Rv1461 (-)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: Fe-S cluster assembly protein SufB
- REFSEQ: hypothetical protein
- PATRIC: Iron-sulfur cluster assembly protein SufB @ intein-containing
- TUBERCULIST: Conserved protein
- NCBI: hypothetical protein
- updated information (H37Rv4):
  - gene name: sufB/pps1
  - function: assembly of iron-sulfur clusters
  - reference: (Huet 2005, PMID: 16109955)
Type: Essential
Start: 1646989
End: 1649529
Operon:

Trans-membrane region:
Role: V - Conserved hypotheticals
GO terms:
- GO:0090305 - nucleic acid phosphodiester bond hydrolysis (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016787 - hydrolase activity (Uniprot)
- GO:0016539 - intein-mediated protein splicing (Uniprot)
- GO:0016226 - iron-sulfur cluster assembly (Uniprot)
- GO:0006314 - intron homing (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004519 - endonuclease activity (Uniprot)
- GO:0004518 - nuclease activity (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 Rv1461:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -7.788 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MTLTPEASKSVAQPPTQAPLTQEEAIASLGRYGYGWADSDVAGANAQRGLSEAVVRDISAKKNEPDWMLQSRLKALRIFDRKPIPKWGSNLDGIDFDNIK
YFVRSTEKQAASWDDLPEDIRNTYDRLGIPEAEKQRLVAGVAAQYESEVVYHQIREDLEAQGVIFLDTDTGLREHPDIFKEYFGTVIPAGDNKFSALNTA
VWSGGSFIYVPPGVHVDIPLQAYFRINTENMGQFERTLIIADEGSYVHYVEGCLPAGELITTADGDLRPIESIRVGDFVTGHDGRPHRVTAVQVRDLDGE
LFTFTPMSPANAFSVTAEHPLLAIPRDEVRVMRKERNGWKAEVNSTKLRSAEPRWIAAKDVAEGDFLIYPKPKPIPHRTVLPLEFARLAGYYLAEGHACL
TNGCESLIFSFHSDEFEYVEDVRQACKSLYEKSGSVLIEEHKHSARVTVYTKAGYAAMRDNVGIGSSNKKLSDLLMRQDETFLRELVDAYVNGDGNVTRR
NGAVWKRVHTTSRLWAFQLQSILARLGHYATVELRRPGGPGVIMGRNVVRKDIYQVQWTEGGRGPKQARDCGDYFAVPIKKRAVREAHEPVYNLDVENPD
SYLAYGFAVHNCTAPIYKSDSLHSAVVEIIVKPHARVRYTTIQNWSNNVYNLVTKRARAEAGATMEWIDGNIGSKVTMKYPAVWMTGEHAKGEVLSVAFA
GEDQHQDTGAKMLHLAPNTSSNIVSKSVARGGGRTSYRGLVQVNKGAHGSRSSVKCDALLVDTVSRSDTYPYVDIREDDVTMGHEATVSKVSENQLFYLM
SRGLTEDEAMAMVVRGFVEPIAKELPMEYALELNRLIELQMEGAVG

(Nucleotide sequence available on KEGG)

Additional Information

sufB or pps1 - assembly of iron-sulfur clusters.

Huet G, Daffé M, Saves I. Identification of the Mycobacterium
tuberculosis SUF machinery as the exclusive mycobacterial system of
[Fe-S] cluster assembly: evidence for its implication in the
pathogen's survival. J Bacteriol. 2005 Sep;187(17):6137-46. doi:
10.1128/JB.187.17.6137-6146.2005. PMID: 16109955; PMCID: PMC1196142.

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)	2.5 (0.74)	1.49 (0.77)
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

Rv1461/-, gene len: 2540 bp, num TA sites: 59

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.0)	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

RNA processing and modification

Energy production and conversion

Chromatin structure and dynamics

Amino acid transport and metabolism

Cell cycle control, cell division, chromosome partitioning

Carbohydrate transport and metabolism

Nucleotide transport and metabolism

Lipid transport and metabolism

Coenzyme transport and metabolism

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

Differentially expressed as result of RNASeq in glycerol environment (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

Conditionally essential as result of TNSeq (Only top 20 genes shown sorted by log fold change with p_adj 0.05).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

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

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0967 (csoR) (Direct binding)
- Rv1816 (-) (Direct binding)
- Rv0691c (-) (Upstream of operon)
- Rv1033c (trcR) (Upstream of operon)
- Rv1460 (-) (Upstream of operon)
- Rv2610c (pimA) (Upstream of operon)

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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv1463	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,M. Daff,I. Saves Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. J. Bacteriol. 2005
Interaction	Regulatory Rv1464	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,JP. Castaing,D. Fournier,M. Daff,I. Saves Protein splicing of SufB is crucial for the functionality of the Mycobacterium tuberculosis SUF machinery. J. Bacteriol. 2006
Interaction	PhysicalInteraction Rv1462	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,M. Daff,I. Saves Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. J. Bacteriol. 2005
Interaction	PhysicalInteraction Rv1463	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) B. Murugasu-Oei, A. Tay et al. Upregulation of stress response genes and ABC transporters in anaerobic stationary-phase Mycobacterium smegmatis. Mol. Gen. Genet. 1999
Citation	Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. authors,G. Huet,M. Daff,I. Saves J. Bacteriol. 2005	vijayachitra	IPI	16109955	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv1462	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,M. Daff,I. Saves Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. J. Bacteriol. 2005
Interaction	Regulatory Rv1463	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,M. Daff,I. Saves Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. J. Bacteriol. 2005
Interaction	Regulatory Rv1464	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,M. Daff,I. Saves Identification of the Mycobacterium tuberculosis SUF machinery as the exclusive mycobacterial system of [Fe-S] cluster assembly: evidence for its implication in the pathogen's survival. J. Bacteriol. 2005
Citation	Protein splicing of SufB is crucial for the functionality of the Mycobacterium tuberculosis SUF machinery. authors,G. Huet,JP. Castaing,D. Fournier,M. Daff,I. Saves J. Bacteriol. 2006	vijayachitra	IPI	16621837	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv1462	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,JP. Castaing,D. Fournier,M. Daff,I. Saves Protein splicing of SufB is crucial for the functionality of the Mycobacterium tuberculosis SUF machinery. J. Bacteriol. 2006
Interaction	Regulatory Rv1463	vijayachitra	IPI		Yeast two-hybrid (Physical interaction) authors,G. Huet,JP. Castaing,D. Fournier,M. Daff,I. Saves Protein splicing of SufB is crucial for the functionality of the Mycobacterium tuberculosis SUF machinery. J. Bacteriol. 2006
Interaction	RegulatedBy Rv0348	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv3557c	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 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 Rv1931c	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 Rv1359	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 Rv0818	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 Rv0445c	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 Rv0260c	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

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