P9WMK7 · DBH_MYCTU
- ProteinDNA-binding protein HupB
- GenehupB
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids216 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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).
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).
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.
Catalytic activity
- 4 Fe2+ + 4 H+ + O2 = 4 Fe3+ + 2 H2OThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.252 mM | Fe2+ |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular region | |
Cellular Component | nucleoid | |
Cellular Component | peptidoglycan-based cell wall | |
Cellular Component | plasma membrane | |
Cellular Component | protein-DNA complex | |
Molecular Function | damaged DNA binding | |
Molecular Function | DNA binding | |
Molecular Function | DNA-binding transcription activator activity | |
Molecular Function | double-stranded DNA binding | |
Molecular Function | ferric iron binding | |
Molecular Function | ferroxidase activity | |
Molecular Function | structural constituent of chromatin | |
Molecular Function | supercoiled DNA binding | |
Molecular Function | transcription cis-regulatory region binding | |
Biological Process | biofilm matrix assembly | |
Biological Process | cell wall organization | |
Biological Process | cellular response to iron ion starvation | |
Biological Process | chromosome condensation | |
Biological Process | DNA protection | |
Biological Process | iron ion transport | |
Biological Process | nucleoid organization | |
Biological Process | positive regulation of DNA-templated transcription |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA-binding protein HupB
- EC number
- Short namesHupB
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Strains
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium tuberculosis complex
Accessions
- Primary accessionP9WMK7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 140 | Significantly decreased trimethylation of HupB by host SUV39H1, increased bacterial survival in human macrophages, SUV39H1 no longer inhibits biofilm formation. | ||||
Sequence: K → A | ||||||
Mutagenesis | 185 | No change in trimethylation by human SUV39H1. | ||||
Sequence: K → A | ||||||
Mutagenesis | 216 | No change in trimethylation by human SUV39H1. | ||||
Sequence: K → A |
PTM/Processing
Features
Showing features for initiator methionine, propeptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Propeptide | PRO_0000455388 | 2 | Removed; alternate | |||
Sequence: G | ||||||
Chain | PRO_0000104950 | 2-216 | DNA-binding protein HupB | |||
Sequence: GMNKAELIDVLTQKLGSDRRQATAAVENVVDTIVRAVHKGDSVTITGFGVFEQRRRAARVARNPRTGETVKVKPTSVPAFRPGAQFKAVVSGAQRLPAEGPAVKRGVGASAAKKVAKKAPAKKATKAAKKAATKAPARKAATKAPAKKAATKAPAKKAVKATKSPAKKVTKAVKKTAVKASVRKAATKAPAKKAAAKRPATKAPAKKATARRGRK | ||||||
Modified residue | 3 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000455389 | 3-216 | DNA-binding protein HupB, propeptide removed | |||
Sequence: MNKAELIDVLTQKLGSDRRQATAAVENVVDTIVRAVHKGDSVTITGFGVFEQRRRAARVARNPRTGETVKVKPTSVPAFRPGAQFKAVVSGAQRLPAEGPAVKRGVGASAAKKVAKKAPAKKATKAAKKAATKAPARKAATKAPAKKAATKAPAKKAVKATKSPAKKVTKAVKKTAVKASVRKAATKAPAKKAAAKRPATKAPAKKATARRGRK | ||||||
Modified residue | 5 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 74 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 88 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 105 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 118 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 135 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 140 | N6,N6,N6-trimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 148 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 169 | N6-acetyllysine | ||||
Sequence: K |
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).
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
- PTM
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).
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
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 3-92 | Bacterial histone-like domain | ||||
Sequence: MNKAELIDVLTQKLGSDRRQATAAVENVVDTIVRAVHKGDSVTITGFGVFEQRRRAARVARNPRTGETVKVKPTSVPAFRPGAQFKAVVS | ||||||
Region | 102-216 | Disordered | ||||
Sequence: PAVKRGVGASAAKKVAKKAPAKKATKAAKKAATKAPARKAATKAPAKKAATKAPAKKAVKATKSPAKKVTKAVKKTAVKASVRKAATKAPAKKAAAKRPATKAPAKKATARRGRK | ||||||
Region | 103-216 | Degenerate repeats region | ||||
Sequence: AVKRGVGASAAKKVAKKAPAKKATKAAKKAATKAPARKAATKAPAKKAATKAPAKKAVKATKSPAKKVTKAVKKTAVKASVRKAATKAPAKKAAAKRPATKAPAKKATARRGRK | ||||||
Compositional bias | 117-134 | Basic residues | ||||
Sequence: AKKAPAKKATKAAKKAAT | ||||||
Compositional bias | 162-179 | Basic residues | ||||
Sequence: ATKSPAKKVTKAVKKTAV |
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).
Residues 1-102 stimulate Top1 and physically interact with it (By similarity).
Sequence similarities
Belongs to the bacterial histone-like protein family. Long actinobacterial subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length216
- Mass (Da)22,376
- Last updated2022-05-25 v2
- ChecksumC13A8B5DBCE1554B
Sequence caution
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 117-134 | Basic residues | ||||
Sequence: AKKAPAKKATKAAKKAAT | ||||||
Compositional bias | 162-179 | Basic residues | ||||
Sequence: ATKSPAKKVTKAVKKTAV | ||||||
Sequence conflict | 210 | in Ref. 1; no nucleotide entry | ||||
Sequence: T → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL123456 EMBL· GenBank· DDBJ | CCP45791.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation |