Molecule Information

General Information of the Molecule (ID: Mol00572)

• Name: Proteasome subunit beta type-5 (PSMB5) ,Homo sapiens
• Synonyms: Macropain epsilon chain; Multicatalytic endopeptidase complex epsilon chain; Proteasome chain 6; Proteasome epsilon chain; Proteasome subunit MB1; Proteasome subunit X; LMPX; MB1; X
• Molecule Type: Protein
• Gene Name: PSMB5
• Gene ID: 5693
• Location: chr14:23016543-23035230[-]
• 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.
• Uniprot ID: PSB5_HUMAN
• Ensembl ID: ENSG00000100804
• HGNC ID: HGNC:9542

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Bortezomib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Multiple myeloma [1]

• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Resistant Drug: Bortezomib
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/RAS signaling pathway; Regulation; hsa04151
• In Vitro Model: Bone marrow; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
• Experiment for Drug Resistance: Longitudinal copy number aberration (CNA) analysis
• Mechanism Description: Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.

Investigative Drug(s) 1 drug(s) in total

Cortiosteroids

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Multiple myeloma [1]

• Resistant Disease: Multiple myeloma [ICD-11: 2A83.0]
• Resistant Drug: Cortiosteroids
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/RAS signaling pathway; Regulation; hsa04151
• In Vitro Model: Bone marrow; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
• Experiment for Drug Resistance: Longitudinal copy number aberration (CNA) analysis
• Mechanism Description: Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Multiple myeloma [ICD-11: 2A83]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.50E-06; Fold-change: 1.09E+00; Z-score: 4.18E+00
• The Studied Tissue: Peripheral blood
• The Specified Disease: Multiple myeloma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.62E-01; Fold-change: -1.06E-01; Z-score: -1.18E-01

References

• Ref 1: Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016 Sep 29;128(13):1735-44. doi: 10.1182/blood-2016-06-723007. Epub 2016 Aug 11.