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.

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
Uncertain	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.816900; 5 non-insertions in a row out of 5 sites
Uncertain	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.925500; 5 non-insertions in a row out of 5 sites
Uncertain	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.940000; 5 non-insertions in a row out of 5 sites
Uncertain	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.912950; 5 non-insertions in a row out of 5 sites
Uncertain	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.907650; 5 non-insertions in a row out of 5 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.04
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

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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