Rv2178c (aroG)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 3-deoxy-7-phosphoheptulonate synthase
- REFSEQ: 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroG
- PATRIC: 2-keto-3-deoxy-D-arabino-heptulosonate-7-phosphate synthase II (EC 2.5.1.54)
- TUBERCULIST: 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroG (DAHP synthetase phenylalanine-repressible)
- NCBI: 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroG (DAHP synthetase, phenylalanine-repressible)
- updated information (H37Rv4):
  - gene name: aroG
  - function:
  - reference:
Type: Not Target
Start: 2440332
End: 2441720
Operon:

Trans-membrane region:
Role: I.D.4 - Aromatic amino acid family
GO terms:
- GO:0051260 - protein homooligomerization (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0030145 - manganese ion binding (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009423 - chorismate biosynthetic process (Uniprot)
- GO:0009073 - aromatic amino acid family biosynthetic process (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0003849 - 3-deoxy-7-phosphoheptulonate synthase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- PEP[c] + E4P[c] -> PI[c] + 3DDAH7P[c]
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: 2ypo, 2w1a, 3kgf, 3nud, 2w19, 2b7o, 3rzi, 3nue, 3nv8, 2ypp, 2ypq, 3pfp, 2w1a, 2b7o, 3nud
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
5EX4	100%	Mycobacterium tuberculosis	3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis complexed with tryptophan in all three allosteric binding sites
5E7Z	100%	Mycobacterium tuberculosis	3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with D/L-tryptophan and D-phenylalanine
5E5G	100%	Mycobacterium tuberculosis	3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with D-tryptophan bound in the tryptophan and phenylalanine binding sites
5E4N	100%	Mycobacterium tuberculosis	3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis with D-tyrosine bound in the tyrosine and phenylalanine binding sites
5E40	100%	Mycobacterium tuberculosis	3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis with D-tyrosine bound in the phenylalanine binding site
5E2L	100%	Mycobacterium tuberculosis	3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with D-phenylalanine
5CKX	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Non-covalent complex of DAHP synthase and chorismate mutase from Mycobacterium tuberculosis with bound transition state analog and feedback effectors tyrosine and phenylalanine
5CKV	100%	Mycobacterium tuberculosis	DAHP synthase from Mycobacterium tuberculosis, fully inhibited by tyrosine, phenylalanine, and tryptophan
3RZI	100%	Mycobacterium tuberculosis	The structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from mycobacterium tuberculosis cocrystallized and complexed with phenylalanine and tryptophan
3PFP	100%	Mycobacterium tuberculosis	Structure of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis in complex with an active site inhibitor

Links to additional information on aroG:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -13.367 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MNWTVDIPIDQLPSLPPLPTDLRTRLDAALAKPAAQQPTWPADQALAMRTVLESVPPVTVPSEIVRLQEQLAQVAKGEAFLLQGGDCAETFMDNTEPHIR
GNVRALLQMAVVLTYGASMPVVKVARIAGQYAKPRSADIDALGLRSYRGDMINGFAPDAAAREHDPSRLVRAYANASAAMNLVRALTSSGLASLHLVHDW
NREFVRTSPAGARYEALATEIDRGLRFMSACGVADRNLQTAEIYASHEALVLDYERAMLRLSDGDDGEPQLFDLSAHTVWIGERTRQIDGAHIAFAQVIA
NPVGVKLGPNMTPELAVEYVERLDPHNKPGRLTLVSRMGNHKVRDLLPPIVEKVQATGHQVIWQCDPMHGNTHESSTGFKTRHFDRIVDEVQGFFEVHRA
LGTHPGGIHVEITGENVTECLGGAQDISETDLAGRYETACDPRLNTQQSLELAFLVAEMLRD

(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)	1.79 (0.37)	1.17 (0.32)
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

Rv2178c/aroG, gene len: 1388 bp, num TA sites: 17

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0324 (-)

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

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

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:
- Rv0324 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv0948c	gyanaranjan83	IDA		Spectrophotometric Assay M. Okvist, S. Sasso et al. A novel noncovalent complex of chorismate mutase and DAHP synthase from Mycobacterium tuberculosis: protein purification, crystallization and X-ray diffraction analysis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009
Interaction	PhysicalInteraction Rv0948c	gyanaranjan83	IDA		Structural Analysis M. Okvist, S. Sasso et al. A novel noncovalent complex of chorismate mutase and DAHP synthase from Mycobacterium tuberculosis: protein purification, crystallization and X-ray diffraction analysis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2009
Interaction	RegulatedBy Rv2710	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.. JH. Lee, PC. Karakousis et al. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J. Bacteriol. 2008
Interaction	RegulatedBy Rv0757	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.. SB. Walters, E. Dubnau et al. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006
Interaction	RegulatedBy Rv1395	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 Rv3286c	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.. EP. Williams, JH. Lee et al. Mycobacterium tuberculosis SigF regulates genes encoding cell wall-associated proteins and directly regulates the transcriptional regulatory gene phoY1. J. Bacteriol. 2007
Citation	DAHP synthase from Mycobacterium tuberculosis H37Rv: cloning, expression, and purification of functional enzyme. C. Rizzi, J. Frazzon et al. Protein Expr. Purif. 2005	jjmcfadden		15721768	Inferred from direct assay
Term	EC:2.5.1.54 3-deoxy-7-phosphoheptulonate synthase. - NR	jjmcfadden	NR		Inferred from direct assay C. Rizzi, J. Frazzon et al. DAHP synthase from Mycobacterium tuberculosis H37Rv: cloning, expression, and purification of functional enzyme. Protein Expr. Purif. 2005

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