P25156 (PSA_THEAC) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteasome subunit alpha
EC=3.4.25.1

Alternative name(s):
20S proteasome alpha subunit
Proteasome core protein PsmA

Gene names

Name:	psmA
Ordered Locus Names:	Ta1288

Organism

Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)

Taxonomic identifier

273075 [NCBI]

Taxonomic lineage

Archaea › Euryarchaeota › Thermoplasmata › Thermoplasmatales › Thermoplasmataceae › Thermoplasma

Protein attributes

Sequence length	233 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The T.acidophilum proteasome is able to cleave oligopeptides after Tyr, Leu, Phe, and to a lesser extent after Glu and Arg. Thus, displays chymotrypsin-like activity and low level of caspase-like and trypsin-like activities. Ref.4
Catalytic activity	Cleavage of peptide bonds with very broad specificity. Ref.4
Enzyme regulation	The formation of the proteasomal ATPase PAN-20S proteasome complex, via the docking of the C-termini of PAN into the intersubunit pockets in the alpha-rings, triggers opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity. Ref.8 Ref.14
Subunit structure	The 20S proteasome core is composed of 14 alpha and 14 beta subunits that assemble into four stacked heptameric rings, resulting in a barrel-shaped structure. The two inner rings, each composed of seven catalytic beta subunits, are sandwiched by two outer rings, each composed of seven alpha subunits. The catalytic chamber with the active sites is on the inside of the barrel. Has a gated structure, the ends of the cylinder being occluded by the N-termini of the alpha-subunits. Is capped at one or both ends by the proteasome regulatory ATPase, PAN. Ref.5 Ref.7 Ref.9 Ref.10 Ref.12 Ref.13
Subcellular location	Cytoplasm By similarity HAMAP MF_00289_A.
Post-translational modification	The N-terminus is blocked. HAMAP MF_00289_A
Miscellaneous	The configuration of the closed gate contains an opening large enough to allow rapid entry of tetrapeptides but able to impede the entry of proteins and longer peptides. HAMAP MF_00289_A
Sequence similarities	Belongs to the peptidase T1A family.
Biophysicochemical properties	Kinetic parameters: KM=39 µM for Suc-LLVY-Amc (at 55 degrees Celsius) Ref.4 Vmax=28 nmol/min/mg enzyme with Suc-LLVY-Amc as substrate (at 55 degrees Celsius)

Ontologies

Keywords
Cellular component	Cytoplasm Proteasome
Molecular function	Hydrolase Protease Threonine protease
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	proteasomal protein catabolic process Inferred from direct assay Ref.4. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell proteasome core complex, alpha-subunit complex Inferred from direct assay Ref.12Ref.9Ref.4. Source: UniProtKB
Molecular function	threonine-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 233

233

Proteasome subunit alpha HAMAP MF_00289_A

PRO_0000124189

Experimental info

Mutagenesis

1 – 12

12

Missing: Markedly increases peptidolytic activity. Designated open-gate mutant. Ref.7

Mutagenesis

66

1

K → A: Prevents PAN to associate with the proteasome and stimulate gate opening. Ref.8

Mutagenesis

81

1

L → A, E or G: Prevents PAN to stimulate gate opening. Ref.11

Mutagenesis

82

1

V → A: No effect on PAN's ability to stimulate gate opening. Ref.11

Mutagenesis

82

1

V → D or G: Prevents PAN to stimulate gate opening. Ref.11

Secondary structure

1

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233

Helix Strand Turn

Details...

Helix

22 – 31

10

Beta strand

37 – 42

6

Beta strand

45 – 50

6

Beta strand

57 – 59

3

Beta strand

66 – 71

6

Beta strand

74 – 81

8

Helix

82 – 103

22

Helix

109 – 122

14

Turn

123 – 125

3

Beta strand

134 – 141

8

Beta strand

146 – 151

6

Beta strand

157 – 166

10

Helix

169 – 179

11

Helix

186 – 199

14

Beta strand

211 – 216

6

Beta strand

222 – 224

3

Helix

226 – 230

5

Sequences

	Sequence		Length	Mass (Da)
	P25156 [UniParc]. Last modified October 1, 1994. Version 2. Checksum: 141A48581DA0DFB5	FASTA	233	25,799
	10 20 30 40 50 60 MQQGQMAYDR AITVFSPDGR LFQVEYAREA VKKGSTALGM KFANGVLLIS DKKVRSRLIE 70 80 90 100 110 120 QNSIEKIQLI DDYVAAVTSG LVADARVLVD FARISAQQEK VTYGSLVNIE NLVKRVADQM 130 140 150 160 170 180 QQYTQYGGVR PYGVSLIFAG IDQIGPRLFD CDPAGTINEY KATAIGSGKD AVVSFLEREY 190 200 210 220 230 KENLPEKEAV TLGIKALKSS LEEGEELKAP EIASITVGNK YRIYDQEEVK KFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of the gene encoding the large (alpha-) subunit of the proteasome from Thermoplasma acidophilum." Zwickl P., Lottspeich F., Dahlmann B., Baumeister W. FEBS Lett. 278:217-221(1991) [PubMed: 1991516] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 21-28; 41-54 AND 88-93.
[2]	Zwickl P. Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 66-69.
[3]	"The genome sequence of the thermoacidophilic scavenger Thermoplasma acidophilum." Ruepp A., Graml W., Santos-Martinez M.-L., Koretke K.K., Volker C., Mewes H.-W., Frishman D., Stocker S., Lupas A.N., Baumeister W. Nature 407:508-513(2000) [PubMed: 11029001] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165.
[4]	"Processive degradation of proteins and other catalytic properties of the proteasome from Thermoplasma acidophilum." Akopian T.N., Kisselev A.F., Goldberg A.L. J. Biol. Chem. 272:1791-1798(1997) [PubMed: 8999862] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS.
[5]	"Subunit stoichiometry and three-dimensional arrangement in proteasomes from Thermoplasma acidophilum." Puehler G., Weinkauf S., Bachmann L., Mueller S., Engel E., Hegerl R., Baumeister W. EMBO J. 11:1607-1616(1992) [PubMed: 1373380] [Abstract] Cited for: SUBUNIT.
[6]	"Range of sizes of peptide products generated during degradation of different proteins by archaeal proteasomes." Kisselev A.F., Akopian T.N., Goldberg A.L. J. Biol. Chem. 273:1982-1989(1998) [PubMed: 9442034] [Abstract] Cited for: CHARACTERIZATION.
[7]	"ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins." Smith D.M., Kafri G., Cheng Y., Ng D., Walz T., Goldberg A.L. Mol. Cell 20:687-698(2005) [PubMed: 16337593] [Abstract] Cited for: INTERACTION WITH PAN, SUBUNIT, GATED STRUCTURE, MUTAGENESIS OF 1-MET--ILE-12.
[8]	"Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry." Smith D.M., Chang S.C., Park S., Finley D., Cheng Y., Goldberg A.L. Mol. Cell 27:731-744(2007) [PubMed: 17803938] [Abstract] Cited for: GATE OPENING MECHANISM, ENZYME REGULATION, MUTAGENESIS OF LYS-66.
[9]	"Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4-A resolution." Lowe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. Science 268:533-539(1995) [PubMed: 7725097] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT, SUBUNIT.
[10]	"The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions." Forster A., Masters E.I., Whitby F.G., Robinson H., Hill C.P. Mol. Cell 18:589-599(2005) [PubMed: 15916965] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT AND T.BRUCEI PA26.
[11]	"Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases." Rabl J., Smith D.M., Yu Y., Chang S.C., Goldberg A.L., Cheng Y. Mol. Cell 30:360-368(2008) [PubMed: 18471981] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (6.8 ANGSTROMS) OF THE OPEN-GATE AND CLOSED-GATE CONFORMATIONS, GATE OPENING MECHANISM, MUTAGENESIS OF LEU-81 AND VAL-82.
[12]	"Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions." Yu Y., Smith D.M., Kim H.M., Rodriguez V., Goldberg A.L., Cheng Y. EMBO J. 29:692-702(2010) [PubMed: 20019667] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEX WITH THE BETA SUBUNIT AND THE C-TERMINUS OF PAN FROM M.JANNASCHII.
[13]	"Structural models for interactions between the 20S proteasome and its PAN/19S activators." Stadtmueller B.M., Ferrell K., Whitby F.G., Heroux A., Robinson H., Myszka D.G., Hill C.P. J. Biol. Chem. 285:13-17(2010) [PubMed: 19889631] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT AND CHIMERIC PA26 CONSTRUCTS.
[14]	"Dynamic regulation of archaeal proteasome gate opening as studied by TROSY NMR." Religa T.L., Sprangers R., Kay L.E. Science 328:98-102(2010) [PubMed: 20360109] [Abstract] Cited for: STRUCTURE BY NMR, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X59507 Genomic DNA. Translation: CAA42094.1.
AL445067 Genomic DNA. Translation: CAC12411.1.

PIR

S55350.

RefSeq

NP_394744.1. NC_002578.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PMA	X-ray	3.40	A/C/D/E/F/G/H/I/J/K/L/M/N/O	1-233	[»]
1YA7	X-ray	2.30	A/B/C/D/E/F/G	1-233	[»]
1YAR	X-ray	1.90	A/B/C/D/E/F/G	1-233	[»]
1YAU	X-ray	2.40	A/B/C/D/E/F/G	1-233	[»]
2KU1	NMR	-	A/B/C/D/E/F/G	1-233	[»]
2KU2	NMR	-	A/B/C/D/E/F/G	1-233	[»]
3C91	electron microscopy	6.80	A/B/C/D/E/F/G/O/P/Q/R/S/T/U	1-233	[»]
3C92	electron microscopy	6.80	A/B/C/D/E/F/G/O/P/Q/R/S/T/U	1-233	[»]
3IPM	X-ray	4.00	A/B/C/D/E/F/G	1-233	[»]
3JRM	X-ray	2.90	A/B/C/D/E/F/G	7-233	[»]
3JSE	X-ray	2.90	A/B/C/D/E/F/G	7-233	[»]
3JTL	X-ray	3.20	A/B/C/D/E/F/G	7-233	[»]

ProteinModelPortal

P25156.

SMR

P25156. Positions 7-233.

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

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Genome annotation databases

GeneID

1456771.

GenomeReviews

Gene locus Ta1288 in contig AL139299_GR.

KEGG

tac:Ta1288.

NMPDR

fig|273075.1.peg.1266.

Phylogenomic databases

HOGENOM

HBG499923.

OMA

FQVEYAR.

PhylomeDB

P25156.

ProtClustDB

PRK03996.

Enzyme and pathway databases

BioCyc

TACI273075:TA1288-MONOMER.

Family and domain databases

HAMAP

MF_00289_A. Proteasome_A_A.
[Tree]

InterPro

IPR019982. Proteasome_asu_arc.
IPR000426. Proteasome_asu_N.
IPR023332. Proteasome_suA-type.
IPR001353. Proteasome_sua/b.
[Graphical view]

KO

K03432.

Pfam

PF00227. Proteasome. 1 hit.
PF10584. Proteasome_A_N. 1 hit.
[Graphical view]

SMART

SM00948. Proteasome_A_N. 1 hit.
[Graphical view]

TIGRFAMs

TIGR03633. Arc_protsome_A. 1 hit.

PROSITE

PS00388. PROTEASOME_A_1. 1 hit.
PS51475. PROTEASOME_A_2. 1 hit.
[Graphical view]

ProtoNet

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Entry information

Entry name

PSA_THEAC

Accession

Primary (citable) accession number: P25156

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	October 1, 1994
Last modified:	January 25, 2012
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program