Rv2703 (sigA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: RNA polymerase sigma factor rpoD
- REFSEQ: RNA polymerase sigma factor
- PATRIC: RNA polymerase sigma factor RpoD
- TUBERCULIST: RNA polymerase sigma factor SigA (sigma-A)
- NCBI: RNA polymerase sigma factor SigA (sigma-A)
- updated information (H37Rv4):
  - gene name: sigA
  - function:
  - reference:
Type: Not Target
Start: 3017835
End: 3019421
Operon:

Trans-membrane region:
Role: II.A.7 - RNA synthesis, RNA modification and DNA transcription
GO terms:
- GO:2000142 - regulation of DNA-templated transcription, initiation (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016987 - bacterial sigma factor activity (Uniprot)
- GO:0009415 - response to water (Uniprot)
- GO:0009405 - pathogenesis (Uniprot)
- GO:0006355 - regulation of transcription, DNA-templated (Uniprot)
- GO:0006352 - DNA-templated transcription, initiation (Uniprot)
- GO:0006351 - transcription, DNA-templated (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005515 - protein binding (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
4X8K	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RbpA-SID in complex with SigmaA domain 2
6VW0	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP S456L mutant open promoter complex
6VVZ	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP S456L mutant transcription initiation intermediate structure with Sorangicin
6VVY	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis WT RNAP transcription open promoter complex with Sorangicin
6VVX	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis WT RNAP transcription initiation intermediate structure with Sorangicin
6M7J	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP with RbpA/us fork and Corallopyronin
6FBV	99%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Single particle cryo em structure of Mycobacterium tuberculosis RNA polymerase in complex with Fidaxomicin
6EEC	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP promoter unwinding intermediate complex with RbpA/CarD and AP3 promoter captured by Corallopyronin
6EE8	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP promoter unwinding intermediate complex with RbpA/CarD and AP3 promoter
6EDT	99%	Mycobacterium tuberculosis	Mycobacterium tuberculosis RNAP open promoter complex with RbpA/CarD and AP3 promoter

Links to additional information on sigA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -11.217 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VAATKASTATDEPVKRTATKSPAASASGAKTGAKRTAAKSASGSPPAKRATKPAARSVKPASAPQDTTTSTIPKRKTRAAAKSAAAKAPSARGHATKPRA
PKDAQHEAATDPEDALDSVEELDAEPDLDVEPGEDLDLDAADLNLDDLEDDVAPDADDDLDSGDDEDHEDLEAEAAVAPGQTADDDEEIAEPTEKDKASG
DFVWDEDESEALRQARKDAELTASADSVRAYLKQIGKVALLNAEEEVELAKRIEAGLYATQLMTELSERGEKLPAAQRRDMMWICRDGDRAKNHLLEANL
RLVVSLAKRYTGRGMAFLDLIQEGNLGLIRAVEKFDYTKGYKFSTYATWWIRQAITRAMADQARTIRIPVHMVEVINKLGRIQRELLQDLGREPTPEELA
KEMDITPEKVLEIQQYAREPISLDQTIGDEGDSQLGDFIEDSEAVVAVDAVSFTLLQDQLQSVLDTLSEREAGVVRLRFGLTDGQPRTLDEIGQVYGVTR
ERIRQIESKTMSKLRHPSRSQVLRDYLD

(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: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 21 non-insertions in a row out of 21 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.09
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

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)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Direct binding)
- Rv2034 (-) (Direct binding)
- Rv3488 (-) (Direct binding)

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

Upregulates:
Upregulated by:
- Not upregulated by other genes.
Downregulates:
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv3416	chirupolo	IPI		Affinity purification (Physical interaction) B. Hutter & T. Dick Molecular genetic characterisation of whiB3, a mycobacterial homologue of a Streptomyces sporulation factor. Res. Microbiol. 1999
Interaction	Regulatory Rv3416	chirupolo	IPI		Affinity purification (Physical interaction) AJ. Steyn, DM. Collins et al. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc. Natl. Acad. Sci. U.S.A. 2002
Interaction	Regulatory Rv3416	chirupolo	IPI		Yeast two-hybrid (Physical interaction) B. Hutter & T. Dick Molecular genetic characterisation of whiB3, a mycobacterial homologue of a Streptomyces sporulation factor. Res. Microbiol. 1999
Interaction	Regulatory Rv3416	chirupolo	IPI		Yeast two-hybrid (Physical interaction) AJ. Steyn, DM. Collins et al. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc. Natl. Acad. Sci. U.S.A. 2002
Citation	sigA is an essential gene in Mycobacterium smegmatis. authors,M. Gomez,L. Doukhan,G. Nair,I. Smith Mol. Microbiol. 1998	priyadarshinipriyanka2001	IPI	9720877	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv3416	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) authors,M. Gomez,L. Doukhan,G. Nair,I. Smith sigA is an essential gene in Mycobacterium smegmatis. Mol. Microbiol. 1998
Citation	Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. AJ. Steyn, DM. Collins et al. Proc. Natl. Acad. Sci. U.S.A. 2002	priyadarshinipriyanka2001	IPI	11880648	Yeast two-hybrid (Physical interaction)
Interaction	Regulatory Rv3416	priyadarshinipriyanka2001	IPI		Yeast two-hybrid (Physical interaction) AJ. Steyn, DM. Collins et al. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc. Natl. Acad. Sci. U.S.A. 2002
Interaction	Regulatory Rv2416c	hibeeluck	IEP		co expression(functional linkage) S. Wu, PF. Barnes et al. Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology (Reading, Engl.) 2009
Interaction	Regulatory Rv2416c	hibeeluck	IEP		co expression(functional linkage) MA. Zaunbrecher, RD. Sikes et al. Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2009
Interaction	PhysicalInteraction Rv0667	prabhakarsmail	TAS		Kinetic Assays LP. Miller, JT. Crawford et al. The rpoB gene of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 1994
Interaction	PhysicalInteraction Rv0668	prabhakarsmail	TAS		Kinetic Assays LP. Miller, JT. Crawford et al. The rpoB gene of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 1994
Interaction	Transcription Rv0185	aparna.vchalam	IEP		Co-expression (Functional linkage) S. Wu, PF. Barnes et al. Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology (Reading, Engl.) 2009
Interaction	Transcription Rv0184	aparna.vchalam	IEP		Co-expression (Functional linkage) S. Wu, PF. Barnes et al. Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology (Reading, Engl.) 2009
Interaction	Transcription Rv0181c	aparna.vchalam	IEP		Co-expression (Functional linkage) S. Wu, PF. Barnes et al. Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology (Reading, Engl.) 2009
Interaction	RegulatedBy Rv3223c	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. 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 Rv2720	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. 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 Rv2720	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006

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