Rv0404 (fadD30)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: fatty-acid-CoA ligase fadD30
- REFSEQ: acyl-CoA synthetase
- PATRIC: Long-chain-fatty-acid--CoA ligase (EC 6.2.1.3)
- TUBERCULIST: Fatty-acid-AMP ligase FadD30 (fatty-acid-AMP synthetase) (fatty-acid-AMP synthase)
- NCBI: Fatty-acid-AMP ligase FadD30 (fatty-acid-AMP synthetase) (fatty-acid-AMP synthase)
- updated information (H37Rv4):
  - gene name: fadD30
  - function:
  - reference:
Coordinates in H37Rv: 483977 - 485734
Gene length: 1758 bp (with stop codon), 585 aa (without stop codon)
Operon:

Trans-membrane region:
Role: I.A.3 - Fatty acids
GO terms:
- GO:0071766 - Actinobacterium-type cell wall biogenesis (Uniprot)
- GO:0070566 - adenylyltransferase activity (Uniprot)
- GO:0052556 - positive regulation by symbiont of host immune response (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0016874 - ligase activity (Uniprot)
- GO:0008610 - lipid biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (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:0005524 - ATP binding (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
- GO:0000166 - nucleotide binding (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):

PDB	aa ident	species	PDB title
3E53	45%	Mycobacterium tuberculosis	Crystal structure of N-terminal domain of a Fatty Acyl AMP Ligase FAAL28 from Mycobacterium tuberculosis
3T5A	45%	Mycobacterium tuberculosis	Crystal structure of N-terminal domain of FAAL28 G330W mutant from Mycobacterium tuberculosis
8IQU	44%	Mycobacterium tuberculosis	Structure of MtbFadD23 with PhU-AMS
8HDF	44%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Full length crystal structure of mycobacterium tuberculosis FadD23 in complex with ANP and PLM
8HD4	44%	Mycobacterium tuberculosis H37Rv	Full-length crystal structure of mycobacterium tuberculosis FadD23 in complex with AMPC16
8HCZ	44%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	N-terminal domain structure of mycobacterium tuberculosis FadD23
5HM3	36%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	2.25 Angstrom Resolution Crystal Structure of Long-chain-fatty-acid-AMP Ligase FadD32 from Mycobacterium tuberculosis in complex with Inhibitor 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine
5ICR	35%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	2.25 Angstrom Resolution Crystal Structure of Fatty-Acid-CoA Ligase (FadD32) from Mycobacterium smegmatis in complex with Inhibitor 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine.
5EY8	35%	Mycobacterium smegmatis	Structure of FadD32 from Mycobacterium smegmatis complexed to AMPC20
5D6J	35%	Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)	Crystal structure of a mycobacterial protein

Links to additional information on fadD30:
- 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 = 0.378 (from Jeremy Rock's lab)

Amino Acid Sequence

MSVISTLRDRATTTPSDEAFVFMDYDTKTGDQIDRMTWSQLYSRVTAVSAYLISYGRHADRRRTAAISAPQGLDYVAGFLGALCAGWTPVPLPEPLGSLR
DKRTGLAVLDCAADVVLTTSQAETRVRATIATHGASVTTPVIALDTLDEPSGDNCDLDSQLSDWSSYLQYTSGSTANPRGVVLSMRNVTENVDQIIRNYF
RHEGGAPRLPSSVVSWLPLYHDMGLMVGLFIPLFVGCPVILTSPEAFIRKPARWMQLLAKHQAPFSAAPNFAFDLAVAKTSEEDMAGLDLGHVNTIINGA
EQVQPNTITKFLRRFRPYNLMPAAVKPSYGMAEAVVYLATTKAGSPPTSTEFDADSLARGHAELSTFETERATRLIRYHSDDKEPLLRIVDPDSNIELGP
GRIGEIWIHGKNVSTGYHNADDALNRDKFQASIREASAGTPRSPWLRTGDLGFIVGDEFYIVGRMKDLIIQDGVNHYPDDIETTVKEFTGGRVAAFSVSD
DGVEHLVIAAEVRTEHGPDKVTIMDFSTIKRLVVSALSKLHGLHVTDFLLVPPGALPKTTSGKISRAACAKQYGANKLQRVATFP

(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

Rv0404/fadD30, gene len: 1757 bp, num TA sites: 87

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	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	uncertain	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.6)	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=0.372)	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=0.98)	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 Rv0404: 0.844238234
- lineage-specific pN/pS in L1: 0.929885591
- lineage-specific pN/pS in L2: 0.721677488
- lineage-specific pN/pS in L3: 0.92844614
- lineage-specific pN/pS in L4: 0.837440825

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)	1.52 (0.81)
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:
- Rv0023 (-) (Direct binding)
- Rv0081 (-) (Direct binding)
- Rv0465c (-) (Direct binding)
- Rv3249c (-) (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
Rv0404/fadD30	Rv3249c/-	2.14
Rv0404/fadD30	Rv3058c/-	-1.06
Rv0404/fadD30	Rv2884/-	-1.07
Rv0404/fadD30	Rv1358/-	-1.18
Rv0404/fadD30	Rv0353/hspR	-1.2
Rv0404/fadD30	Rv0238/fdmR	-1.27
Rv0404/fadD30	Rv3849/espR	-1.3
Rv0404/fadD30	Rv0023/-	-2.26

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Rv3249c (-)
Downregulates:
- Does not downregulate other genes.
Downregulated by:

TB Genome Annotation Portal