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proteasome 20S subunit beta 8

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2408

Nomenclature: proteasome 20S subunit beta 8

Family: T1: Proteasome

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 276 6p21.32 PSMB8 proteasome 20S subunit beta 8
Mouse - 276 17 17.98 cM Psmb8 proteasome (prosome, macropain) subunit, beta type 8 (large multifunctional peptidase 7)
Rat - 276 20p12 Psmb8 proteasome 20S subunit beta 8
Previous and Unofficial Names Click here for help
large multifunctional protease 7 | Lmp7 | low molecular mass protein 7 | macropain subunit C13 | multicatalytic endopeptidase complex subunit C13 | proteasome component C13 | proteasome subunit beta-5i | proteasome subunit MC13 | Ring10 | proteasome (prosome, macropain) subunit, beta type, 8 | proteasome (prosome | proteasome subunit beta 8
Database Links Click here for help
Specialist databases
MEROPS T01.015 (Hs)
Other databases
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.25.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
HT1042 Small molecule or natural product Primary target of this compound Hs Inhibition 6.4 pKi 4
pKi 6.4 (Ki 4.2x10-7 M) [4]
KZR-616 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.4 pIC50 6
pIC50 7.4 (IC50 3.9x10-8 M) [6]
Description: Inhibition of proteolytic activity measured in MOLT-4 (human T cell leukemia) cells using the ProCISE ELISA.
KZR-616 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Inhibition 7.2 pIC50 6
pIC50 7.2 (IC50 5.7x10-8 M) [6]
Description: Inhibition of proteolytic activity measured in A20 (mouse B-cell lymphoma) cell lysate using the ProCISE ELISA.
ONX-0914 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 7.0 pIC50 8
pIC50 7.0 (IC50 1x10-7 M) [8]
View species-specific inhibitor tables
Immunopharmacology Comments
PSMB8 is a component of the immunoproteasome [5]. It is a IFN-γ-inducible gene [1], expressed by immune and non-immune cell types [7]. Genetic mutations in PSMB8 [2-3] have been identified in patients with the autoinflammatory disorder, CANDLE syndrome [9].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0060337 type I interferon signaling pathway TAS
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 2 GO processes
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent TAS
click arrow to show/hide IEA associations
GO:0019882 antigen processing and presentation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0000209 protein polyubiquitination TAS
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0050852 T cell receptor signaling pathway TAS
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS
GO:0060337 type I interferon signaling pathway TAS
GO:0070498 interleukin-1-mediated signaling pathway TAS
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  CANDLE syndrome
Synonyms: Autoinflammation, lipodystrophy, and dermatosis syndrome [OMIM: 256040]
Chronic atypical neutrophilic dermatosis-lipodystrophy-elevated temperature syndrome [Orphanet: ORPHA325004]
OMIM: 256040
Orphanet: ORPHA325004
Disease:  JMP syndrome
Synonyms: Autoinflammation, lipodystrophy, and dermatosis syndrome [OMIM: 256040]
Joint contractures-muscular atrophy-microcytic anemia-panniculitis-associated lipodystrophy syndrome [Orphanet: ORPHA324999]
OMIM: 256040
Orphanet: ORPHA324999
Disease:  Nakajo-Nishimura syndrome
Synonyms: Amyotrophy - fat tissue anomaly [Orphanet: ORPHA2615]
Autoinflammation, lipodystrophy, and dermatosis syndrome [OMIM: 256040]
Secondary hypertrophic osteoperiostosis with pernio [Orphanet: ORPHA2615]
OMIM: 256040
Orphanet: ORPHA2615

References

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1. Basler M, Kirk CJ, Groettrup M. (2013) The immunoproteasome in antigen processing and other immunological functions. Curr Opin Immunol, 25 (1): 74-80. [PMID:23219269]

2. Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, Montealegre G, Biancotto A, Reinhardt A, Almeida de Jesus A et al.. (2015) Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest, 125 (11): 4196-211. [PMID:26524591]

3. Cavalcante MP, Brunelli JB, Miranda CC, Novak GV, Malle L, Aikawa NE, Jesus AA, Silva CA. (2016) CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature-a rare case with a novel mutation. Eur J Pediatr, 175 (5): 735-40. [PMID:26567544]

4. Fan H, Angelo NG, Warren JD, Nathan CF, Lin G. (2014) Oxathiazolones Selectively Inhibit the Human Immunoproteasome over the Constitutive Proteasome. ACS Med Chem Lett, 5 (4): 405-10. [PMID:24900849]

5. Ferrington DA, Gregerson DS. (2012) Immunoproteasomes: structure, function, and antigen presentation. Prog Mol Biol Transl Sci, 109: 75-112. [PMID:22727420]

6. Johnson HWB, Lowe E, Anderl JL, Fan A, Muchamuel T, Bowers S, Moebius DC, Kirk C, McMinn DL. (2018) Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem, 61 (24): 11127-11143. [PMID:30380863]

7. Keller IE, Vosyka O, Takenaka S, Kloß A, Dahlmann B, Willems LI, Verdoes M, Overkleeft HS, Marcos E, Adnot S et al.. (2015) Regulation of immunoproteasome function in the lung. Sci Rep, 5: 10230. [PMID:25989070]

8. Muchamuel T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J et al.. (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med, 15 (7): 781-7. [PMID:19525961]

9. Torrelo A, Colmenero I, Requena L, Paller AS, Ramot Y, Richard Lee CC, Vera A, Zlotogorski A, Goldbach-Mansky R, Kutzner H. (2015) Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome. Am J Dermatopathol, 37 (7): 517-22. [PMID:26091509]

How to cite this page

T1: Proteasome: proteasome 20S subunit beta 8. Last modified on 12/09/2019. Accessed on 20/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2408.