Rv3246c (mtrA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: DNA-binding response regulator mtrA
- REFSEQ: two component sensory transduction transcriptional regulatory protein MTRA
- PATRIC: DNA-binding response regulator mtrA
- TUBERCULIST: Two component sensory transduction transcriptional regulatory protein MtrA
- NCBI: Two component sensory transduction transcriptional regulatory protein MtrA
- updated information (H37Rv4):
  - gene name: mtrA
  - function:
  - reference:
Type: Not Target
Start: 3626663
End: 3627349
Operon:

Trans-membrane region:
Role: I.J.2 - Two component systems
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0045893 - positive regulation of transcription, DNA-templated (Uniprot)
- GO:0044117 - growth of symbiont in host (Uniprot)
- GO:0006468 - protein phosphorylation (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0003677 - DNA binding (Uniprot)
- GO:0000160 - phosphorelay signal transduction system (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 2gwr, 3nhz
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
3NHZ	100%	Mycobacterium tuberculosis	Structure of N-terminal Domain of MtrA
2GWR	100%	Mycobacterium tuberculosis	Crystal structure of the response regulator protein mtrA from Mycobacterium Tuberculosis
3F6P	52%	Bacillus subtilis	Crystal Structure of unphosphorelated receiver domain of YycF
2ZWM	52%	Bacillus subtilis	Crystal structure of YycF receiver domain from Bacillus subtilis
4UHS	51%	ESCHERICHIA COLI	Crystal structure of the receiver domain of CpxR from E. coli (tetragonal form)
4UHK	51%	ESCHERICHIA COLI	Crystal structure of the receiver domain of CpxR from E. coli (phosphorylated)
4UHJ	51%	ESCHERICHIA COLI	Crystal structure of the receiver domain of CpxR from E. coli (orthorhombic form)
2IYN	50%	ESCHERICHIA COLI	The co-factor-induced pre-active conformation in PhoB
1ZES	50%	Escherichia coli	BeF3- activated PhoB receiver domain
1B00	50%	Escherichia coli	PHOB RECEIVER DOMAIN FROM ESCHERICHIA COLI

Links to additional information on mtrA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -5.325 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MDTMRQRILVVDDDASLAEMLTIVLRGEGFDTAVIGDGTQALTAVRELRPDLVLLDLMLPGMNGIDVCRVLRADSGVPIVMLTAKTDTVDVVLGLESGAD
DYIMKPFKPKELVARVRARLRRNDDEPAEMLSIADVEIDVPAHKVTRNGEQISLTPLEFDLLVALARKPRQVFTRDVLLEQVWGYRHPADTRLVNVHVQR
LRAKVEKDPENPTVVLTVRGVGYKAGPP

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.995550; 11 non-insertions in a row out of 11 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999600; 11 non-insertions in a row out of 11 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.999850; 11 non-insertions in a row out of 11 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999800; 11 non-insertions in a row out of 11 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999350; 11 non-insertions in a row out of 11 sites
No-Data	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Too-Short	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: -1
Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

Binds To:
Bound By:

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- Rv0040c (mtc28) (Direct binding)
- Rv0041 (leuS) (Direct binding)
- Rv0113 (gmhA) (Direct binding)
- Rv0116c (ldtA) (Direct binding)
- Rv0129c (fbpC) (Direct binding)
- Rv0130 (htdZ) (Direct binding)
- Rv0179c (lprO) (Direct binding)
- Rv0188 (-) (Direct binding)
- Rv0208c (-) (Direct binding)
- Rv0209 (-) (Direct binding)
- Rv0252 (nirB) (Direct binding)
- Rv0309 (-) (Direct binding)
- Rv0320 (-) (Direct binding)
- Rv0456A (mazF1) (Direct binding)
- Rv0469 (umaA) (Direct binding)
- Rv0643c (mmaA3) (Direct binding)
- Rv0653c (-) (Direct binding)
- Rv0654 (-) (Direct binding)
- Rv0822c (-) (Direct binding)
- Rv0950c (-) (Direct binding)
- Rv0996 (-) (Direct binding)
- Rv1004c (-) (Direct binding)
- Rv1009 (rpfB) (Direct binding)
- Rv1089A (celA2a) (Direct binding)
- Rv1116 (-) (Direct binding)
- Rv1158c (-) (Direct binding)
- Rv1159 (pimE) (Direct binding)
- Rv1169c (lipX) (Direct binding)
- Rv1170 (mshB) (Direct binding)
- Rv1268c (-) (Direct binding)
- Rv1433 (-) (Direct binding)
- Rv1469 (ctpD) (Direct binding)
- Rv1477 (ripA) (Direct binding)
- Rv1522c (mmpL12) (Direct binding)
- Rv1523 (-) (Direct binding)
- Rv1690 (lprJ) (Direct binding)
- Rv1754c (-) (Direct binding)
- Rv1772 (-) (Direct binding)
- Rv1791 (PE19) (Direct binding)
- Rv1815 (-) (Direct binding)
- Rv1883c (-) (Direct binding)
- Rv1884c (rpfC) (Direct binding)
- Rv1886c (fbpB) (Direct binding)
- Rv1908c (katG) (Direct binding)
- Rv1918c (PPE35) (Direct binding)
- Rv1987 (-) (Direct binding)
- Rv2162c (PE_PGRS38) (Direct binding)
- Rv2243 (fabD) (Direct binding)
- Rv2293c (-) (Direct binding)
- Rv2352c (PPE38) (Direct binding)
- Rv2462c (tig) (Direct binding)
- Rv2463 (lipP) (Direct binding)
- Rv2525c (-) (Direct binding)
- Rv2722 (-) (Direct binding)
- Rv2723 (-) (Direct binding)
- Rv2758c (vapB21) (Direct binding)
- Rv2864c (-) (Direct binding)
- Rv2884 (-) (Direct binding)
- Rv3159c (PPE53) (Direct binding)
- Rv3171c (hpx) (Direct binding)
- Rv3241c (-) (Direct binding)
- Rv3245c (mtrB) (Direct binding)
- Rv3246c (mtrA) (Direct binding)
- Rv3276c (purK) (Direct binding)
- Rv3277 (-) (Direct binding)
- Rv3354 (-) (Direct binding)
- Rv3532 (PPE61) (Direct binding)
- Rv3583c (-) (Direct binding)
- Rv3645 (-) (Direct binding)
- Rv3674c (nth) (Direct binding)
- Rv3675 (-) (Direct binding)
- Rv3676 (crp) (Direct binding)
- Rv3681c (whiB4) (Direct binding)
- Rv3716c (-) (Direct binding)
- Rv3717 (-) (Direct binding)
- Rv3810 (pirG) (Direct binding)
- Rv0114 (gmhB) (Upstream of operon)
- Rv0115 (hddA) (Upstream of operon)
- Rv0207c (-) (Upstream of operon)
- Rv0210 (-) (Upstream of operon)
- Rv0253 (nirD) (Upstream of operon)
- Rv0321 (dcd) (Upstream of operon)
- Rv0655 (mkl) (Upstream of operon)
- Rv1010 (ksgA) (Upstream of operon)
- Rv1090 (celA2b) (Upstream of operon)
- Rv1157c (-) (Upstream of operon)
- Rv1168c (PPE17) (Upstream of operon)
- Rv1434 (-) (Upstream of operon)
- Rv1478 (-) (Upstream of operon)
- Rv1524 (-) (Upstream of operon)
- Rv1691 (-) (Upstream of operon)
- Rv1692 (-) (Upstream of operon)
- Rv1693 (-) (Upstream of operon)
- Rv1694 (tlyA) (Upstream of operon)
- Rv1695 (ppnK) (Upstream of operon)
- Rv1696 (recN) (Upstream of operon)
- Rv1882c (-) (Upstream of operon)
- Rv1885c (-) (Upstream of operon)
- Rv2292c (-) (Upstream of operon)
- Rv3244c (lpqB) (Upstream of operon)
- Rv3274c (fadE25) (Upstream of operon)
- Rv3275c (purE) (Upstream of operon)
- Rv3581c (ispF) (Upstream of operon)
- Rv3582c (ispD) (Upstream of operon)
- Rv3673c (-) (Upstream of operon)
- Rv3715c (recR) (Upstream of operon)
Bound By:
- Rv1353c (-) (Direct binding)
- Rv2324 (-) (Direct binding)
- Rv3246c (mtrA) (Direct binding)
- Rv3830c (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. R. Sun, PJ. Converse et al. Mol. Microbiol. 2004	sourish10	IEP	15049808	Co-expression (Functional linkage)
Interaction	Signaling Rv2069	sourish10	IEP		Co-expression (Functional linkage) R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004
Interaction	Signaling Rv3245c	sourish10	IPI		Co-expression (Functional linkage) TC. Zahrt & V. Deretic An essential two-component signal transduction system in Mycobacterium tuberculosis. J. Bacteriol. 2000
Interaction	Signaling Rv3245c	sourish10	IPI		Co-expression (Functional linkage) KK. Singh, X. Zhang et al. Antigens of Mycobacterium tuberculosis expressed during preclinical tuberculosis: serological immunodominance of proteins with repetitive amino acid sequences. Infect. Immun. 2001
Citation	The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. authors,GA. Cangelosi,JS. Do,R. Freeman,JG. Bennett,M. Semret,MA. Behr Antimicrob. Agents Chemother. 2006	sourish10	TAS	16436697	Co-expression (Functional linkage)
Interaction	Signaling Rv3245c	sourish10	TAS		Co-expression (Functional linkage) authors,GA. Cangelosi,JS. Do,R. Freeman,JG. Bennett,M. Semret,MA. Behr The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob. Agents Chemother. 2006
Citation	An essential two-component signal transduction system in Mycobacterium tuberculosis. TC. Zahrt & V. Deretic J. Bacteriol. 2000	sourish10	TAS	10851001	Co-expression (Functional linkage)
Interaction	Signaling Rv3245c	sourish10	TAS		Co-expression (Functional linkage) TC. Zahrt & V. Deretic An essential two-component signal transduction system in Mycobacterium tuberculosis. J. Bacteriol. 2000
Citation	Antigens of Mycobacterium tuberculosis expressed during preclinical tuberculosis: serological immunodominance of proteins with repetitive amino acid sequences. KK. Singh, X. Zhang et al. Infect. Immun. 2001	sourish10	TAS	11349098	Co-expression (Functional linkage)
Interaction	Signaling Rv3245c	sourish10	TAS		Co-expression (Functional linkage) KK. Singh, X. Zhang et al. Antigens of Mycobacterium tuberculosis expressed during preclinical tuberculosis: serological immunodominance of proteins with repetitive amino acid sequences. Infect. Immun. 2001
Interaction	Regulatory Rv3244c	harsharohiratruefriend	IMP		Co-expression (Functional linkage) N. Mker, M. Brocker et al. Deletion of the genes encoding the MtrA-MtrB two-component system of Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics susceptibility and expression of genes involved in osmoprotection. Mol. Microbiol. 2004
Interaction	Regulatory Rv3244c	harsharohiratruefriend	IMP		Co-expression (Functional linkage) authors,PA. Hoskisson,MI. Hutchings MtrAB-LpqB: a conserved three-component system in actinobacteria? Trends Microbiol. 2006
Interaction	Signaling Rv3245c	sourish10	IPI		Co-expression (Functional linkage) authors,GA. Cangelosi,JS. Do,R. Freeman,JG. Bennett,M. Semret,MA. Behr The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob. Agents Chemother. 2006
Interaction	Regulatory Rv2069	priti.priety	IEP		Co-expression (Functional linkage) R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004
Interaction	Regulatory Rv2069	ashwinigbhat	IEP		Co-expression (Functional linkage) R. Sun, PJ. Converse et al. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol. Microbiol. 2004

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