIEAGOIEA

UCHL3, SENP8 cleave NEDD8

Reactome DB_ID: 9790733

UCHL3,SENP8:NEDD8(1-88) [cytosol]

UCHL3,SENP8:NEDD8(1-88)

Reactome DB_ID: 9790731

UniProt:P29595Nedd8

UniProtP29595

EQUAL

Reactome DB_ID: 9790603

UniProt:Q9JKB1Uchl3

EQUAL

230

EQUAL

Reactome Database ID Release 759790733Database 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=9790733ReactomeR-MMU-6782635

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=R-MMU-6782635.1

Reactome DB_ID: 29356

Reactome DB_ID: 9790739

EQUAL

Reactome DB_ID: 9790737

UCHL3,SENP8:NEDD8 [cytosol]

UCHL3,SENP8:NEDD8

Reactome DB_ID: 9790735

EQUAL

Reactome DB_ID: 9790603

EQUAL

230

EQUAL

Reactome Database ID Release 759790737Database 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=9790737ReactomeR-MMU-6782643

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=R-MMU-6782643.1PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 9790733

GO0019784

GO molecular function

Reactome Database ID Release 759790740Database 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=9790740Reactome Database ID Release 759790742Database 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=9790742ReactomeR-MMU-5690808

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=R-MMU-5690808.1UCHL3 and SENP8 (DEN1) remove the C-terminal extension of NEDD8 propeptides, exposing a C-terminal Gly residue. UCHL3 can also process ubiquitin (Wada et al. 1998). UCHL3 and SENP8 are probably functionally redundant in NEDD8 processing as deletion of either enzyme does not lead to neddylation defects (Chan et al. 2008, Kurihara et al. 2000).

18782863Pubmed2008DEN1 deneddylates non-cullin proteins in vivoChan, YaruYoon, JeongsookWu, June-TaiKim, Hyung-JunPan, Kuan-TingYim, JeongbinChien, Cheng-TingJ. Cell. Sci. 121:3218-2310713173Pubmed2000Expression and functional analysis of Uch-L3 during mouse developmentKurihara, L JSemenova, ELevorse, J MTilghman, S MMol. Cell. Biol. 20:2498-504inferred by electronic annotationIEAGOIEA

Reactome Database ID Release 759820102Database 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=9820102ReactomeR-MMU-5689603

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=R-MMU-5689603.1DUBs of the Ub C-terminal Hydrolase (UCH) family are thiol proteases that have an N-terminal catalytic domain sometimes followed by C-terminal extensions that mediate protein-protein interactions. Humans have four UCH DUBs (UCH-L1, UCH-L3, UCH37/UCH-L5, and BAP1) that can be divided into the smaller UCH DUBs (UCH-L1 and UCH-L3), which cleave small leaving groups from the C-terminus of ubiquitin (Larsen et al. 1998), and the larger UCH DUBs (UCH37 and BAP1), which can disassemble poly-Ub chains (Misaghi et al. 2009, Lam et al. 1997).

19243136Pubmed2009Polyubiquitin binding and disassembly by deubiquitinating enzymesReyes-Turcu, Francisca EWilkinson, Keith DChem. Rev. 109:1495-50816325574Pubmed2005A genomic and functional inventory of deubiquitinating enzymesNijman, Sebastian M BLuna-Vargas, Mark P AVelds, ArnoBrummelkamp, Thijn RDirac, Annette M GSixma, Titia KBernards, RCell 123:773-86inferred by electronic annotationIEAGOIEA