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Protein

Proteasome-associated ATPase

Gene

mpa

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

ATPase which is responsible for recognizing, binding, unfolding and translocation of pupylated proteins into the bacterial 20S proteasome core particle. May be essential for opening the gate of the 20S proteasome via an interaction with its C-terminus, thereby allowing substrate entry and access to the site of proteolysis. Thus, the C-termini of the proteasomal ATPase may function like a 'key in a lock' to induce gate opening and therefore regulate proteolysis. Is required but not sufficient to confer resistance against the lethal effects of reactive nitrogen intermediates (RNI), antimicrobial molecules produced by activated macrophages and other cell types.UniRule annotation5 Publications

Enzyme regulationi

ATPase activity is inhibited by EDTA, N-ethylmaleimide (NEM) and sodium azide.1 Publication

Kineticsi

  1. KM=330 µM for ATP1 Publication
  1. Vmax=62 pmol/min/µg enzyme1 Publication

pH dependencei

Optimum pH is 7.4-7.5.1 Publication

Pathwayi: proteasomal Pup-dependent pathway

This protein is involved in the pathway proteasomal Pup-dependent pathway, which is part of Protein degradation.UniRule annotation
View all proteins of this organism that are known to be involved in the pathway proteasomal Pup-dependent pathway and in Protein degradation.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi296 – 301ATPUniRule annotation6

GO - Molecular functioni

  • ATPase activity Source: MTBBASE
  • ATP binding Source: UniProtKB-HAMAP
  • proteasome binding Source: MTBBASE
  • ubiquitin-like protein binding Source: UniProtKB

GO - Biological processi

  • modification-dependent protein catabolic process Source: UniProtKB-HAMAP
  • pathogenesis Source: UniProtKB-KW
  • proteasomal protein catabolic process Source: MTBBASE
  • proteasomal ubiquitin-independent protein catabolic process Source: MTBBASE
  • protein unfolding Source: UniProtKB-HAMAP
  • response to nitrosative stress Source: MTBBASE
Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Virulence

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-6321-MONOMER.
UniPathwayiUPA00997.

Names & Taxonomyi

Protein namesi
Recommended name:
Proteasome-associated ATPaseUniRule annotation
Alternative name(s):
AAA ATPase forming ring-shaped complexesUniRule annotation
Short name:
ARCUniRule annotation
Mycobacterial proteasome ATPaseUniRule annotation
Gene namesi
Name:mpaUniRule annotation
Ordered Locus Names:Rv2115c
ORF Names:MTCY261.11c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv2115c.

Subcellular locationi

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • plasma membrane Source: MTBBASE
  • proteasome-activating nucleotidase complex Source: MTBBASE
Complete GO annotation...

Keywords - Cellular componenti

Proteasome

Pathology & Biotechi

Disruption phenotypei

Cells lacking this gene accumulate pupylated proteins. These cells also become hypersensitive to reactive nitrogen intermediates (RNI) and are severely attenuated in both wild-type and nitric oxide synthase 2 deficient mice. Moreover, they display increased resistance to hydrogen peroxide.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120R → A: Does not dramatically affect proteasome substrate degradation. 1 Publication1
Mutagenesisi173R → E: Impairs Mpa hexamerization; when associated with A-187 and E-235. 1 Publication1
Mutagenesisi187W → A: Impairs Mpa hexamerization; when associated with E-173 and E-235. 1 Publication1
Mutagenesisi225K → A: Does not dramatically affect proteasome substrate degradation. 1 Publication1
Mutagenesisi235K → E: Impairs Mpa hexamerization; when associated with E-173 and A-187. 1 Publication1
Mutagenesisi299K → Q: Reduces both ATPase activity and ATP affinity. Abolishes proteasome substrate degradation and protection against RNI. 2 Publications1
Mutagenesisi341F → A: Abolishes unfolding capacity. 1 Publication1
Mutagenesisi341F → Y: No effect on unfolding capacity. 1 Publication1
Mutagenesisi342V → A: Abolishes proteasome substrate degradation. 1 Publication1
Mutagenesisi371D → A: Severely reduces ATPase activity. Abolishes proteasome substrate degradation and protection against RNI. 2 Publications1
Mutagenesisi372E → A: Severely reduces ATPase activity. Abolishes protection against RNI. 1 Publication1
Mutagenesisi372E → Q: Abolishes protection against RNI. 1 Publication1
Mutagenesisi608 – 609Missing : Retains ATPase and unfolding activities, yet abolishes proteasome substrate degradation and protection against RNI. Is also highly attenuated in mice. 3 Publications2
Mutagenesisi608Y → E or F: Abolishes proteasome substrate degradation and protection against RNI. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000847781 – 609Proteasome-associated ATPaseAdd BLAST609

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki591Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-Cter in protein Pup)1 Publication

Post-translational modificationi

Pupylated at Lys-591 by the prokaryotic ubiquitin-like protein Pup, which leads to its degradation by the proteasome. Mpa thus promotes its own turnover.1 Publication
Mpa is a target of RNI, thereby is S-nitrosylated in the phagosome of immunologically activated host macrophages, which causes enzyme inhibition.1 Publication

Keywords - PTMi

Isopeptide bond, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiP9WQN5.

Interactioni

Subunit structurei

Homohexamer. Assembles into a hexameric ring structure that caps the 20S proteasome core. Strongly interacts with the prokaryotic ubiquitin-like protein Pup through a hydrophobic interface; the interacting region of Mpa lies in its N-terminal coiled-coil domain. There is one Pup binding site per Mpa hexamer ring; the K(D) measured is about 3.8 µM. Upon ATP-binding, the C-terminus of Mpa interacts with the alpha-rings of the proteasome core, possibly by binding to the intersubunit pockets.UniRule annotation7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
pupP9WHN53EBI-7241067,EBI-7241023

GO - Molecular functioni

  • proteasome binding Source: MTBBASE
  • ubiquitin-like protein binding Source: UniProtKB

Protein-protein interaction databases

IntActiP9WQN5. 1 interactor.
STRINGi83332.Rv2115c.

Structurei

Secondary structure

1609
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi53 – 94Combined sources42
Beta strandi99 – 107Combined sources9
Beta strandi109 – 117Combined sources9
Beta strandi120 – 126Combined sources7
Beta strandi140 – 143Combined sources4
Beta strandi149 – 152Combined sources4
Beta strandi158 – 167Combined sources10
Beta strandi171 – 177Combined sources7
Beta strandi183 – 188Combined sources6
Helixi190 – 193Combined sources4
Helixi203 – 205Combined sources3
Beta strandi219 – 223Combined sources5
Turni224 – 227Combined sources4
Beta strandi228 – 233Combined sources6
Helixi238 – 245Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FP9X-ray2.00A/B/C/D/E/F/G/H/I/J/K/L98-245[»]
3M91X-ray1.80A/C46-96[»]
3M9BX-ray3.94A/B/C/D/E/F/G/H/I/J/K/L1-234[»]
3M9DX-ray4.50A/B/C/D/E/F/J/K/L/M/N/O1-234[»]
3M9HX-ray2.00A/B/C/D/E/F46-96[»]
ProteinModelPortaliP9WQN5.
SMRiP9WQN5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni608 – 609Docks into pockets in the proteasome alpha-ringUniRule annotation2

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili20 – 96UniRule annotationAdd BLAST77

Domaini

Consists of three main regions, an N-terminal coiled-coil domain (residues 1-96) that binds to protein Pup and functions as a docking station, an interdomain (residues 97-245) involved in Mpa hexamerization, and a C-terminal ATPase domain of the AAA type (residues 246-609).3 Publications

Sequence similaritiesi

Belongs to the AAA ATPase family.UniRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG4105DHM. Bacteria.
COG0464. LUCA.
KOiK13527.
OMAiCVDEFKE.
PhylomeDBiP9WQN5.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_02112. ARC_ATPase. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR027417. P-loop_NTPase.
IPR032501. Prot_ATP_ID_OB.
IPR022482. Proteasome_ATPase.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF16450. Prot_ATP_ID_OB. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
TIGRFAMsiTIGR03689. pup_AAA. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P9WQN5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGESERSEAF GIPRDSPLSS GDAAELEQLR REAAVLREQL ENAVGSHAPT
60 70 80 90 100
RSARDIHQLE ARIDSLAARN SKLMETLKEA RQQLLALREE VDRLGQPPSG
110 120 130 140 150
YGVLLATHDD DTVDVFTSGR KMRLTCSPNI DAASLKKGQT VRLNEALTVV
160 170 180 190 200
EAGTFEAVGE ISTLREILAD GHRALVVGHA DEERVVWLAD PLIAEDLPDG
210 220 230 240 250
LPEALNDDTR PRKLRPGDSL LVDTKAGYAF ERIPKAEVED LVLEEVPDVS
260 270 280 290 300
YADIGGLSRQ IEQIRDAVEL PFLHKELYRE YSLRPPKGVL LYGPPGCGKT
310 320 330 340 350
LIAKAVANSL AKKMAEVRGD DAHEAKSYFL NIKGPELLNK FVGETERHIR
360 370 380 390 400
LIFQRAREKA SEGTPVIVFF DEMDSIFRTR GTGVSSDVET TVVPQLLSEI
410 420 430 440 450
DGVEGLENVI VIGASNREDM IDPAILRPGR LDVKIKIERP DAEAAQDIYS
460 470 480 490 500
KYLTEFLPVH ADDLAEFDGD RSACIKAMIE KVVDRMYAEI DDNRFLEVTY
510 520 530 540 550
ANGDKEVMYF KDFNSGAMIQ NVVDRAKKNA IKSVLETGQP GLRIQHLLDS
560 570 580 590 600
IVDEFAENED LPNTTNPDDW ARISGKKGER IVYIRTLVTG KSSSASRAID

TESNLGQYL
Length:609
Mass (Da):67,401
Last modified:April 16, 2014 - v1
Checksum:i4D5F4E630614C58D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ888314 Genomic DNA. Translation: ABI36485.1.
AL123456 Genomic DNA. Translation: CCP44890.1.
PIRiF70512.
RefSeqiNP_216631.1. NC_000962.3.
WP_003411035.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP44890; CCP44890; Rv2115c.
GeneIDi887297.
KEGGimtu:Rv2115c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ888314 Genomic DNA. Translation: ABI36485.1.
AL123456 Genomic DNA. Translation: CCP44890.1.
PIRiF70512.
RefSeqiNP_216631.1. NC_000962.3.
WP_003411035.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FP9X-ray2.00A/B/C/D/E/F/G/H/I/J/K/L98-245[»]
3M91X-ray1.80A/C46-96[»]
3M9BX-ray3.94A/B/C/D/E/F/G/H/I/J/K/L1-234[»]
3M9DX-ray4.50A/B/C/D/E/F/J/K/L/M/N/O1-234[»]
3M9HX-ray2.00A/B/C/D/E/F46-96[»]
ProteinModelPortaliP9WQN5.
SMRiP9WQN5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP9WQN5. 1 interactor.
STRINGi83332.Rv2115c.

Proteomic databases

PaxDbiP9WQN5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP44890; CCP44890; Rv2115c.
GeneIDi887297.
KEGGimtu:Rv2115c.

Organism-specific databases

TubercuListiRv2115c.

Phylogenomic databases

eggNOGiENOG4105DHM. Bacteria.
COG0464. LUCA.
KOiK13527.
OMAiCVDEFKE.
PhylomeDBiP9WQN5.

Enzyme and pathway databases

UniPathwayiUPA00997.
BioCyciMTBH37RV:G185E-6321-MONOMER.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_02112. ARC_ATPase. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR027417. P-loop_NTPase.
IPR032501. Prot_ATP_ID_OB.
IPR022482. Proteasome_ATPase.
[Graphical view]
PfamiPF00004. AAA. 1 hit.
PF16450. Prot_ATP_ID_OB. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
TIGRFAMsiTIGR03689. pup_AAA. 1 hit.
PROSITEiPS00674. AAA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARC_MYCTU
AccessioniPrimary (citable) accession number: P9WQN5
Secondary accession number(s): L0T8W3
, O33250, P63345, Q0G9Y7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: November 2, 2016
This is version 20 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Was identified as a natural substrate of the M.tuberculosis proteasome.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.