PSA_THEAC
ID PSA_THEAC Reviewed; 233 AA.
AC P25156;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 25-MAY-2022, entry version 160.
DE RecName: Full=Proteasome subunit alpha {ECO:0000255|HAMAP-Rule:MF_00289};
DE AltName: Full=20S proteasome alpha subunit {ECO:0000255|HAMAP-Rule:MF_00289};
DE AltName: Full=Proteasome core protein PsmA {ECO:0000255|HAMAP-Rule:MF_00289};
GN Name=psmA {ECO:0000255|HAMAP-Rule:MF_00289}; OrderedLocusNames=Ta1288;
OS Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC
OS 15155 / AMRC-C165).
OC Archaea; Candidatus Thermoplasmatota; Thermoplasmata; Thermoplasmatales;
OC Thermoplasmataceae; Thermoplasma.
OX NCBI_TaxID=273075;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 21-28; 41-54 AND
RP 88-93.
RX PubMed=1991516; DOI=10.1016/0014-5793(91)80120-r;
RA Zwickl P., Lottspeich F., Dahlmann B., Baumeister W.;
RT "Cloning and sequencing of the gene encoding the large (alpha-) subunit of
RT the proteasome from Thermoplasma acidophilum.";
RL FEBS Lett. 278:217-221(1991).
RN [2]
RP SEQUENCE REVISION TO 66-69.
RA Zwickl P.;
RL Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165;
RX PubMed=11029001; DOI=10.1038/35035069;
RA Ruepp A., Graml W., Santos-Martinez M.-L., Koretke K.K., Volker C.,
RA Mewes H.-W., Frishman D., Stocker S., Lupas A.N., Baumeister W.;
RT "The genome sequence of the thermoacidophilic scavenger Thermoplasma
RT acidophilum.";
RL Nature 407:508-513(2000).
RN [4]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY, AND KINETIC
RP PARAMETERS.
RX PubMed=8999862; DOI=10.1074/jbc.272.3.1791;
RA Akopian T.N., Kisselev A.F., Goldberg A.L.;
RT "Processive degradation of proteins and other catalytic properties of the
RT proteasome from Thermoplasma acidophilum.";
RL J. Biol. Chem. 272:1791-1798(1997).
RN [5]
RP SUBUNIT.
RX PubMed=1373380; DOI=10.1002/j.1460-2075.1992.tb05206.x;
RA Puehler G., Weinkauf S., Bachmann L., Mueller S., Engel E., Hegerl R.,
RA Baumeister W.;
RT "Subunit stoichiometry and three-dimensional arrangement in proteasomes
RT from Thermoplasma acidophilum.";
RL EMBO J. 11:1607-1616(1992).
RN [6]
RP CHARACTERIZATION.
RX PubMed=9442034; DOI=10.1074/jbc.273.4.1982;
RA Kisselev A.F., Akopian T.N., Goldberg A.L.;
RT "Range of sizes of peptide products generated during degradation of
RT different proteins by archaeal proteasomes.";
RL J. Biol. Chem. 273:1982-1989(1998).
RN [7]
RP INTERACTION WITH PAN, SUBUNIT, GATED STRUCTURE, AND MUTAGENESIS OF
RP 1-MET--ILE-12.
RX PubMed=16337593; DOI=10.1016/j.molcel.2005.10.019;
RA Smith D.M., Kafri G., Cheng Y., Ng D., Walz T., Goldberg A.L.;
RT "ATP binding to PAN or the 26S ATPases causes association with the 20S
RT proteasome, gate opening, and translocation of unfolded proteins.";
RL Mol. Cell 20:687-698(2005).
RN [8]
RP GATE OPENING MECHANISM, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-66.
RX PubMed=17803938; DOI=10.1016/j.molcel.2007.06.033;
RA Smith D.M., Chang S.C., Park S., Finley D., Cheng Y., Goldberg A.L.;
RT "Docking of the proteasomal ATPases' carboxyl termini in the 20S
RT proteasome's alpha ring opens the gate for substrate entry.";
RL Mol. Cell 27:731-744(2007).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT, AND
RP SUBUNIT.
RX PubMed=7725097; DOI=10.1126/science.7725097;
RA Lowe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R.;
RT "Crystal structure of the 20S proteasome from the archaeon T. acidophilum
RT at 3.4-A resolution.";
RL Science 268:533-539(1995).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT AND
RP T.BRUCEI PA26.
RX PubMed=15916965; DOI=10.1016/j.molcel.2005.04.016;
RA Forster A., Masters E.I., Whitby F.G., Robinson H., Hill C.P.;
RT "The 1.9 A structure of a proteasome-11S activator complex and implications
RT for proteasome-PAN/PA700 interactions.";
RL Mol. Cell 18:589-599(2005).
RN [11]
RP STRUCTURE BY ELECTRON MICROSCOPY (6.8 ANGSTROMS) OF THE OPEN-GATE AND
RP CLOSED-GATE CONFORMATIONS, GATE OPENING MECHANISM, AND MUTAGENESIS OF
RP LEU-81 AND VAL-82.
RX PubMed=18471981; DOI=10.1016/j.molcel.2008.03.004;
RA Rabl J., Smith D.M., Yu Y., Chang S.C., Goldberg A.L., Cheng Y.;
RT "Mechanism of gate opening in the 20S proteasome by the proteasomal
RT ATPases.";
RL Mol. Cell 30:360-368(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEX WITH THE BETA SUBUNIT AND
RP THE C-TERMINUS OF PAN FROM M.JANNASCHII.
RX PubMed=20019667; DOI=10.1038/emboj.2009.382;
RA Yu Y., Smith D.M., Kim H.M., Rodriguez V., Goldberg A.L., Cheng Y.;
RT "Interactions of PAN's C-termini with archaeal 20S proteasome and
RT implications for the eukaryotic proteasome-ATPase interactions.";
RL EMBO J. 29:692-702(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT AND
RP CHIMERIC PA26 CONSTRUCTS.
RX PubMed=19889631; DOI=10.1074/jbc.c109.070425;
RA Stadtmueller B.M., Ferrell K., Whitby F.G., Heroux A., Robinson H.,
RA Myszka D.G., Hill C.P.;
RT "Structural models for interactions between the 20S proteasome and its
RT PAN/19S activators.";
RL J. Biol. Chem. 285:13-17(2010).
RN [14]
RP STRUCTURE BY NMR, AND ACTIVITY REGULATION.
RX PubMed=20360109; DOI=10.1126/science.1184991;
RA Religa T.L., Sprangers R., Kay L.E.;
RT "Dynamic regulation of archaeal proteasome gate opening as studied by TROSY
RT NMR.";
RL Science 328:98-102(2010).
CC -!- FUNCTION: Component of the proteasome core, a large protease complex
CC with broad specificity involved in protein degradation. The
CC T.acidophilum proteasome is able to cleave oligopeptides after Tyr,
CC Leu, Phe, and to a lesser extent after Glu and Arg. Thus, displays
CC chymotrypsin-like activity and low level of caspase-like and trypsin-
CC like activities. {ECO:0000255|HAMAP-Rule:MF_00289,
CC ECO:0000269|PubMed:8999862}.
CC -!- ACTIVITY REGULATION: The formation of the proteasomal ATPase PAN-20S
CC proteasome complex, via the docking of the C-termini of PAN into the
CC intersubunit pockets in the alpha-rings, triggers opening of the gate
CC for substrate entry. Interconversion between the open-gate and close-
CC gate conformations leads to a dynamic regulation of the 20S proteasome
CC proteolysis activity. {ECO:0000255|HAMAP-Rule:MF_00289,
CC ECO:0000269|PubMed:17803938, ECO:0000269|PubMed:20360109}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for Suc-LLVY-Amc (at 55 degrees Celsius)
CC {ECO:0000269|PubMed:8999862};
CC Vmax=28 nmol/min/mg enzyme with Suc-LLVY-Amc as substrate (at 55
CC degrees Celsius) {ECO:0000269|PubMed:8999862};
CC -!- SUBUNIT: The 20S proteasome core is composed of 14 alpha and 14 beta
CC subunits that assemble into four stacked heptameric rings, resulting in
CC a barrel-shaped structure. The two inner rings, each composed of seven
CC catalytic beta subunits, are sandwiched by two outer rings, each
CC composed of seven alpha subunits. The catalytic chamber with the active
CC sites is on the inside of the barrel. Has a gated structure, the ends
CC of the cylinder being occluded by the N-termini of the alpha-subunits.
CC Is capped at one or both ends by the proteasome regulatory ATPase, PAN.
CC {ECO:0000255|HAMAP-Rule:MF_00289, ECO:0000269|PubMed:1373380,
CC ECO:0000269|PubMed:15916965, ECO:0000269|PubMed:16337593,
CC ECO:0000269|PubMed:19889631, ECO:0000269|PubMed:20019667,
CC ECO:0000269|PubMed:7725097}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00289}.
CC -!- PTM: The N-terminus is blocked.
CC -!- MISCELLANEOUS: The configuration of the closed gate contains an opening
CC large enough to allow rapid entry of tetrapeptides but able to impede
CC the entry of proteins and longer peptides.
CC -!- SIMILARITY: Belongs to the peptidase T1A family. {ECO:0000255|HAMAP-
CC Rule:MF_00289}.
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DR EMBL; X59507; CAA42094.1; -; Genomic_DNA.
DR EMBL; AL445067; CAC12411.1; -; Genomic_DNA.
DR PIR; S55350; S55350.
DR RefSeq; WP_010901695.1; NC_002578.1.
DR PDB; 1PMA; X-ray; 3.40 A; A/C/D/E/F/G/H/I/J/K/L/M/N/O=1-233.
DR PDB; 1YA7; X-ray; 2.30 A; A/B/C/D/E/F/G=1-233.
DR PDB; 1YAR; X-ray; 1.90 A; A/B/C/D/E/F/G=1-233.
DR PDB; 1YAU; X-ray; 2.40 A; A/B/C/D/E/F/G=1-233.
DR PDB; 2KU1; NMR; -; A/B/C/D/E/F/G=1-233.
DR PDB; 2KU2; NMR; -; A/B/C/D/E/F/G=1-233.
DR PDB; 3C91; EM; 6.80 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=1-233.
DR PDB; 3C92; EM; 6.80 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=1-233.
DR PDB; 3IPM; X-ray; 4.00 A; A/B/C/D/E/F/G=1-233.
DR PDB; 3J9I; EM; 3.30 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=10-233.
DR PDB; 3JRM; X-ray; 2.90 A; A/B/C/D/E/F/G=7-233.
DR PDB; 3JSE; X-ray; 2.90 A; A/B/C/D/E/F/G=7-233.
DR PDB; 3JTL; X-ray; 3.20 A; A/B/C/D/E/F/G=7-233.
DR PDB; 5VY3; EM; 3.10 A; 0/A/C/E/G/I/K/M/O/Q/S/U/W/Y=10-233.
DR PDB; 5VY4; EM; 3.30 A; 0/A/C/E/G/I/K/M/O/Q/S/U/W/Y=10-233.
DR PDB; 6BDF; EM; 2.80 A; 0/A/C/E/G/I/K/M/O/Q/S/U/W/Y=1-233.
DR PDB; 6UTF; EM; 3.40 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=7-233.
DR PDB; 6UTH; EM; 3.40 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=7-233.
DR PDB; 6UTI; EM; 3.40 A; A/B/C/D/E/F/G/O/P/Q/R/S/T/U=7-233.
DR PDBsum; 1PMA; -.
DR PDBsum; 1YA7; -.
DR PDBsum; 1YAR; -.
DR PDBsum; 1YAU; -.
DR PDBsum; 2KU1; -.
DR PDBsum; 2KU2; -.
DR PDBsum; 3C91; -.
DR PDBsum; 3C92; -.
DR PDBsum; 3IPM; -.
DR PDBsum; 3J9I; -.
DR PDBsum; 3JRM; -.
DR PDBsum; 3JSE; -.
DR PDBsum; 3JTL; -.
DR PDBsum; 5VY3; -.
DR PDBsum; 5VY4; -.
DR PDBsum; 6BDF; -.
DR PDBsum; 6UTF; -.
DR PDBsum; 6UTH; -.
DR PDBsum; 6UTI; -.
DR AlphaFoldDB; P25156; -.
DR BMRB; P25156; -.
DR SMR; P25156; -.
DR STRING; 273075.Ta1288; -.
DR MEROPS; T01.970; -.
DR EnsemblBacteria; CAC12411; CAC12411; CAC12411.
DR GeneID; 1456771; -.
DR KEGG; tac:Ta1288; -.
DR eggNOG; arCOG00971; Archaea.
DR HOGENOM; CLU_035750_4_1_2; -.
DR OMA; FQVEYAR; -.
DR OrthoDB; 57654at2157; -.
DR BRENDA; 3.4.25.1; 6324.
DR EvolutionaryTrace; P25156; -.
DR Proteomes; UP000001024; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019773; C:proteasome core complex, alpha-subunit complex; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004298; F:threonine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd03756; proteasome_alpha_archeal; 1.
DR Gene3D; 3.60.20.10; -; 1.
DR HAMAP; MF_00289_A; Proteasome_A_A; 1.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR023332; Proteasome_alpha-type.
DR InterPro; IPR019982; Proteasome_asu_arc.
DR InterPro; IPR000426; Proteasome_asu_N.
DR InterPro; IPR001353; Proteasome_sua/b.
DR Pfam; PF00227; Proteasome; 1.
DR Pfam; PF10584; Proteasome_A_N; 1.
DR SMART; SM00948; Proteasome_A_N; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR TIGRFAMs; TIGR03633; arc_protsome_A; 1.
DR PROSITE; PS00388; PROTEASOME_ALPHA_1; 1.
DR PROSITE; PS51475; PROTEASOME_ALPHA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Proteasome;
KW Reference proteome.
FT CHAIN 1..233
FT /note="Proteasome subunit alpha"
FT /id="PRO_0000124189"
FT MUTAGEN 1..12
FT /note="Missing: Markedly increases peptidolytic activity.
FT Designated open-gate mutant."
FT /evidence="ECO:0000269|PubMed:16337593"
FT MUTAGEN 66
FT /note="K->A: Prevents PAN to associate with the proteasome
FT and stimulate gate opening."
FT /evidence="ECO:0000269|PubMed:17803938"
FT MUTAGEN 81
FT /note="L->A,E,G: Prevents PAN to stimulate gate opening."
FT /evidence="ECO:0000269|PubMed:18471981"
FT MUTAGEN 82
FT /note="V->A: No effect on PAN's ability to stimulate gate
FT opening."
FT /evidence="ECO:0000269|PubMed:18471981"
FT MUTAGEN 82
FT /note="V->D,G: Prevents PAN to stimulate gate opening."
FT /evidence="ECO:0000269|PubMed:18471981"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:3J9I"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:6UTI"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1YA7"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:1YAU"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:1YAR"
FT HELIX 82..103
FT /evidence="ECO:0007829|PDB:1YAR"
FT HELIX 109..122
FT /evidence="ECO:0007829|PDB:1YAR"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:1YAU"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:1YAR"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:5VY3"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:1YAR"
FT HELIX 169..179
FT /evidence="ECO:0007829|PDB:1YAR"
FT HELIX 186..199
FT /evidence="ECO:0007829|PDB:1YAR"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1PMA"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:1YAR"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:1YA7"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:1YAR"
SQ SEQUENCE 233 AA; 25799 MW; 141A48581DA0DFB5 CRC64;
MQQGQMAYDR AITVFSPDGR LFQVEYAREA VKKGSTALGM KFANGVLLIS DKKVRSRLIE
QNSIEKIQLI DDYVAAVTSG LVADARVLVD FARISAQQEK VTYGSLVNIE NLVKRVADQM
QQYTQYGGVR PYGVSLIFAG IDQIGPRLFD CDPAGTINEY KATAIGSGKD AVVSFLEREY
KENLPEKEAV TLGIKALKSS LEEGEELKAP EIASITVGNK YRIYDQEEVK KFL
