TB Genome Annotation Portal

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:
• Type: Essential
• Start: 3666357
• End: 3668159
• Operon:


• Trans-membrane region:
  
• Role: I.H.1 - Synthesis of fatty and mycolic acids
• GO terms:
  • GO:0046872 - metal ion binding (Uniprot)
  • GO:0040007 - growth (Uniprot)
  • GO:0015977 - carbon fixation (Uniprot)
  • GO:0009317 - acetyl-CoA carboxylase complex (Uniprot)
  • GO:0005886 - plasma membrane (Uniprot)
  • GO:0005618 - cell wall (Uniprot)
  • GO:0005524 - ATP binding (Uniprot)
  • GO:0005515 - protein binding (Uniprot)
  • GO:0004658 - propionyl-CoA carboxylase activity (Uniprot)
  • GO:0003989 - acetyl-CoA carboxylase activity (Uniprot)
  • GO:0000166 - nucleotide binding (Uniprot)
• Reaction(s) (based on iSM810 metabolic model):
  • BIOTIN_CO2[c] + HEXACOSANOYL_COA[c] -> BIOTIN[c] + HEXACOSANOYL_COA_CO2[c]
  • ATP[c] + HCO3[c] + BIOTIN_BCCP[c] -> ADP[c] + PI[c] + BIOTIN_CO2[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
  5MLK	99%	Mycobacterium tuberculosis H37Rv	Biotin dependent carboxylase AccA3 dimer from Mycobacterium tuberculosis (Rv3285)
  2VQD	47%	PSEUDOMONAS AERUGINOSA	Crystal Structure of Biotin Carboxylase from Pseudomonas aeruginosa complexed with AMPCP
  2C00	47%	PSEUDOMONAS AERUGINOSA	Crystal Structure of Biotin Carboxylase from Pseudomonas aeruginosa in apo form
  6OJH	47%	Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)	Crystal Structure of Haemophilus Influenzae Biotin Carboxylase Complexed with (R)-7-(3-aminopyrrolidin-1-yl)-6-(naphthalen-1-yl)pyrido[2,3-d]pyrimidin-2-amine
  6OI8	47%	Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)	Crystal Structure of Haemophilus Influenzae Biotin Carboxylase Complexed with 7-((1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hexan-3-yl)-6-(2-chloro-6-(pyridin-3-yl)phenyl)pyrido[2,3-d]pyrimidin-2-amine
  4RZQ	47%	Haemophilus influenzae Rd KW20	Structural Analysis of Substrate, Reaction Intermediate and Product Binding in Haemophilus influenzae Biotin Carboxylase
  4MV9	47%	Haemophilus influenzae	Crystal Structure of Biotin Carboxylase from Haemophilus influenzae in Complex with Bicarbonate
  4MV8	47%	Haemophilus influenzae	Crystal Structure of Biotin Carboxylase from Haemophilus influenzae in Complex with AMPPCP and Phosphate
  4MV7	47%	Haemophilus influenzae	Crystal Structure of Biotin Carboxylase form Haemophilus influenzae in Complex with Phosphonoformate
  4MV6	47%	Haemophilus influenzae	Crystal Structure of Biotin Carboxylase from Haemophilus influenzae in Complex with Phosphonoacetamide

• Links to additional information on accA3:
  • TBDB (updated)
  • Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
  • UniProt
  • AlphaFold model
  • Vulnerability = -13.378 (from Jeremy Rock's lab)
  • KEGG - nucleotide and amino acid sequences of gene
  • Mycobrowser
  • PATRIC
  • BioCyc
  • Systems Biology

Amino Acid Sequence

VASHAGSRIARISKVLVANRGEIAVRVIRAARDAGLPSVAVYAEPDAESPHVRLADEAFALGGQTSAESYLDFAKILDAAAKSGANAIHPGYGFLAENAD
FAQAVIDAGLIWIGPSPQSIRDLGDKVTARHIAARAQAPLVPGTPDPVKGADEVVAFAEEYGLPIAIKAAHGGGGKGMKVARTIDEIPELYESAVREATA
AFGRGECYVERYLDKPRHVEAQVIADQHGNVVVAGTRDCSLQRRYQKLVEEAPAPFLTDFQRKEIHDSAKRICKEAHYHGAGTVEYLVGQDGLISFLEVN
TRLQVEHPVTEETAGIDLVLQQFRIANGEKLDITEDPTPRGHAIEFRINGEDAGRNFLPAPGPVTKFHPPSGPGVRVDSGVETGSVIGGQFDSMLAKLIV
HGADRAEALARARRALNEFGVEGLATVIPFHRAVVSDPAFIGDANGFSVHTRWIETEWNNTIEPFTDGEPLDEDARPRQKVVVEIDGRRVEVSLPADLAL
SNGGGCDPVGVIRRKPKPRKRGAHTGAAASGDAVTAPMQGTVVKFAVEEGQEVVAGDLVVVLEAMKMENPVTAHKDGTITGLAVEAGAAITQGTVLAEIK

Additional Information

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)	1.2 (0.25)	1.07 (0.34)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link