P9WMK7 · DBH_MYCTU

Function

function

A nucleoid-associated protein (NAP) that probably plays a role in chromosome compactation. Binds DNA non-specifically, with greater affinity for supercoiled than linear DNA, binds well to nicked DNA, gapped and cruciform DNA. Has a preference for A:T rich DNA (PubMed:10645441, PubMed:20824060).
Required for activation of the mtbB operon. Binds the mtbB promoter in the presence of iron, binding is seen with as little as 25 uM Fe2+ and increases with increasing Fe2+ (PubMed:24610707).
RNase E and HupB jointly contribute to cellular adaptation to changing growth conditions and survival during antibiotic treatment and in the host (PubMed:35521527).
Plays a role in stress survival (PubMed:36071978).
Stimulates supercoiling relaxation by topoisomerase 1 (Top1, topA) (By similarity).
Binds Fe3+ but not Fe2+. Has ferroxidase activity, converts Fe2+ into Fe3+ and in the presence of H2O2 prevents the generation of hydroxyl radicals (the Fenton reaction). Protects DNA from damage in the presence of FeSO4 and H2O2. May function in iron storage (PubMed:21698192).
Involved in iron uptake by bacteria (either Fe3+ or extracellular carboxymycobactin); antibodies against HupB block uptake of both. Following uptake iron is mostly found in the iron siderophores carboxymycobactin (CMb, extracellular) or mycobactin (Mb, lipophilic). Facilitates transfer of iron from CMb to Mb when liposomes plus a cell wall lysate are incubated with CMb. Binds iron, ferri-CMb and ferri-Mb; has 10-fold higher affinity for ferri-Mb. Suggested to transfer iron from CBm to Mb at the cell membrane (PubMed:33609202).
Required for biofilm formation; trimethylation by recombinant human SUV39H1 (a histone methyltransferase) inhibits biofilm formation (PubMed:29170282).
Induces lymphoproliferation, particularly in health tuberculin reactors, and is immunogenic (PubMed:10645441).
Maybe involved in pathogenesis of inflammatory bowel disease (IBD) in patients with ulcerative colitis and Crohn disease (CD). Bound by anti-neutrophil cytoplasmic antibodies (pANCA), which are a hallmark of IBD. The binding is due to pANCA directed against H1-3 cross-reacting with DBH epitopes. In CD, target of a strong IgA response (PubMed:10569769).
May play a role in cell wall assembly (Probable) (PubMed:17873049).
In vitro at low levels enhances formation of TMM and TDM by antigen 85 proteins (fbpA, fbpB, fbpC), at higher levels inhibits TMM and TDM formation (Probable) (PubMed:17873049).

Miscellaneous

Was identified as a high-confidence drug target.

Caution

The revised start codon for the 216-residue version of this protein is GTT.

Catalytic activity

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.252 mMFe2+

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentextracellular region
Cellular Componentnucleoid
Cellular Componentpeptidoglycan-based cell wall
Cellular Componentplasma membrane
Cellular Componentprotein-DNA complex
Molecular Functiondamaged DNA binding
Molecular FunctionDNA binding
Molecular FunctionDNA-binding transcription activator activity
Molecular Functiondouble-stranded DNA binding
Molecular Functionferric iron binding
Molecular Functionferroxidase activity
Molecular Functionstructural constituent of chromatin
Molecular Functionsupercoiled DNA binding
Molecular Functiontranscription cis-regulatory region binding
Biological Processbiofilm matrix assembly
Biological Processcell wall organization
Biological Processcellular response to iron ion starvation
Biological Processchromosome condensation
Biological ProcessDNA protection
Biological Processiron ion transport
Biological Processnucleoid organization
Biological Processpositive regulation of DNA-templated transcription

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    DNA-binding protein HupB
  • EC number
  • Short names
    HupB
  • Alternative names
    • 28 kDa iron-regulated protein
      (Irep-28
      )
    • DNA-binding protein HU homolog
    • Histone H1 homolog
    • Histone-like protein
      (HLPMt
      ; Hlp
      )
    • Nucleoid-associated protein HU

Gene names

    • Name
      hupB
    • Synonyms
      hlp
      , hup, lbp21
    • ORF names
      MTCY349.01
    • Ordered locus names
      Rv2986c

Organism names

  • Taxonomic identifier
  • Strains
    • ATCC 35801 / TMC 107 / Erdman
    • ATCC 25618 / H37Rv
    • H37Rv
    • ATCC 27294 / TMC 102 / H37Rv
  • Taxonomic lineage
    Bacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium tuberculosis complex

Accessions

  • Primary accession
    P9WMK7
  • Secondary accessions
    • L0TBG2
    • P95109

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, nucleoid
Secreted, cell wall
Note: Found along the cell length in a bead-like pattern (probably associated with DNA) (PubMed:35521527).
Only seen in the cell wall when grown under low iron conditions (PubMed:33609202).

Keywords

Phenotypes & Variants

Disruption phenotype

Pronounced lag-phase during growth; the lag is greater in low iron conditions (0.02 ug Fe/ml). 3 to 5-fold decreases in expression of iron siderophores mycobactin and carboxymycobactin in low iron media. Altered expression of a number of genes, including decreased expression of some involved in iron homeostasis (PubMed:24610707).
Bacteria do not take up iron either as Fe3+ or as carboxymycobactin (PubMed:33609202).
Bacteria do not survive in mouse macrophages (PubMed:24610707, PubMed:29170282).
Does not form biofilm (PubMed:29170282).
Much slower growth in rich medium, greatly increased sensitivity to all stresses, death at low pH, oxidative and nitrosative stress, greatly decreased uptake by and survival in human macrophages, increased sensitivity to INH and rifampicin, greatly increased sensitivity to 0.05% SDS, enhanced permeability of the cell membrane due to decreased expression of polyketide synthases including ppsA, ppsC, and ppsE, downregulates DrrA efflux pump expression (PubMed:36071978).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis140Significantly decreased trimethylation of HupB by host SUV39H1, increased bacterial survival in human macrophages, SUV39H1 no longer inhibits biofilm formation.
Mutagenesis185No change in trimethylation by human SUV39H1.
Mutagenesis216No change in trimethylation by human SUV39H1.

PTM/Processing

Features

Showing features for initiator methionine, propeptide, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed
PropeptidePRO_00004553882Removed; alternate
ChainPRO_00001049502-216DNA-binding protein HupB
Modified residue3N-acetylmethionine
ChainPRO_00004553893-216DNA-binding protein HupB, propeptide removed
Modified residue5N6-acetyllysine
Modified residue74N6-acetyllysine
Modified residue88N6-acetyllysine
Modified residue105N6-acetyllysine
Modified residue118N6-acetyllysine
Modified residue135N6-acetyllysine
Modified residue140N6,N6,N6-trimethyllysine
Modified residue148N6-acetyllysine
Modified residue169N6-acetyllysine

Post-translational modification

Probably acetylated by Eis in vivo (By similarity).
In vitro acetylated by Eis (strain H37Rv and H37Ra) on many more residues than those identified in vivo (PubMed:29345920).
Deacetylated in vitro by NAD-dependent protein deacylase (Rv1151c) (PubMed:29345920).
Trimethylated on Lys-140 by human SUV39H1; trimethylation inhibits mycobacterial growth. SUV39H1 probably also trimethylates another residue (PubMed:29170282).
Probably succinylated by Rv0802c and desuccinylated by NAD-dependent protein deacylase (Rv1151c).

Keywords

Proteomic databases

PTM databases

Expression

Induction

Increased expression under iron limitation (at protein level) (PubMed:17028216, PubMed:24610707).
Expressed at all growth phases in rich and minial medium; more protein in mid- to late-log and stationary phases (at protein level). Increased expression under oxidative stress or growth on isoniazid (INH), decreased expression under nitrosative or acidic stress, or growth on rifampicin (at protein level) (PubMed:36071978).

Gene expression databases

Interaction

Subunit

Oligomerizes (By similarity).
Interacts with topoisomerase 1 (topA) (By similarity).
Interacts with Eis (By similarity).
Interacts with antigen 85 proteins (fbpA, fbpB, fbpC) (Probable) (PubMed:17873049).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, compositional bias.

TypeIDPosition(s)Description
Region3-92Bacterial histone-like domain
Region102-216Disordered
Region103-216Degenerate repeats region
Compositional bias117-134Basic residues
Compositional bias162-179Basic residues

Domain

The highly basic C-terminus confers greater specificity in DNA binding to all tested dsDNA (PubMed:20824060).
Residues 1-102 stimulate Top1 and physically interact with it (By similarity).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    216
  • Mass (Da)
    22,376
  • Last updated
    2022-05-25 v2
  • Checksum
    C13A8B5DBCE1554B
MGMNKAELIDVLTQKLGSDRRQATAAVENVVDTIVRAVHKGDSVTITGFGVFEQRRRAARVARNPRTGETVKVKPTSVPAFRPGAQFKAVVSGAQRLPAEGPAVKRGVGASAAKKVAKKAPAKKATKAAKKAATKAPARKAATKAPAKKAATKAPAKKAVKATKSPAKKVTKAVKKTAVKASVRKAATKAPAKKAAAKRPATKAPAKKATARRGRK

Sequence caution

The sequence CCP45791.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias117-134Basic residues
Compositional bias162-179Basic residues
Sequence conflict210in Ref. 1; no nucleotide entry

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AL123456
EMBL· GenBank· DDBJ
CCP45791.1
EMBL· GenBank· DDBJ
Genomic DNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

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