Proteasome subunit alpha type-1

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).

Classification

Family (Pfam)

PF00227 Proteasome, PF10584 Proteasome_A_N

InterPro

Ntn_hydrolases_N, Proteasome_alpha, Proteasome_alpha-type, Proteasome_alpha1, Proteasome_asu_N, Proteasome_sua/b

Functional cluster

Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 126

• 4R3O X-ray 2.60A
• 4R67 X-ray 2.89A
• 5A0Q EM 3.50A
• 5GJQ EM 4.50A
• 5GJR EM 3.50A
• 5L4G EM 4.02A
• 5LE5 X-ray 1.80A
• 5LEX X-ray 2.20A
• 5LEY X-ray 1.90A
• 5LEZ X-ray 2.19A
• 5LF0 X-ray 2.41A
• 5LF1 X-ray 2.00A
• … and 114 more

A predicted model is available from AlphaFold.

Gene Ontology · 37

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0016604 nuclear body
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0000502 proteasome complex
• GO:0005839 proteasome core complex
• GO:0019773 proteasome core complex, alpha-subunit complex
• GO:0034515 proteasome storage granule
• GO:0008021 synaptic vesicle
• GO:0001530 lipopolysaccharide binding
• GO:0006915 apoptotic process
• GO:0043374 CD8-positive, alpha-beta T cell differentiation
• GO:0160165 CD8-positive, alpha-beta T cell homeostasis
• GO:0071357 cellular response to type I interferon
• GO:0006974 DNA damage response
• GO:0006281 DNA repair
• GO:0030317 flagellated sperm motility
• GO:0002376 immune system process
• GO:0051321 meiotic cell cycle
• GO:0002862 negative regulation of inflammatory response to antigenic stimulus
• GO:0045590 negative regulation of regulatory T cell differentiation
• GO:0032743 positive regulation of interleukin-2 production
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:0032729 positive regulation of type II interferon production
• GO:0010498 proteasomal protein catabolic process
• GO:0010499 proteasomal ubiquitin-independent protein catabolic process
• GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
• GO:2000045 regulation of G1/S transition of mitotic cell cycle
• GO:0061136 regulation of proteasomal protein catabolic process
• GO:0006979 response to oxidative stress
• GO:0034341 response to type II interferon
• GO:0007283 spermatogenesis
• GO:0045063 T-helper 1 cell differentiation
• GO:0072539 T-helper 17 cell differentiation
• GO:0045061 thymic T cell selection

Drugs targeting this protein · 7

• OPROZOMIB inhibitor
• IXAZOMIB inhibitor
• BORTEZOMIB inhibitor
• IXAZOMIB CITRATE inhibitor
• MARIZOMIB inhibitor
• CARFILZOMIB inhibitor
• BORTEZOMIB D-MANNITOL inhibitor

Related proteins · sequence + function similarity

• Proteasome subunit alpha type-1 1.00
• Proteasome subunit alpha type-1 1.00
• Proteasome subunit alpha type-1 1.00
• Proteasome subunit alpha type-1 0.99
• Proteasome subunit alpha type-1 0.99
• Proteasome subunit alpha type-1 0.98
• Proteasome subunit alpha type-1 0.91
• Proteasome subunit alpha type-1 0.90
• Proteasome subunit alpha type-1-B 0.90
• Proteasome subunit alpha type-1 0.89
• Probable proteasome subunit alpha type-6 0.89
• Proteasome subunit alpha type-1-A 0.88

Co-cited proteins · studied together in the literature

• Proteasome subunit beta type-5 13 shared papers
• Neurogenic locus notch homolog protein 3 1 shared papers
• Proteasome subunit alpha type-6 13 shared papers
• Proteasome subunit alpha type-5 12 shared papers
• Proteasome subunit alpha type-4 13 shared papers
• Proteasome subunit alpha type-2 13 shared papers
• Proteasome subunit beta type-6 12 shared papers
• Proteasome subunit beta type-1 12 shared papers
• Proteasome subunit alpha type-3 13 shared papers
• Proteasome subunit beta type-3 12 shared papers
• Proteasome subunit beta type-2 12 shared papers
• Proteasome subunit beta type-7 11 shared papers

Literature · 27 cited papers

• AKIRIN2 controls the nuclear import of proteasomes in vertebrates. Nature · 2021
• ZFAND1 recruits p97 and the 26S proteasome to promote the clearance of arsenite-induced stress granules. Mol. Cell · 2018
• The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design. Science · 2016
• An atomic structure of the human 26S proteasome. Nat. Struct. Mol. Biol. · 2016
• Structure of the human 26S proteasome at a resolution of 3.9 Aa. Proc. Natl. Acad. Sci. U.S.A. · 2016
• Human 20S proteasome activity towards fluorogenic peptides of various chain lengths. Biol. Chem. · 2016
• Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core. Nat. Commun. · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Crystal structure of the human 20S proteasome in complex with carfilzomib. Structure · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Molecular architecture and assembly of the eukaryotic proteasome. Annu. Rev. Biochem. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• … and 15 more in the literature graph