Rv3855 (ethR)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: HTH-type transcriptional regulator EthR
- REFSEQ: transcriptional regulatory repressor protein (TETR-family) ETHR
- PATRIC: Transcriptional repressor EthR TetR family
- TUBERCULIST: Transcriptional regulatory repressor protein (TetR-family) EthR
- NCBI: Transcriptional regulatory repressor protein (TetR-family) EthR
- updated information (H37Rv4):
  - gene name: ethR
  - function:
  - reference:
Coordinates in H37Rv: 4327549 - 4328199
Gene length: 651 bp (with stop codon), 216 aa (without stop codon)
Operon:

Trans-membrane region:
Role: I.J.1 - Repressors/activators
GO terms:
- GO:0046677 - response to antibiotic (Uniprot)
- GO:0045892 - negative regulation of transcription, DNA-templated (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0003700 - DNA binding transcription factor activity (Uniprot)
- GO:0003677 - DNA binding (Uniprot)
- GO:0000976 - transcription regulatory region sequence-specific DNA binding (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: 1u9o, 3q0v, 3q0u, 3q3s, 4dw6, 1t56, 3tp0, 3qpl, 3sdg, 3o8g, 3tp3, 1u9n, 3g1o, 3g1l, 3g1m, 3sfi, 3q0w, 3o8h
Search for Latest Homologs in PDB

Top 10 Homologs in PDB (as of Apr 2026):

PDB	aa ident	species	PDB title
5NZ1	100%	Mycobacterium tuberculosis	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with sutezolid
5NZ0	100%	Mycobacterium tuberculosis	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with linezolid
5MYW	100%	Mycobacterium tuberculosis H37Rv	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound SB-435634 at 1.77A resolution
5MYT	100%	Mycobacterium tuberculosis	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK921295A at 1.61A resolution
5MYS	100%	Mycobacterium tuberculosis	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK920684A at 1.59A resolution
5MYR	100%	Mycobacterium tuberculosis	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK735816A at 1.83A resolution
5MYN	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK445886A at 1.56A resolution
5MYM	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK2032710A at 2.28A resolution
5MYL	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK1570606A at 1.72A resolution
5MXV	100%	Mycobacterium tuberculosis H37Rv	Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound GSK1107112A at 1.63A resolution

Links to additional information on ethR:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.035 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTTSAASQASLPRGRRTARPSGDDRELAILATAENLLEDRPLADISVDDLAKGAGISRPTFYFYFPSKEAVLLTLLDRVVNQADMALQTLAENPADTDRE
NMWRTGINVFFETFGSHKAVTRAGQAARATSVEVAELWSTFMQKWIAYTAAVIDAERDRGAAPRTLPAHELATALNLMNERTLFASFAGEQPSVPEARVL
DTLVHIWVTSIYGENR

(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

Rv3855/ethR, gene len: 650 bp, num TA sites: 12

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-0.0)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=-0.898)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.2)	YM rich vs minimal medium	resampling

Analysis of Positive Selection in Clinical Isolates new

data from Culviner et al (2025) (55,259 Mtb clinical isolates)
- overall pN/pS for Rv3855: 0.710808754
- lineage-specific pN/pS in L1: 0.60334124
- lineage-specific pN/pS in L2: 0.89299083
- lineage-specific pN/pS in L3: 0.778504826
- lineage-specific pN/pS in L4: 0.67805259

Analysis of dN/dS (omega) in a global collection of 10k Mtb clinical isolates using GenomegaMap (Window model)
clinical isolates collection: global set of 10,626 Mtb genomes
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	global set of 10,626 Mtb clinical isolates
under significant positive selection?	NO
omega peak height (95%CI lower bound)	1.4 (0.81)
codons under selection
omega plots
genetic variants*	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

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: see table of TFOE interactions below

Interactions based on ChIPSeq data

Binds To:
Bound By:

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

Binds To:
- Rv0456A (mazF1) (Direct binding)
- Rv1116 (-) (Direct binding)
- Rv1256c (cyp130) (Direct binding)
- Rv1572c (-) (Direct binding)
- Rv1573 (-) (Direct binding)
- Rv1665 (pks11) (Direct binding)
- Rv1963c (mce3R) (Direct binding)
- Rv1986 (-) (Direct binding)
- Rv2107 (PE22) (Direct binding)
- Rv2145c (wag31) (Direct binding)
- Rv2307B (-) (Direct binding)
- Rv2452c (-) (Direct binding)
- Rv2547 (vapB19) (Direct binding)
- Rv2779c (-) (Direct binding)
- Rv2780 (ald) (Direct binding)
- Rv3269 (-) (Direct binding)
- Rv3290c (lat) (Direct binding)
- Rv3746c (PE34) (Direct binding)
- Rv3747 (-) (Direct binding)
- Rv3854c (ethA) (Direct binding)
- Rv3855 (ethR) (Direct binding)
- Rv1255c (-) (Upstream of operon)
- Rv2778c (-) (Upstream of operon)
- Rv3270 (ctpC) (Upstream of operon)
- Rv3288c (usfY) (Upstream of operon)
- Rv3289c (-) (Upstream of operon)
Bound By:
- Rv2250c (-) (Direct binding)
- Rv3249c (-) (Direct binding)
- Rv3855 (ethR) (Direct binding)

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

TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01

gene	dysregulated by OE of	LFC
Rv3855/ethR	Rv3855/ethR	3.28
Rv3855/ethR	Rv0818/glnR	1.17
Rv3855/ethR	Rv0238/fdmR	-1.03
Rv3855/ethR	Rv3223c/sigH	-1.18
Rv3855/ethR	Rv3058c/-	-1.22

Upregulates:
- Rv0394c (-)
- Rv3855 (ethR)
Upregulated by:
- Rv0818 (-)
- Rv3855 (ethR)
Downregulates:
- Rv3854c (ethA)
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Citation	Activation of the pro-drug ethionamide is regulated in mycobacteria. AR. Baulard, JC. Betts et al. J. Biol. Chem. 2000	priti.priety	IEP	10869356	Co-expression (Functional linkage)
Interaction	Regulatory Rv3854c	priti.priety	IEP		Co-expression (Functional linkage) AR. Baulard, JC. Betts et al. Activation of the pro-drug ethionamide is regulated in mycobacteria. J. Biol. Chem. 2000
Citation	Activation of the pro-drug ethionamide is regulated in mycobacteria. AR. Baulard, JC. Betts et al. J. Biol. Chem. 2000	ashwinigbhat	IEP	10869356	Co-expression (Functional linkage)
Interaction	Regulatory Rv3854c	ashwinigbhat	IEP		Co-expression (Functional linkage) AR. Baulard, JC. Betts et al. Activation of the pro-drug ethionamide is regulated in mycobacteria. J. Biol. Chem. 2000
Interaction	Regulates Rv3854c	yamir.moreno	TAS		Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Citation	The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. G. Balzsi, AP. Heath et al. Mol. Syst. Biol. 2008	yamir.moreno	TAS	18985025	Literature previously reported link (from Balazsi et al. 2008). Traceable author statement to experimental support.

TB Genome Annotation Portal