Rv0649 (fabD2)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: [acyl-carrier-protein] S-malonyltransferase
- REFSEQ: malonyl CoA-acyl carrier protein transacylase
- PATRIC: POSSIBLE MALONYL COA-ACYL CARRIER PROTEIN TRANSACYLASE FABD2 (MCT) (EC 2.3.1.39)
- TUBERCULIST: Possible malonyl CoA-acyl carrier protein transacylase FabD2 (MCT)
- NCBI: Possible malonyl CoA-acyl carrier protein transacylase FabD2 (MCT)
- updated information (H37Rv4):
  - gene name: fabD2
  - function:
  - reference:
Coordinates in H37Rv: 746363 - 747037
Gene length: 675 bp (with stop codon), 224 aa (without stop codon)
Operon:

Trans-membrane region:
Role: I.H.1 - Synthesis of fatty and mycolic acids
GO terms:
- GO:0042759 - long-chain fatty acid biosynthetic process (Uniprot)
- GO:0004314 - [acyl-carrier-protein] S-malonyltransferase 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:
Search for Latest Homologs in PDB
Top 10 Homologs in PDB (as of Apr 2026): (none with >35% aa id)
Links to additional information on fabD2:
- 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 = 0.616 (from Jeremy Rock's lab)

Amino Acid Sequence

MSGRSRLPGSSSRRDAARIVAERVVATVAGVAVAVDEVDAAEARLRDGPRAAALPASGTSEGRQLRRWLTQLIVTERVVAAEAAARGLTAAGAPAEADLL
PDATARLEIGSVAAAVLADPLARALFAAVTARVAVTDDAVADYHARNPLRFAAPCPGQHGWRAPAAAAPPLDQVRRAITEHLLGAARRRAFRVWLDARRN
ALVVLAPGYEHPGDPRQPDNTRRH

(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

Rv0649/fabD2, gene len: 674 bp, num TA sites: 4

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-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	non-essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	non-essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.04)	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	non-essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	non-essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.637)	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	non-essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, cofactors)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=3.38)	YM rich vs minimal medium	resampling

Analysis of Positive Selection in Clinical Isolates new

data from Culviner et al (2025) (55,259 Mtb clinical isolates)
- overall pN/pS for Rv0649: 0.896143531
- lineage-specific pN/pS in L1: 0.521652178
- lineage-specific pN/pS in L2: 0.758766804
- lineage-specific pN/pS in L3: 0.946154558
- lineage-specific pN/pS in L4: 1.091939597

Analysis of dN/dS (omega) in a global collection of 10k Mtb clinical isolates using GenomegaMap (Window model)
clinical isolates collection: global set of 10,626 Mtb genomes
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.

	global set of 10,626 Mtb clinical isolates
under significant positive selection?	NO
omega peak height (95%CI lower bound)	1.41 (0.7)
codons under selection
omega plots
genetic variants*	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

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: see table of TFOE interactions below

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:
- Rv1049 (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01

gene	dysregulated by OE of	LFC
Rv0649/fabD2	Rv3286c/sigF	1.5
Rv0649/fabD2	Rv3849/espR	1.46
Rv0649/fabD2	Rv2595/vapB40	1.18

Upregulates:
- Does not upregulate other genes.
Upregulated by:
Downregulates:
- Does not downregulate other genes.
Downregulated by:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv1221	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.. R. Manganelli, MI. Voskuil et al. The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol. Microbiol. 2001
Name	MALONYL CoA-ACYL CARRIER PROTEIN TRANSACYLASE	mjackson	ISS		FAS-I->FAS-II
Name	MALONYL CoA-ACYL CARRIER PROTEIN TRANSACYLASE	mjackson	IDA		FAS-I->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:6.4.1.2 Acetyl-CoA carboxylase. - 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:2.3.1.39 [Acyl-carrier-protein] S-malonyltransferase. - 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:2.3.1.38 [Acyl-carrier-protein] S-acetyltransferase. - 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

TB Genome Annotation Portal