Rv3001c (ilvC)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: ketol-acid reductoisomerase
- REFSEQ: ketol-acid reductoisomerase
- PATRIC: Ketol-acid reductoisomerase (EC 1.1.1.86)
- TUBERCULIST: Probable KETOL-acid reductoisomerase IlvC (acetohydroxy-acid isomeroreductase) (alpha-keto-beta-hydroxylacil reductoisomerase)
- NCBI: Probable KETOL-acid reductoisomerase IlvC (acetohydroxy-acid isomeroreductase) (alpha-keto-beta-hydroxylacil reductoisomerase)
- updated information (H37Rv4):
  - gene name: ilvC
  - function:
  - reference:
Type: Not Target
Start: 3359585
End: 3360586
Operon:

Trans-membrane region:
Role: I.D.7 - Branched amino acid family
GO terms:
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0050661 - NADP binding (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0009099 - valine biosynthetic process (Uniprot)
- GO:0009097 - isoleucine biosynthetic process (Uniprot)
- GO:0009082 - branched-chain amino acid biosynthetic process (Uniprot)
- GO:0008652 - cellular amino acid biosynthetic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0004455 - ketol-acid reductoisomerase activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- NADPH[c] + ABUT[c] -> NADP[c] + DIHYDROXYMETHYLPENTANOATE[c]
- NADPH[c] + ACLAC[c] -> NADP[c] + DHMVA[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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
4YPO	100%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase in complex with Mg2+
6JX2	72%	Corynebacterium glutamicum ATCC 13032	Crystal structure of Ketol-acid reductoisomerase from Corynebacterium glutamicum
6VO2	56%	Staphylococcus aureus	Crystal structure of Staphylococcus aureus ketol-acid reductoisomerase in complex with Mg, NADPH and inhibitor.
6C5N	56%	Staphylococcus aureus (strain bovine RF122 / ET3-1)	Crystal structure of Staphylococcus aureus ketol-acid reductoisomerase with hydroxyoxamate inhibitor 1
6C55	56%	Staphylococcus aureus (strain bovine RF122 / ET3-1)	Crystal structure of Staphylococcus aureus Ketol-acid Reductosimerrase with hydroxyoxamate inhibitor 3
6BUL	56%	Staphylococcus aureus (strain bovine RF122 / ET3-1)	Crystal structure of Staphylococcus aureus ketol-acid reductoisomerase with hydroxyoxamate inhibitor 2
6AQJ	56%	Staphylococcus aureus	Crystal structures of Staphylococcus aureus ketol-acid reductoisomerase in complex with two transition state analogs that have biocidal activity.
5W3K	56%	Staphylococcus aureus	Crystal structure of Staphylococcus aureus ketol-acid reductoisomerase in complex NADPH, Mg2+ and CPD
4XIY	55%	Azotobacter vinelandii	Crystal structure of ketol-acid reductoisomerase from Azotobacter
1NP3	55%	Pseudomonas aeruginosa	Crystal structure of class I acetohydroxy acid isomeroreductase from Pseudomonas aeruginosa

Links to additional information on ilvC:
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -4.944 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology

Amino Acid Sequence

MFYDDDADLSIIQGRKVGVIGYGSQGHAHSLSLRDSGVQVRVGLKQGSRSRPKVEEQGLDVDTPAEVAKWADVVMVLAPDTAQAEIFAGDIEPNLKPGDA
LFFGHGLNVHFGLIKPPADVAVAMVAPKGPGHLVRRQFVDGKGVPCLVAVEQDPRGDGLALALSYAKAIGGTRAGVIKTTFKDETETDLFGEQTVLCGGT
EELVKAGFEVMVEAGYPAELAYFEVLHELKLIVDLMYEGGLARMYYSVSDTAEFGGYLSGPRVIDAGTKERMRDILREIQDGSFVHKLVADVEGGNKQLE
ELRRQNAEHPIEVVGKKLRDLMSWVDRPITETA

(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: 0.998700; 13 non-insertions in a row out of 13 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 13 non-insertions in a row out of 13 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 13 non-insertions in a row out of 13 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999950; 13 non-insertions in a row out of 14 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.999850; 13 non-insertions in a row out of 14 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.07
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)

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:
- 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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Citation	Cloning, sequencing and expression of the ilvBNC gene cluster from Streptomyces avermitilis. authors,E. De Rossi,R. Leva,L. Gusberti,PL. Manachini,G. Riccardi Gene 1995	jjmcfadden		8529876	Inferred from direct assay
Term	EC:1.1.1.86 Ketol-acid reductoisomerase. - NR	jjmcfadden	NR		Inferred from direct assay authors,E. De Rossi,R. Leva,L. Gusberti,PL. Manachini,G. Riccardi Cloning, sequencing and expression of the ilvBNC gene cluster from Streptomyces avermitilis. Gene 1995

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