Gene - combatTB X

mpa

Type: protein_coding
Name: mpa
Locus Name: Rv2115c
Product: Mycobacterial proteasome ATPase Mpa
Functional Category: Cell wall and cell processes
Location: 2374461..2376290 (- strand)
Gene Length: 1829 bp
Nucleotides: ATGGGTGAGTCAGAGCGTTCTGAGGCATTCGGCATCCCCCGGGATAGCCCGCTGTCCAGTGGTGATGCCGCCGAATTAGAACAGCTGCGGCGCGAGGCTGCGGTCCTGCGCGAGCAACTTGAGAACGCCGTCGGATCACATGCCCCGACGCGCTCTGCCCGCGATATACATCAACTCGAAGCCCGTATCGACTCACTTGCTGCCCGCAATTCCAAATTAATGGAAACTCTTAAAGAAGCCCGTCAACAACTGCTGGCGCTGCGCGAGGAAGTTGACCGGCTGGGGCAGCCGCCCAGTGGCTACGGCGTCCTGCTGGCCACGCACGACGACGACACGGTCGATGTGTTCACATCGGGTCGCAAGATGCGCCTGACGTGCTCACCGAATATTGACGCTGCATCGCTGAAGAAGGGGCAGACGGTCCGGCTCAACGAGGCCCTGACCGTCGTGGAGGCCGGCACATTCGAGGCGGTCGGCGAGATATCCACCTTGCGCGAGATCCTGGCCGACGGTCATCGGGCTCTGGTCGTCGGCCACGCCGACGAGGAACGCGTTGTTTGGCTGGCTGATCCCCTGATCGCCGAGGACCTGCCAGACGGCCTCCCTGAGGCCCTCAACGATGACACCCGGCCGCGCAAGCTGCGCCCCGGCGACTCGCTGCTGGTCGACACCAAAGCCGGCTATGCCTTCGAACGCATCCCCAAAGCCGAGGTAGAAGACCTGGTGCTGGAAGAGGTGCCGGACGTCAGCTACGCCGACATCGGCGGTCTGAGCCGCCAGATCGAGCAGATCCGCGACGCCGTGGAGCTGCCGTTCCTGCACAAGGAGTTGTACCGGGAGTACTCGCTGCGCCCGCCCAAGGGTGTGTTGCTCTATGGCCCACCCGGCTGTGGTAAGACGTTGATCGCCAAGGCTGTGGCCAACTCGTTGGCCAAGAAAATGGCCGAGGTCCGCGGCGACGATGCCCACGAGGCGAAGTCGTACTTCCTCAACATCAAGGGCCCCGAGCTGCTGAACAAATTCGTCGGGGAAACGGAACGCCACATCCGGCTGATCTTCCAACGGGCCCGCGAGAAGGCGTCGGAAGGCACTCCGGTGATCGTGTTTTTCGACGAGATGGACTCGATCTTTCGCACCCGTGGCACCGGCGTTTCCTCGGACGTCGAGACCACGGTGGTCCCGCAGCTGCTCAGCGAGATCGACGGGGTGGAGGGACTCGAGAATGTCATCGTGATCGGCGCCTCCAACCGAGAGGACATGATCGACCCTGCCATCCTGCGGCCCGGGCGCCTCGACGTGAAGATCAAGATCGAGCGGCCTGATGCCGAAGCGGCGCAGGACATCTACTCGAAGTACCTGACCGAGTTCTTGCCGGTGCACGCCGACGATCTCGCCGAGTTCGACGGTGACCGTTCGGCCTGCATCAAGGCGATGATCGAGAAGGTTGTCGACCGGATGTATGCCGAGATCGACGACAACCGGTTCCTGGAGGTCACCTATGCCAACGGCGACAAGGAAGTCATGTACTTCAAGGACTTCAACTCCGGGGCGATGATCCAGAACGTCGTCGACCGAGCCAAGAAGAACGCCATCAAATCGGTGCTGGAGACCGGCCAACCGGGACTGCGTATACAGCATCTGCTCGATTCGATCGTCGACGAGTTCGCCGAGAACGAGGATTTGCCCAACACCACCAACCCCGATGACTGGGCGCGGATCTCGGGCAAGAAGGGGGAGCGGATCGTCTACATCCGCACCCTGGTCACCGGAAAGAGTTCGTCGGCCAGCAGGGCTATTGATACCGAGTCCAACCTCGGCCAGTACCTGTA
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

Function

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. {ECO:0000255|HAMAP-Rule:MF_02112, ECO:0000269|PubMed:14671303, ECO:0000269|PubMed:15659170, ECO:0000269|PubMed:17082771, ECO:0000269|PubMed:19836337, ECO:0000269|PubMed:20203624}.

Family

AAA ATPase family

GO

ubiquitination-like modification-dependent protein binding GO:0140035 molecular_function
proteasomal protein catabolic process GO:0010498 biological_process
proteasomal ubiquitin-independent protein catabolic process GO:0010499 biological_process
cellular response to nitric oxide GO:0071732 biological_process
proteasome-activating nucleotidase complex GO:0022623 cellular_component
pathogenesis GO:0009405 biological_process
modification-dependent protein catabolic process GO:0019941 biological_process
proteasome binding GO:0070628 molecular_function
protein unfolding GO:0043335 biological_process
ATPase activity GO:0016887 molecular_function
response to nitrosative stress GO:0051409 biological_process
plasma membrane GO:0005886 cellular_component
identical protein binding GO:0042802 molecular_function
ATP binding GO:0005524 molecular_function
cell wall GO:0005618 cellular_component

InterPro

UniProt: P9WQN5
GenBank: Rv2115c
EnsemblBacteria: Rv2115c
Mycobrowser: Rv2115c

PDB IDs:

Summary

Name: Proteasome-associated ATPase (AAA ATPase forming ring-shaped complexes) (ARC) (Mycobacterial proteasome ATPase)
Family: AAA ATPase family
Protein Sequence: MGESERSEAFGIPRDSPLSSGDAAELEQLRREAAVLREQLENAVGSHAPTRSARDIHQLEARIDSLAARNSKLMETLKEARQQLLALREEVDRLGQPPSGYGVLLATHDDDTVDVFTSGRKMRLTCSPNIDAASLKKGQTVRLNEALTVVEAGTFEAVGEISTLREILADGHRALVVGHADEERVVWLADPLIAEDLPDGLPEALNDDTRPRKLRPGDSLLVDTKAGYAFERIPKAEVEDLVLEEVPDVSYADIGGLSRQIEQIRDAVELPFLHKELYREYSLRPPKGVLLYGPPGCGKTLIAKAVANSLAKKMAEVRGDDAHEAKSYFLNIKGPELLNKFVGETERHIRLIFQRAREKASEGTPVIVFFDEMDSIFRTRGTGVSSDVETTVVPQLLSEIDGVEGLENVIVIGASNREDMIDPAILRPGRLDVKIKIERPDAEAAQDIYSKYLTEFLPVHADDLAEFDGDRSACIKAMIEKVVDRMYAEIDDNRFLEVTYANGDKEVMYFKDFNSGAMIQNVVDRAKKNAIKSVLETGQPGLRIQHLLDSIVDEFAENEDLPNTTNPDDWARISGKKGERIVYIRTLVTGKSSSASRAIDTESNLGQYL
Mass: 67,401 Da
Length: 609 Aa

Rv2115c doesn't seem to be a targeted by any drug.

Rv2115c doesn't seem to be involved in any pathway.

Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa.: Structure. 2009 Oct 14;17(10):1377-85. doi: 10.1016/j.str.2009.08.010.
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.
Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected] .: PLoS One. 2010 Jan 6;5(1):e8589. doi: 10.1371/journal.pone.0008589.
The mycobacterial Mpa-proteasome unfolds and degrades pupylated substrates by engaging Pup's N-terminus.: EMBO J. 2010 Apr 7;29(7):1262-71. doi: 10.1038/emboj.2010.23. Epub 2010 Mar 4.
Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes.: Nat Struct Mol Biol. 2009 Jun;16(6):647-51. doi: 10.1038/nsmb.1597. Epub 2009 May 17.
Prokaryotic ubiquitin-like protein pup is intrinsically disordered.: J Mol Biol. 2009 Sep 11;392(1):208-17. doi: 10.1016/j.jmb.2009.07.018. Epub 2009 Jul 14.
A distinct structural region of the prokaryotic ubiquitin-like protein (Pup) is recognized by the N-terminal domain of the proteasomal ATPase Mpa.: FEBS Lett. 2009 Oct 6;583(19):3151-7. doi: 10.1016/j.febslet.2009.09.020. Epub 2009 Sep 15.
Pup, a prokaryotic ubiquitin-like protein, is an intrinsically disordered protein.: Biochem J. 2009 Aug 13;422(2):207-15. doi: 10.1042/BJ20090738.
Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis.: Science. 2008 Nov 14;322(5904):1104-7. doi: 10.1126/science.1163885. Epub 2008 Oct 2.
Identification of substrates of the Mycobacterium tuberculosis proteasome.: EMBO J. 2006 Nov 15;25(22):5423-32. doi: 10.1038/sj.emboj.7601405. Epub 2006 Nov 2.
S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense.: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):467-72. doi: 10.1073/pnas.0406133102. Epub 2004 Dec 30.
The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide.: Science. 2003 Dec 12;302(5652):1963-6. doi: 10.1126/science.1091176.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.
Characterization of a Mycobacterium tuberculosis proteasomal ATPase homologue.: Mol Microbiol. 2005 Jan;55(2):561-71. doi: 10.1111/j.1365-2958.2004.04403.x.