Rv2358 (smtB)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ArsR family transcriptional regulator
- REFSEQ: ArsR family transcriptional regulator
- PATRIC: Transcriptional regulator ArsR family
- TUBERCULIST: Probable transcriptional regulatory protein SmtB (probably ArsR-family)
- NCBI: Probable transcriptional regulatory protein SmtB (probably ArsR-family)
- updated information (H37Rv4):
  - gene name: smtB
  - function: zinc-responsive transcription factor
  - reference:
Type: Not Target
Start: 2641246
End: 2641653
Operon:

Trans-membrane region:
Role: I.J.1 - Repressors/activators
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0044212 - transcription regulatory region DNA binding (Uniprot)
- GO:0010043 - response to zinc ion (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0003700 - DNA binding transcription factor activity (Uniprot)
- GO:0003677 - 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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2LKP	39%	Mycobacterium tuberculosis	solution structure of apo-NmtR
2JSC	37%	Mycobacterium tuberculosis	NMR structure of the cadmium metal-sensor CMTR from Mycobacterium tuberculosis
6J0E	36%	Corynebacterium glutamicum ATCC 13032	Structures of two ArsR As(III)-responsive repressors: implications for the mechanism of derepression

Links to additional information on smtB:
- KEGG - nucleotide and amino acid sequences of gene
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -3.238 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MVTSPSTPTAAHEDVGADEVGGHQHPADRFAECPTFPAPPPREILDAAGELLRALAAPVRIAIVLQLRESQRCVHELVDALHVPQPLVSQHLKILKAAGV
VTGERSGREVLYRLADHHLAHIVLDAVAHAGEDAI

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
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.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	0.92 (0.18)	1.9 (0.57)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

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

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv2358/smtB, gene len: 407 bp, num TA sites: 5

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	non-essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	uncertain	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=-2.24)	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=-0.601)	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, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.77)	YM rich vs minimal medium	resampling

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:
- No bindings to other targets were found.
Bound By:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Direct binding)
- Rv2250c (-) (Direct binding)
- Rv2324 (-) (Direct binding)

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

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

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2358 (smtB)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Transcription Rv2359	jhum4u2006	IPI		Affinity purification (Physical interaction) F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Citation	Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005	jhum4u2006	IPI	16077132	Affinity purification (Physical interaction)
Interaction	Transcription Rv2359	jhum4u2006	IPI		Affinity purification (Physical interaction) F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Interaction	Transcription Rv2358	jhum4u2006	IPI		Affinity purification (Physical interaction) F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Interaction	Transcription Rv2358	jhum4u2006	IPI		Affinity purification (Physical interaction) F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Interaction	Regulates Rv2359	yamir.moreno	IDA		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Citation	Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005	yamir.moreno	IEP	16077132	Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.).
Interaction	Regulates Rv2359	yamir.moreno	IEP		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Citation	Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005	yamir.moreno	IDA	16077132	Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.).
Interaction	Regulates Rv2358	yamir.moreno	IDA		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Interaction	RegulatedBy Rv2358	yamir.moreno	IDA		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Citation	Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005	yamir.moreno	IEP	16077132	Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.).
Interaction	Regulates Rv2358	yamir.moreno	IEP		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Interaction	RegulatedBy Rv2358	yamir.moreno	IEP		Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.). F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005
Citation	Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005	yamir.moreno	IDA	16077132	Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.).
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.
Interaction	Regulates Rv2358	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
Interaction	RegulatedBy Rv2358	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.
Interaction	Regulates Rv2359	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

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Transcription Rv2359

jhum4u2006

IPI

Affinity purification (Physical interaction)
F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005

Citation

Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005

jhum4u2006

IPI

16077132

Affinity purification (Physical interaction)

Interaction

Transcription Rv2359

jhum4u2006

IPI

Affinity purification (Physical interaction)
F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005

Interaction

Transcription Rv2358

jhum4u2006

IPI

Affinity purification (Physical interaction)
F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005

Interaction

Transcription Rv2358

jhum4u2006

IPI

Affinity purification (Physical interaction)
F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005

Interaction

Regulates Rv2359

yamir.moreno

IDA

Electrophoretic mobility shift assays EMSA. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . LacZ-promoter fusion. expression levels of LacZ- regulated promoter fusion measured and compared between wild-type and trans-element mutation (knockout, over expression etc.).
F. Canneva, M. Branzoni et al. Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. J. Bacteriol. 2005

Citation

Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005

yamir.moreno

IEP

16077132

Interaction

Regulates Rv2359

yamir.moreno

IEP

Citation

Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005

yamir.moreno

IDA

16077132

Interaction

Regulates Rv2358

yamir.moreno

IDA

Interaction

RegulatedBy Rv2358

yamir.moreno

IDA

Citation

Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005

yamir.moreno

IEP

16077132

Interaction

Regulates Rv2358

yamir.moreno

IEP

Interaction

RegulatedBy Rv2358

yamir.moreno

IEP

Citation

Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc. F. Canneva, M. Branzoni et al. J. Bacteriol. 2005

yamir.moreno

IDA

16077132

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.

Interaction

Regulates Rv2358

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

Interaction

RegulatedBy Rv2358

yamir.moreno

TAS

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.

Interaction

Regulates Rv2359

yamir.moreno

TAS

Comments

TB Genome Annotation Portal

Rv2358 (smtB)

Amino Acid Sequence

Additional Information

Analysis of Positive Selection in Clinical Isolates *new*

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

Interactions based on ChIPSeq data

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

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

TBCAP

Comments

Analysis of Positive Selection in Clinical Isolates new