Rv3285 (accA3)
Current annotations:
TBCAP: (community-based annotations - see table at bottom of page )
TBDB: acetyl-/propionyl-coenzyme A carboxylase alpha chain
REFSEQ: bifunctional acetyl-/propionyl-coenzyme A carboxylase subunit alpha
PATRIC: Biotin carboxylase of acetyl-CoA carboxylase (EC 6.3.4.14) / Biotin carboxyl carrier protein of acetyl-CoA carboxylase
TUBERCULIST: Probable bifunctional protein acetyl-/propionyl-coenzyme A carboxylase (alpha chain) AccA3: biotin carboxylase + biotin carboxyl carrier protein (BCCP)
NCBI: Probable bifunctional protein acetyl-/propionyl-coenzyme A carboxylase (alpha chain) AccA3: biotin carboxylase + biotin carboxyl carrier protein (BCCP)
updated information (H37Rv4):
gene name: accA3
function:
reference:
Coordinates in H37Rv: 3666357 - 3668159
Gene length: 1803 bp (with stop codon), 600 aa (without stop codon)
Operon:
Trans-membrane region:
Role: I.H.1 - Synthesis of fatty and mycolic acids
GO terms:
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 5MLK 99% Mycobacterium tuberculosis H37Rv Biotin dependent carboxylase AccA3 dimer from Mycobacterium tuberculosis (Rv3285) 9YX5 85% Mycolicibacterium smegmatis MC2 155 Structure of the long chain acyl-CoA carboxylase complex from Mycobacterium smegmatis with MSMEG_0435-MSMEG_0436 bound 9YX4 85% Mycolicibacterium smegmatis MC2 155 Structure of the long chain acyl-CoA carboxylase complex from Mycobacterium smegmatis with ATP, bicarbonate, arachidoyl-CoA, and propionyl-CoA 9YX2 85% Mycolicibacterium smegmatis MC2 155 Structure of the long chain acyl-CoA carboxylase complex from Mycobacterium smegmatis with ATP, bicarbonate, and propionyl-CoA 9YX1 85% Mycolicibacterium smegmatis MC2 155 Structure of the long chain acyl-CoA carboxylase complex from Mycobacterium smegmatis 8HZ4 54% Chloroflexus aurantiacus (strain ATCC 29366 / DSM 635 / J-10-fl) The tetrameric structure of biotin carboxylase from Chloroflexus aurantiacus in complex with bicarbonate 9EB8 50% Ankistrodesmus falcatus Crystal Structure of Biotin Carboxylase from Ankistrodesmus in Complex with ADP 9EB7 50% Ankistrodesmus falcatus Crystal Structure of Biotin Carboxylase from Ankistrodesmus 9AAL 48% None Pennycress biotin carboxylase tetramer integrative model 8HZ5 47% Chloroflexus aurantiacus (strain ATCC 29366 / DSM 635 / J-10-fl) The homodimer of a biotin carboxylase isoform from chloroflexus aurantiacus
Links to additional information on accA3:
Amino Acid Sequence
VASHAGSRIARISKVLVANRGEIAVRVIRAARDAGLPSVAVYAEPDAESPHVRLADEAFALGGQTSAESYLDFAKILDAAAKSGANAIHPGYGFLAENAD
FAQAVIDAGLIWIGPSPQSIRDLGDKVTARHIAARAQAPLVPGTPDPVKGADEVVAFAEEYGLPIAIKAAHGGGGKGMKVARTIDEIPELYESAVREATA
AFGRGECYVERYLDKPRHVEAQVIADQHGNVVVAGTRDCSLQRRYQKLVEEAPAPFLTDFQRKEIHDSAKRICKEAHYHGAGTVEYLVGQDGLISFLEVN
TRLQVEHPVTEETAGIDLVLQQFRIANGEKLDITEDPTPRGHAIEFRINGEDAGRNFLPAPGPVTKFHPPSGPGVRVDSGVETGSVIGGQFDSMLAKLIV
HGADRAEALARARRALNEFGVEGLATVIPFHRAVVSDPAFIGDANGFSVHTRWIETEWNNTIEPFTDGEPLDEDARPRQKVVVEIDGRRVEVSLPADLAL
SNGGGCDPVGVIRRKPKPRKRGAHTGAAASGDAVTAPMQGTVVKFAVEEGQEVVAGDLVVVLEAMKMENPVTAHKDGTITGLAVEAGAAITQGTVLAEIK
(
Nucleotide sequence available on
KEGG )
Additional Information
MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb
TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions
Rv3285/accA3,
gene len: 1802 bp, num TA sites: 27
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 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 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=0.021) 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, cofactors)
differentially essential in YM rich medium Minato 2019 mSys NO (LFC=0.0) 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 Rv3285: 0.393215112
lineage-specific pN/pS in L1: 0.365735524
lineage-specific pN/pS in L2: 0.348198075
lineage-specific pN/pS in L3: 0.352461725
lineage-specific pN/pS in L4: 0.434200381
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) 1.23 (0.52)
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.
accA3 KO Metabolomic Profile
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
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
Translation, ribosomal structure and biogenesis
Cell wall/membrane/envelope biogenesis
Replication, recombination and repair
Posttranslational modification, protein turnover, chaperones
Secondary metabolites biosynthesis, transport and catabolism
Inorganic ion transport and metabolism
General function prediction only
Intracellular trafficking, secretion, and vesicular transport
Signal transduction mechanisms
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).
Binds To:
No bindings to other targets were found.
Bound By:
No bindings from other targets were found.
Binds To:
No bindings to other targets were found.
Bound By:
TFOE = Transcription Factor Over-Expression study
significance criteria used in paper: greater than 2-fold change (|LFC|>=1.0) and Padj<0.01
no significant interactions found
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
Interaction PhysicalInteraction Rv3801c sourish10 TAS Affinity purification (Physical interaction)SK. Parker, RM. Barkley et al. Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin. PLoS ONE 2009
Name Biotin-dependent propionyl-CoA carboxylase alpha-3 subunit involved in the synthesis of methyl-malonyl-CoA required for the biosynthesis of multiple methyl-branched fatty acids; the enzyme complex made of AccA3-AccD5-AccE5 shows a clear substrate preference for propionyl-CoA compared with acetyl-CoA (used in the generation of malonyl-CoA) mjackson IDA Claisen-type condensation
Citation Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv. TJ. Oh, J. Daniel et al. J. Biol. Chem. 2006 mjackson 16354663 Biotin-dependent propionyl-CoA carboxylase alpha-3 subunit involved in the synthesis of methyl-malonyl-CoA required for the biosynthesis of multiple methyl-branched fatty acids (enzymatic); the enzyme complex made of AccA3-AccD5-AccE5 shows a clear substrate preference for propionyl-CoA compared with acetyl-CoA (used in the generation of malonyl-CoA)
Other TBPWY:Methyl-malonyl-CoA synthesis mjackson Biotin-dependent propionyl-CoA carboxylase alpha-3 subunit involved in the synthesis of methyl-malonyl-CoA required for the biosynthesis of multiple methyl-branched fatty acids (enzymatic); the enzyme complex made of AccA3-AccD5-AccE5 shows a clear substrate preference for propionyl-CoA compared with acetyl-CoA (used in the generation of malonyl-CoA)TJ. Oh, J. Daniel et al. Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv. J. Biol. Chem. 2006
Citation Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. G. Gago, D. Kurth et al. J. Bacteriol. 2006 mjackson 16385038 Biotin-dependent propionyl-CoA carboxylase alpha-3 subunit involved in the synthesis of methyl-malonyl-CoA required for the biosynthesis of multiple methyl-branched fatty acids (enzymatic); the enzyme complex made of AccA3-AccD5-AccE5 shows a clear substrate preference for propionyl-CoA compared with acetyl-CoA (used in the generation of malonyl-CoA)
Other TBPWY:Methyl-malonyl-CoA synthesis mjackson Biotin-dependent propionyl-CoA carboxylase alpha-3 subunit involved in the synthesis of methyl-malonyl-CoA required for the biosynthesis of multiple methyl-branched fatty acids (enzymatic); the enzyme complex made of AccA3-AccD5-AccE5 shows a clear substrate preference for propionyl-CoA compared with acetyl-CoA (used in the generation of malonyl-CoA)G. Gago, D. Kurth et al. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J. Bacteriol. 2006
Citation The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase components. D. Portevin, C. de Sousa-D'Auria et al. J. Biol. Chem. 2005 jjmcfadden 15632194 Inferred from direct assay
Term EC:6.4.1.2 Acetyl-CoA carboxylase. - NR jjmcfadden NR Inferred from direct assayD. Portevin, C. de Sousa-D'Auria et al. The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase components. J. Biol. Chem. 2005
Term EC:6.3.4.14 Biotin carboxylase. - NR jjmcfadden NR Inferred from direct assayD. Portevin, C. de Sousa-D'Auria et al. The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase components. J. Biol. Chem. 2005
Citation Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. authors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Trends Microbiol. 2011 extern:JZUCKER 21561773 Traceable author statement to experimental support
Term EC:6.3.4.14 Biotin carboxylase. - NR extern:JZUCKER NR Traceable author statement to experimental supportauthors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
Term EC:6.4.1.2 Acetyl-CoA carboxylase. - NR extern:JZUCKER NR Traceable author statement to experimental supportauthors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
Term EC:6.4.1.3 Propionyl-CoA carboxylase. - NR extern:JZUCKER NR Traceable author statement to experimental supportauthors,KY. Rhee,LP. de Carvalho,R. Bryk,S. Ehrt,J. Marrero,SW. Park,D. Schnappinger,A. Venugopal,C. Nathan Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier. Trends Microbiol. 2011
Citation Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. G. Gago, D. Kurth et al. J. Bacteriol. 2006 extern:JZUCKER 16385038 Inferred from mutant phenotype
Term EC:6.3.4.14 Biotin carboxylase. - NR extern:JZUCKER NR Inferred from mutant phenotypeG. Gago, D. Kurth et al. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J. Bacteriol. 2006
Term EC:6.4.1.2 Acetyl-CoA carboxylase. - NR extern:JZUCKER NR Inferred from mutant phenotypeG. Gago, D. Kurth et al. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J. Bacteriol. 2006
Term EC:6.4.1.3 Propionyl-CoA carboxylase. - NR extern:JZUCKER NR Inferred from mutant phenotypeG. Gago, D. Kurth et al. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J. Bacteriol. 2006