Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT68GPI)

• DTT Name: Proteasome beta-5 (PS beta-5)
• Synonyms: Proteasome subunit beta type-5; Proteasome subunit X; Proteasome subunit MB1; Proteasome epsilon chain; Proteasome chain 6; Multicatalytic endopeptidase complex epsilon chain; Macropain epsilon chain; MB1; LMPX
• Gene Name: PSMB5
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Peptidase
• UniProt ID: PSB5_HUMAN
• TTD ID: T49031
• EC Number: EC 3.4.25.1
• Sequence:
  MALASVLERPLPVNQRGFFGLGGRADLLDLGPGSLSDGLSLAAPGWGVPEEPGIEMLHGT
  TTLAFKFRHGVIVAADSRATAGAYIASQTVKKVIEINPYLLGTMAGGAADCSFWERLLAR
  QCRIYELRNKERISVAAASKLLANMVYQYKGMGLSMGTMICGWDKRGPGLYYVDSEGNRI
  SGATFSVGSGSVYAYGVMDRGYSYDLEVEQAYDLARRAIYQATYRDAYSGGAVNLYHVRE
  DGWIRVSSDNVADLHEKYSGSTP
• Function: 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.
• KEGG Pathway:
  Proteasome (hsa03050)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  ER-Phagosome pathway (R-HSA-1236974)
  Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978)
  Autodegradation of Cdh1 by Cdh1 (R-HSA-174084)
  SCF-beta-TrCP mediated degradation of Emi1 (R-HSA-174113)
  APC/C (R-HSA-174154)
  APC/C (R-HSA-174178)
  Cdc20 (R-HSA-174184)
  Vpu mediated degradation of CD4 (R-HSA-180534)
  Vif-mediated degradation of APOBEC3G (R-HSA-180585)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)
  Downstream TCR signaling (R-HSA-202424)
  Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733)
  Separation of Sister Chromatids (R-HSA-2467813)
  FCERI mediated NF-kB activation (R-HSA-2871837)
  Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425)
  Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)
  ABC-family proteins mediated transport (R-HSA-382556)
  AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408)
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  Degradation of AXIN (R-HSA-4641257)
  Degradation of DVL (R-HSA-4641258)
  Hedgehog ligand biogenesis (R-HSA-5358346)
  Hh mutants are degraded by ERAD (R-HSA-5362768)
  Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  Degradation of GLI1 by the proteasome (R-HSA-5610780)
  Degradation of GLI2 by the proteasome (R-HSA-5610783)
  GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785)
  Hedgehog 'on' state (R-HSA-5632684)
  Regulation of RAS by GAPs (R-HSA-5658442)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)
  NIK-->noncanonical NF-kB signaling (R-HSA-5676590)
  Defective CFTR causes cystic fibrosis (R-HSA-5678895)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  UCH proteinases (R-HSA-5689603)
  Ub-specific processing proteases (R-HSA-5689880)
  Assembly of the pre-replicative complex (R-HSA-68867)
  Orc1 removal from chromatin (R-HSA-68949)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  G2/M Checkpoints (R-HSA-69481)
  Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601)
  Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  Neddylation (R-HSA-8951664)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Interleukin-1 signaling (R-HSA-9020702)
  Negative regulation of NOTCH4 signaling (R-HSA-9604323)
  KEAP1-NFE2L2 pathway (R-HSA-9755511)
  GSK3B and BTRC (R-HSA-9762114)
  Antigen processing (R-HSA-983168)
  Activation of NF-kappaB in B cells (R-HSA-1169091)

Molecular Interaction Atlas (MIA) of This DTT

26 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Peptide analog 11	DML9C64	N. A.	N. A.	Patented	[1]
Peptide analog 13	DMWI6V3	N. A.	N. A.	Patented	[1]
Peptide analog 17	DMJ91EM	N. A.	N. A.	Patented	[1]
Peptide analog 19	DMLIVT6	N. A.	N. A.	Patented	[1]
Peptide analog 21	DMJDFS1	N. A.	N. A.	Patented	[1]
Peptide analog 23	DMDU21R	N. A.	N. A.	Patented	[1]
Peptide analog 25	DMFBQHZ	N. A.	N. A.	Patented	[1]
Peptide analog 27	DML4XJ2	N. A.	N. A.	Patented	[1]
Peptide analog 28	DMHT4PF	N. A.	N. A.	Patented	[1]
Peptide analog 31	DMS9O6I	N. A.	N. A.	Patented	[1]
Peptide analog 33	DML5P6O	N. A.	N. A.	Patented	[1]
Peptide analog 34	DMG4EOP	N. A.	N. A.	Patented	[1]
Peptide analog 36	DMB4LNI	N. A.	N. A.	Patented	[1]
Peptide analog 37	DMVX71N	N. A.	N. A.	Patented	[1]
Peptide analog 38	DM9FL81	N. A.	N. A.	Patented	[1]
Peptide analog 39	DMYJOTP	N. A.	N. A.	Patented	[1]
Peptide analog 41	DM96KXE	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-43	DMQUE6D	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-44	DMRTQ4I	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-46	DMP3MXK	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-48	DMVQTR2	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-49	DMK0GTV	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-51	DM0LXT2	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-53	DM6JV1W	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-55	DMY52ZB	N. A.	N. A.	Patented	[1]
PMID29865878-Compound-8	DMX1E6O	N. A.	N. A.	Patented	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID24946214C3b	DMNPA2C	Discovery agent	N.A.	Investigative	[2]

References

• [1] A patent review of immunoproteasome inhibitors.Expert Opin Ther Pat. 2018 Jul;28(7):517-540.
• [2] Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors. Eur J Med Chem. 2014 Aug 18;83:1-14.