{PDOC00326} {PS00388; PROTEASOME_ALPHA_1} {PS51475; PROTEASOME_ALPHA_2} {BEGIN} ******************************************************* * Proteasome alpha-type subunit signature and profile * ******************************************************* The proteasome (or macropain) (EC 3.4.25.1) [1 to 6] is a multicatalytic proteinase complex that seems to be involved in an ATP/ubiquitin-dependent nonlysosomal proteolytic pathway. The core of this 2.5 MDa enzyme complex is formed by the 20S proteasome (core particle, CP), a barrel-shaped protease of about 700 KDa that associates with one or two 19S regulatory complexes. The 20S proteasome subunits can be classified, on the basis of sequence similarities, into two related families, alpha and beta (see ). The 20S proteasome is ubiquitous in archaea and in eukaryotes. In bacteria, the 20S has been found only in actinomycetes. The 20S proteasome is composed of four stacked heptameric rings. Narrow substrate entry channels are created by the two outer rings, which are each formed by seven alpha subunits. The two inner rings create an internal chamber that houses the proteolytic active sites responsible for protein cleavage; these rings are each formed by seven beta subunits (see ). 20S proteasome alpha subunits include highly conserved N-terminal extensions that are absent from beta subunits. These N-termini form a gate that controls substrate passage through the central alpha-ring channel. Archaeal and bacterial 20S proteasomes usually have a single type of alpha subunit and beta subunit, each present in 14 copies in each particle. Thus, these proteasomes have 14 active sites arrayed within their central chambers. In eukaryotes, seven distinct alpha-subunit paralogs form each heptameric outer ring and seven distinct beta-subunit paralogs form each inner ring. Only three of the seven eukaryotic beta subunits (beta1, beta2 and beta5) retain an intact active site, so each eukaryotic 20S proteasome has six proteolytic active sites [7]. Subunits that belong to the alpha-type group are proteins of from 210 to 290 amino acids that share a number of conserved sequence regions. The core of the alpha subunit is a sandwich of two five-stranded antiparallel beta-sheets. The beta sandwich is flanked by the alpha helices H3, H4, and H5 on top and by H1 and H2 at the bottom (see ) [8]. Some subunits that are known to belong to this family are listed below: - Vertebrate subunits C2 (nu), C3, C8, C9, iota and zeta. - Drosophila PROS-25, PROS-28.1, PROS-29 and PROS-35. - Yeast C1 (PRS1), C5 (PRS3), C7-alpha (Y8) (PRS2), Y7, Y13, PRE5, PRE6 and PUP2. - Arabidopsis thaliana subunits alpha and PSM30. - Thermoplasma acidophilum alpha-subunit. In this archaebacteria the proteasome is composed of only two different subunits. - Rhodococcus erythropolis 20S proteasome alpha subunit 1 (PrcA 1) and 2 (PrcA 2). As a signature pattern for proteasome A-type subunits we selected the best conserved region, which is located in the N-terminal part of these proteins. We also have developed a profile which covers the whole conserved region. -Consensus pattern: [FYNAGS]-x(4)-[STNLV]-x-[FYW]-S-[PDS]-x(0,1)-G-[RKHDS]- x(2)-Q-[LIVA]-[DENR]-[YH]-[GSAD]-x(2)-[GSAG] -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: These proteins belong to family T1 in the classification of peptidases [9,E2]. -Last update: May 2020 / Text revised. [ 1] Rivett A.J. "Proteasomes: multicatalytic proteinase complexes." Biochem. J. 291:1-10(1993). PubMed=7682410; DOI=10.1042/bj2910001 [ 2] Rivett A.J. "The multicatalytic proteinase of mammalian cells." Arch. Biochem. Biophys. 268:1-8(1989). PubMed=2643381; DOI=10.1016/0003-9861(89)90558-4 [ 3] Goldberg A.L., Rock K.L. "Proteolysis, proteasomes and antigen presentation." Nature 357:375-379(1992). PubMed=1317508; DOI=10.1038/357375a0 [ 4] Wilk S. "Proteasomes. Multicatalytic proteinase complexes." Enzyme. Protein. 47:187-188(1993). PubMed=7697118 [ 5] Hilt W., Wolf D.H. "Proteasomes: destruction as a programme." Trends Biochem. Sci. 21:96-102(1996). PubMed=8882582 [ 6] Kwon Y.D., Nagy I., Adams P.D., Baumeister W., Jap B.K. "Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly." J. Mol. Biol. 335:233-245(2004). PubMed=14659753; DOI=10.1016/j.jmb.2003.08.029 [ 7] Budenholzer L., Cheng C.L., Li Y., Hochstrasser M. "Proteasome Structure and Assembly." J. Mol. Biol. 429:3500-3524(2017). PubMed=28583440; DOI=10.1016/j.jmb.2017.05.027 [ 8] Loewe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. "Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution." Science 268:533-539(1995). PubMed=7725097; DOI=10.1126/science.7725097 [ 9] Rawlings N.D., Barrett A.J. "Families of serine peptidases." Methods. Enzymol. 244:19-61(1994). PubMed=7845208; DOI=10.1016/0076-6879(94)44004-2 [E2] https://www.uniprot.org/docs/peptidas -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}