Rv1483 (fabG1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: 3-oxoacyl-[acyl-carrier-protein] reductase
- REFSEQ: 3-oxoacyl-[acyl-carrier protein] reductase FabG1
- PATRIC: 3-oxoacyl-[acyl-carrier protein] reductase (EC 1.1.1.100)
- TUBERCULIST: 3-oxoacyl-[acyl-carrier protein] reductase FabG1 (3-ketoacyl-acyl carrier protein reductase) (mycolic acid biosynthesis a protein)
- NCBI: 3-oxoacyl-[acyl-carrier protein] reductase FabG1 (3-ketoacyl-acyl carrier protein reductase) (mycolic acid biosynthesis a protein)
- updated information (H37Rv4):
  - gene name: fabG1
  - function: aka 'mabA'
  - reference:
Type: Not Target
Start: 1673440
End: 1674183
Operon:

Trans-membrane region:
Role: I.H.1 - Synthesis of fatty and mycolic acids
GO terms:
- GO:0102132 - 3-oxo-pimeloyl-[acp] methyl ester reductase activity (Uniprot)
- GO:0102131 - 3-oxo-glutaryl-[acp] methyl ester reductase activity (Uniprot)
- GO:0071768 - mycolic acid biosynthetic process (Uniprot)
- GO:0070402 - NADPH binding (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0046459 - short-chain fatty acid metabolic process (Uniprot)
- GO:0018454 - acetoacetyl-CoA reductase activity (Uniprot)
- GO:0016491 - oxidoreductase activity (Uniprot)
- GO:0006633 - fatty acid biosynthetic process (Uniprot)
- GO:0006631 - fatty acid metabolic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005515 - protein binding (Uniprot)
- GO:0004316 - 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity (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: 3lls, 2ntn, 1uzn, 1uzm, 1uzl
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
1UZL	99%	MYCOBACTERIUM TUBERCULOSIS	MabA from Mycobacterium tuberculosis
1UZN	98%	MYCOBACTERIUM TUBERCULOSIS	MabA from Mycobacterium tuberculosis
1UZM	98%	MYCOBACTERIUM TUBERCULOSIS	MabA from Mycobacterium tuberculosis
2NTN	98%	Mycobacterium tuberculosis H37Rv	Crystal structure of MabA-C60V/G139A/S144L
5OVL	86%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	crystal structure of MabA bound to NADP+ from M. smegmatis
5OVK	86%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Crystal structure MabA bound to NADPH from M. smegmatis
5OVJ	86%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Structure of the apo form of Mycobacterium smegmatis MabA
2NM0	57%	Streptomyces coelicolor	Crystal Structure of SCO1815: a Beta-Ketoacyl-Acyl Carrier Protein Reductase from Streptomyces coelicolor A3(2)
3WOH	44%	Streptomyces	Structure of Ketoreductase SiaM from Streptomyces sp. A7248
1Q7B	44%	Escherichia coli	The structure of betaketoacyl-[ACP] reductase from E. coli in complex with NADP+

Links to additional information on fabG1:
- KEGG - nucleotide and amino acid sequences of gene
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -11.068 (from Jeremy Rock's lab)
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

VTATATEGAKPPFVSRSVLVTGGNRGIGLAIAQRLAADGHKVAVTHRGSGAPKGLFGVECDVTDSDAVDRAFTAVEEHQGPVEVLVSNAGLSADAFLMRM
TEEKFEKVINANLTGAFRVAQRASRSMQRNKFGRMIFIGSVSGSWGIGNQANYAASKAGVIGMARSIARELSKANVTANVVAPGYIDTDMTRALDERIQQ
GALQFIPAKRVGTPAEVAGVVSFLASEDASYISGAVIPVDGGMGMGH

(Nucleotide sequence available on KEGG)

Additional Information

aka MabA

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)	0.61 (0.01)	1.01 (0.22)
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

Rv1483/fabG1, gene len: 743 bp, num TA sites: 13

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	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	non-essential	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:
- Rv0818 (-)

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

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

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:
- Rv0818 (-)

Property	Value	Creator	Evidence	PMID	Comment
Name	-Ketoacyl-ACP reductase/3-OXOACYL-[ACYL-CARRIER PROTEIN] REDUCTASE	mjackson	IMP		FAS-II
Name	-Ketoacyl-ACP reductase/3-OXOACYL-[ACYL-CARRIER PROTEIN] REDUCTASE	mjackson	IDA		FAS-II
Citation	Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. K. Takayama, C. Wang et al. Clin. Microbiol. Rev. 2005	jjmcfadden		15653820	Inferred from direct assay
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	jjmcfadden	NR		Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Term	EC:2.3.1.41 Beta-ketoacyl-acyl-carrier-protein synthase I. - NR	jjmcfadden	NR		Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Term	EC:1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase. - NR	jjmcfadden	NR		Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005

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