Rv1909c (furA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ferric uptake regulation protein
- REFSEQ: ferric uptake regulation protein furA (fur)
- PATRIC: Transcriptional regulator FUR family
- TUBERCULIST: Ferric uptake regulation protein FurA (fur)
- NCBI: Ferric uptake regulation protein FurA (fur)
- updated information (H37Rv4):
  - gene name: furA
  - function:
  - reference:
Type: Not Target
Start: 2156149
End: 2156592
Operon:

Trans-membrane region:
Role: I.J.1 - Repressors/activators
GO terms:
- GO:0046872 - metal ion binding (Uniprot)
- GO:0010039 - response to iron ion (Uniprot)
- GO:0006979 - response to oxidative stress (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005737 - cytoplasm (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): (none with >35% aa id)
Links to additional information on furA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.905 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VSSIPDYAEQLRTADLRVTRPRVAVLEAVNAHPHADTETIFGAVRFALPDVSRQAVYDVLHALTAAGLVRKIQPSGSVARYESRVGDNHHHIVCRSCGVI
ADVDCAVGEAPCLTASDHNGFLLDEAEVIYWGLCPDCSISDTSRSHP

(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)	1.56 (0.21)	0.9 (0.38)
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

Rv1909c/furA, gene len: 443 bp, num TA sites: 11

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=-1.09)	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=-0.552)	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=1.92)	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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0767c (-) (Direct binding)

Property	Value	Creator	Evidence	PMID	Comment
Citation	Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. AS. Pym, P. Domenech et al. Mol. Microbiol. 2001	kaveri.verma	IMP	11401695	Mutation studies
Interaction	Transcription Rv1908c	kaveri.verma	IMP		Mutation studies AS. Pym, P. Domenech et al. Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis. Mol. Microbiol. 2001
Interaction	Regulatory Rv0117	shahanup86	IEP		Co-expression (Functional linkage) M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv3416	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv2034	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
Interaction	RegulatedBy Rv0117	yamir.moreno	IDA		One hybrid reporter system. Physical binding of the regulator to the regulated promoter proved by using electrophoretic mobility shift assay. . M. Guo, H. Feng et al. Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res. 2009
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 Rv1909c	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 Rv1909c	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

TB Genome Annotation Portal

Rv1909c (furA)

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

TB Genome Annotation Portal

Rv1909c (furA)

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