Rv1656 (argF)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ornithine carbamoyltransferase
- REFSEQ: ornithine carbamoyltransferase
- PATRIC: Ornithine carbamoyltransferase (EC 2.1.3.3)
- TUBERCULIST: Probable ornithine carbamoyltransferase anabolic ArgF
- NCBI: Probable ornithine carbamoyltransferase, anabolic ArgF
- updated information (H37Rv4):
  - gene name: argF
  - function:
  - reference: Tiwari (2018) PMID: 30143580
Type: Not Target
Start: 1869922
End: 1870845
Operon:

Trans-membrane region:
Role: I.D.1 - Glutamate family
GO terms:
- GO:0042450 - arginine biosynthetic process via ornithine (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016743 - carboxyl- or carbamoyltransferase activity (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016597 - amino acid binding (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0006591 - ornithine metabolic process (Uniprot)
- GO:0006526 - arginine biosynthetic process (Uniprot)
- GO:0006520 - cellular amino acid metabolic process (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0004585 - ornithine carbamoyltransferase activity (Uniprot)
- GO:0000050 - urea cycle (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- ORN[c] + CAP[c] -> PI[c] + CITR[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: 2p2g, 2i6u
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2P2G	100%	Mycobacterium tuberculosis	Crystal Structure of Ornithine Carbamoyltransferase from Mycobacterium Tuberculosis (Rv1656): Orthorhombic Form
2I6U	100%	Mycobacterium tuberculosis	Crystal Structure of Ornithine Carbamoyltransferase complexed with Carbamoyl Phosphate and L-Norvaline from Mycobacterium tuberculosis (Rv1656) at 2.2 A
3GD5	53%	Gloeobacter violaceus	Crystal structure of ornithine carbamoyltransferase from Gloeobacter violaceus
1PVV	52%	Pyrococcus furiosus	Refined Structure of Pyrococcus furiosus Ornithine Carbamoyltransferase at 1.87 A
1A1S	52%	Pyrococcus furiosus	ORNITHINE CARBAMOYLTRANSFERASE FROM PYROCOCCUS FURIOSUS
4OH7	48%	Brucella melitensis	Crystal structure of Ornithine carbamoyltransferase from Brucella melitensis
4EP1	45%	Bacillus anthracis	Crystal structure of anabolic ornithine carbamoyltransferase from Bacillus anthracis
4NF2	44%	Bacillus anthracis	Crystal structure of anabolic ornithine carbamoyltransferase from Bacillus anthracis in complex with carbamoyl phosphate and L-norvaline
4F2G	44%	Burkholderia thailandensis	The Crystal Structure of Ornithine carbamoyltransferase from Burkholderia thailandensis E264
2EF0	44%	Thermus thermophilus	Crystal structure of ornithine carbamoyltransferase from thermus thermophilus

Links to additional information on argF:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.937 (from Jeremy Rock's lab)

Amino Acid Sequence

VIRHFLRDDDLSPAEQAEVLELAAELKKDPVSRRPLQGPRGVAVIFDKNSTRTRFSFELGIAQLGGHAVVVDSGSTQLGRDETLQDTAKVLSRYVDAIVW
RTFGQERLDAMASVATVPVINALSDEFHPCQVLADLQTIAERKGALRGLRLSYFGDGANNMAHSLLLGGVTAGIHVTVAAPEGFLPDPSVRAAAERRAQD
TGASVTVTADAHAAAAGADVLVTDTWTSMGQENDGLDRVKPFRPFQLNSRLLALADSDAIVLHCLPAHRGDEITDAVMDGPASAVWDEAENRLHAQKALL
VWLLERS

(Nucleotide sequence available on KEGG)

Additional Information

Tiwari S, van Tonder AJ, Vilchèze C, Mendes V, Thomas SE, Malek A,
Chen B, Chen M, Kim J, Blundell TL, Parkhill J, Weinrick B, Berney M,
Jacobs WR Jr. Arginine-deprivation-induced oxidative damage sterilizes
Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2018 Sep
25;115(39):9779-9784. doi: 10.1073/pnas.1808874115. Epub 2018 Aug
24. PMID: 30143580; PMCID: PMC6166831.

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)	1.68 (0.35)	0.94 (0.36)
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

Rv1656/argF, gene len: 923 bp, num TA sites: 5

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, cofactors)
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:

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0081 (-) (Upstream of operon)
- Rv1657 (argR) (Upstream of operon)
- Rv3133c (devR) (Upstream of operon)

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:
- Rv0238 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Regulatory Rv1657	vashishtrv	IDA		Structural Analysis LT. Cherney, MM. Cherney et al. The structure of the arginine repressor from Mycobacterium tuberculosis bound with its DNA operator and Co-repressor, L-arginine. J. Mol. Biol. 2009
Interaction	Regulatory Rv1657	vashishtrv	IDA		Structural Analysis LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Regulatory Rv1657	shahanup86	IDA		Spectrophotometric LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Regulatory Rv1657	shahanup86	IDA		Structural Analysis LT. Cherney, MM. Cherney et al. The structure of the arginine repressor from Mycobacterium tuberculosis bound with its DNA operator and Co-repressor, L-arginine. J. Mol. Biol. 2009
Interaction	Regulatory Rv1657	shahanup86	IDA		Structural Analysis LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Regulatory Rv1657	vashishtrv	IDA		Spectrophotometric LT. Cherney, MM. Cherney et al. The structure of the arginine repressor from Mycobacterium tuberculosis bound with its DNA operator and Co-repressor, L-arginine. J. Mol. Biol. 2009
Interaction	Regulatory Rv1657	vashishtrv	IDA		Spectrophotometric LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Citation	Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. LT. Cherney, MM. Cherney et al. Acta Crystallogr. D Biol. Crystallogr. 2008	priti.priety	NAS	18703843	Structural Analysis
Interaction	Regulatory Rv1657	priti.priety	NAS		Structural Analysis LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Citation	Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. LT. Cherney, MM. Cherney et al. Acta Crystallogr. D Biol. Crystallogr. 2008	ashwinigbhat	NAS	18703843	Structural Analysis
Interaction	Regulatory Rv1657	ashwinigbhat	NAS		Structural Analysis LT. Cherney, MM. Cherney et al. Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis. Acta Crystallogr. D Biol. Crystallogr. 2008
Interaction	Regulatory Rv1657	shahanup86	IDA		Spectrophotometric LT. Cherney, MM. Cherney et al. The structure of the arginine repressor from Mycobacterium tuberculosis bound with its DNA operator and Co-repressor, L-arginine. J. Mol. Biol. 2009
Interaction	RegulatedBy Rv1657	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 Rv1657	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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