proteasome 20S subunit beta 8 | T1: Proteasome | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

proteasome 20S subunit beta 8

target has curated data in GtoImmuPdb

Target id: 2408

Nomenclature: proteasome 20S subunit beta 8

Family: T1: Proteasome

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 276 6p21.3 PSMB8 proteasome 20S subunit beta 8
Mouse - 276 17 B1 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
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
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
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.25.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
HT1042 Hs Inhibition 6.4 pKi 4
pKi 6.4 (Ki 4.2x10-7 M) [4]
KZR-616 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 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 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 4 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
GO:1902036 regulation of hematopoietic stem cell differentiation TAS
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:1902036 regulation of hematopoietic stem cell differentiation TAS
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
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

Show »

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 Medicinal Chemistry Letters, 5 (4): 405-410.

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 17/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2408.