Proteasome subunit beta

Details

Name
Proteasome subunit beta
Synonyms
  • 20S proteasome beta subunit
  • 3.4.25.1
  • Proteasome core protein PrcB
Gene Name
prcB
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051259|Proteasome subunit beta
MTWPLPDRLSINSLSGTPAVDLSSFTDFLRRQAPELLPASISGGAPLAGGDAQLPHGTTI
VALKYPGGVVMAGDRRSTQGNMISGRDVRKVYITDDYTATGIAGTAAVAVEFARLYAVEL
EHYEKLEGVPLTFAGKINRLAIMVRGNLAAAMQGLLALPLLAGYDIHASDPQSAGRIVSF
DAAGGWNIEEEGYQAVGSGSLFAKSSMKKLYSQVTDGDSGLRVAVEALYDAADDDSATGG
PDLVRGIFPTAVIIDADGAVDVPESRIAELARAIIESRSGADTFGSDGGEK
Number of residues
291
Molecular Weight
30304.72
Theoretical pI
Not Available
GO Classification
Functions
threonine-type endopeptidase activity / zymogen binding
Processes
growth / modification-dependent protein catabolic process / pathogenesis / proteasomal protein catabolic process / proteolysis involved in cellular protein catabolic process
Components
cytoplasm / extracellular region / plasma membrane / proteasome core complex, beta-subunit complex
General Function
Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues (PubMed:16468985). In complex with the ATPase Mpa, degrades protein targets conjugated to a prokaryotic ubiquitin-like protein (Pup). Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins (PubMed:17082771). One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice (PubMed:18059281). Likely functions to recycle amino acids under nutrient starvation, thereby enabling the cell to maintain basal metabolic activities (PubMed:20711362) (By similarity). The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated. A proteolysis-independent activity of the proteasome core is required for optimal growth of M.tuberculosis in mouse lungs and for RNI resistance; in contrast, long-term survival of M.tuberculosis in stationary phase and during starvation in vitro and in the chronic phase of mouse infection required a proteolytically active proteasome (PubMed:20711362).
Specific Function
Threonine-type endopeptidase activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051260|Proteasome subunit beta (prcB)
GTGACCTGGCCGTTGCCCGATCGCCTGTCCATTAATTCACTCTCTGGAACACCCGCTGTA
GACCTATCTTCTTTCACTGACTTCCTGCGCCGCCAGGCGCCGGAGTTGCTGCCGGCAAGC
ATCAGCGGCGGTGCGCCACTCGCAGGCGGCGATGCGCAACTGCCGCACGGCACCACCATT
GTCGCGCTGAAATACCCCGGCGGTGTTGTCATGGCGGGTGACCGGCGTTCGACGCAGGGC
AACATGATTTCTGGGCGTGATGTGCGCAAGGTGTATATCACCGATGACTACACCGCTACC
GGCATCGCTGGCACGGCTGCGGTCGCGGTTGAGTTTGCCCGGCTGTATGCCGTGGAACTT
GAGCACTACGAGAAGCTCGAGGGTGTGCCGCTGACGTTTGCCGGCAAAATCAACCGGCTG
GCGATTATGGTGCGTGGCAATCTGGCGGCCGCGATGCAGGGTCTGCTGGCGTTGCCGTTG
CTGGCGGGCTACGACATTCATGCGTCTGACCCGCAGAGCGCGGGTCGTATCGTTTCGTTC
GACGCCGCCGGCGGTTGGAACATCGAGGAAGAGGGCTATCAGGCGGTGGGCTCGGGTTCG
CTGTTCGCGAAGTCGTCGATGAAGAAGTTGTATTCGCAGGTTACCGACGGTGATTCGGGG
CTGCGGGTGGCGGTCGAGGCGCTCTACGACGCCGCCGACGACGACTCCGCCACCGGCGGT
CCGGACCTGGTGCGGGGCATCTTTCCGACGGCGGTGATCATCGACGCCGACGGGGCGGTT
GACGTGCCGGAGAGCCGGATTGCCGAATTGGCCCGCGCGATCATCGAAAGCCGTTCGGGT
GCGGATACTTTCGGCTCCGATGGCGGTGAGAAGTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WHT9
UniProtKB Entry NamePSB_MYCTU
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [Article]
  2. Lin G, Hu G, Tsu C, Kunes YZ, Li H, Dick L, Parsons T, Li P, Chen Z, Zwickl P, Weich N, Nathan C: Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity. Mol Microbiol. 2006 Mar;59(5):1405-16. [Article]
  3. Pearce MJ, Arora P, Festa RA, Butler-Wu SM, Gokhale RS, Darwin KH: Identification of substrates of the Mycobacterium tuberculosis proteasome. EMBO J. 2006 Nov 15;25(22):5423-32. Epub 2006 Nov 2. [Article]
  4. Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S: In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med. 2007 Dec;13(12):1515-20. Epub 2007 Dec 2. [Article]
  5. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [Article]
  6. Poulsen C, Holton S, Geerlof A, Wilmanns M, Song YH: Stoichiometric protein complex formation and over-expression using the prokaryotic native operon structure. FEBS Lett. 2010 Feb 19;584(4):669-74. doi: 10.1016/j.febslet.2009.12.057. Epub 2010 Jan 18. [Article]
  7. Gandotra S, Lebron MB, Ehrt S: The Mycobacterium tuberculosis proteasome active site threonine is essential for persistence yet dispensable for replication and resistance to nitric oxide. PLoS Pathog. 2010 Aug 12;6(8):e1001040. doi: 10.1371/journal.ppat.1001040. [Article]
  8. Anandan T, Han J, Baun H, Nyayapathy S, Brown JT, Dial RL, Moltalvo JA, Kim MS, Yang SH, Ronning DR, Husson RN, Suh J, Kang CM: Phosphorylation regulates mycobacterial proteasome. J Microbiol. 2014 Sep;52(9):743-54. doi: 10.1007/s12275-014-4416-2. Epub 2014 Sep 2. [Article]
  9. Hu G, Lin G, Wang M, Dick L, Xu RM, Nathan C, Li H: Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate. Mol Microbiol. 2006 Mar;59(5):1417-28. [Article]
  10. Lin G, Li D, de Carvalho LP, Deng H, Tao H, Vogt G, Wu K, Schneider J, Chidawanyika T, Warren JD, Li H, Nathan C: Inhibitors selective for mycobacterial versus human proteasomes. Nature. 2009 Oct 1;461(7264):621-6. doi: 10.1038/nature08357. Epub 2009 Sep 16. [Article]
  11. Lin G, Li D, Chidawanyika T, Nathan C, Li H: Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome. Arch Biochem Biophys. 2010 Sep 15;501(2):214-20. doi: 10.1016/j.abb.2010.06.009. Epub 2010 Jun 15. [Article]
  12. Li D, Li H, Wang T, Pan H, Lin G, Li H: Structural basis for the assembly and gate closure mechanisms of the Mycobacterium tuberculosis 20S proteasome. EMBO J. 2010 Jun 16;29(12):2037-47. doi: 10.1038/emboj.2010.95. Epub 2010 May 11. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04732N-(4-MORPHOLINE)CARBONYL-B-(1-NAPHTHYL)-L-ALANINE-L-LEUCINE BORONIC ACIDexperimentalunknownDetails