Rv1475c (acn)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: aconitate hydratase
- REFSEQ: aconitate hydratase
- PATRIC: Aconitate hydratase (EC 4.2.1.3) @ 2-methylisocitrate dehydratase (EC 4.2.1.99)
- TUBERCULIST: Probable iron-regulated aconitate hydratase Acn (citrate hydro-lyase) (aconitase)
- NCBI: Probable iron-regulated aconitate hydratase Acn (citrate hydro-lyase) (aconitase)
- updated information (H37Rv4):
  - gene name: acn
  - function:
  - reference:
Type: Not Target
Start: 1663215
End: 1666046
Operon:

Trans-membrane region:
Role: I.B.3 - TCA cycle
GO terms:
- GO:0051539 - 4 iron, 4 sulfur cluster binding (Uniprot)
- GO:0051536 - iron-sulfur cluster binding (Uniprot)
- GO:0047456 - 2-methylisocitrate dehydratase activity (Uniprot)
- GO:0046872 - metal ion binding (Uniprot)
- GO:0040007 - growth (Uniprot)
- GO:0030350 - iron-responsive element binding (Uniprot)
- GO:0019679 - propionate metabolic process, methylcitrate cycle (Uniprot)
- GO:0016829 - lyase activity (Uniprot)
- GO:0010039 - response to iron ion (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006099 - tricarboxylic acid cycle (Uniprot)
- GO:0005886 - plasma membrane (Uniprot)
- GO:0005829 - cytosol (Uniprot)
- GO:0005618 - cell wall (Uniprot)
- GO:0005576 - extracellular region (Uniprot)
- GO:0003994 - aconitate hydratase activity (Uniprot)
- GO:0003730 - mRNA 3'-UTR binding (Uniprot)
- GO:0003729 - mRNA binding (Uniprot)
- GO:0003723 - RNA 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 Homologs in PDB

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

PDB	aa ident	species	PDB title
3SNP	49%	Oryctolagus cuniculus	Crystal structure analysis of iron regulatory protein 1 in complex with ferritin H IRE RNA
3SN2	49%	Oryctolagus cuniculus	Crystal structure analysis of iron regulatory protein 1 in complex with transferrin receptor IRE B RNA
2B3Y	48%	Homo sapiens	Structure of a monoclinic crystal form of human cytosolic aconitase (IRP1)
2B3X	48%	Homo sapiens	Structure of an orthorhombic crystal form of human cytosolic aconitase (IRP1)
6VCD	41%	Homo sapiens	Cryo-EM structure of IRP2-FBXL5-SKP1 complex
3VBA	36%	Methanocaldococcus jannaschii	Crystal structure of methanogen 3-isopropylmalate isomerase small subunit

Links to additional information on acn:
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -2.181 (from Jeremy Rock's lab)
- BioCyc
- Systems Biology
- Photo of spot titer

Amino Acid Sequence

VTSKSVNSFGAHDTLKVGEKSYQIYRLDAVPNTAKLPYSLKVLAENLLRNEDGSNITKDHIEAIANWDPKAEPSIEIQYTPARVVMQDFTGVPCIVDLAT
MREAIADLGGNPDKVNPLAPADLVIDHSVIADLFGRADAFERNVEIEYQRNGERYQFLRWGQGAFDDFKVVPPGTGIVHQVNIEYLASVVMTRDGVAYPD
TCVGTDSHTTMVNGLGVLGWGVGGIEAEAAMLGQPVSMLIPRVVGFRLTGEIQPGVTATDVVLTVTEMLRQHGVVGKFVEFYGEGVAEVPLANRATLGNM
SPEFGSTAAIFPIDEETIKYLRFTGRTPEQVALVEAYAKAQGMWHDPKHEPEFSEYLELNLSDVVPSIAGPKRPQDRIALAQAKSTFREQIYHYVGNGSP
DSPHDPHSKLDEVVEETFPASDPGQLTFANDDVATDETVHSAAAHADGRVSNPVRVKSDELGEFVLDHGAVVIAAITSCTNTSNPEVMLGAALLARNAVE
KGLTSKPWVKTTIAPGSQVVNDYYDRSGLWPYLEKLGFYLVGYGCTTCIGNSGPLPEEISKAVNDNDLSVTAVLSGNRNFEGRINPDVKMNYLASPPLVI
AYALAGTMDFDFQTQPLGQDKDGKNVFLRDIWPSQQDVSDTIAAAINQEMFTRNYADVFKGDDRWRNLPTPSGNTFEWDPNSTYVRKPPYFEGMTAKPEP
VGNISGARVLALLGDSVTTDHISPAGAIKPGTPAARYLDEHGVDRKDYNSFGSRRGNHEVMIRGTFANIRLRNQLLDDVSGGYTRDFTQPGGPQAFIYDA
AQNYAAQHIPLVVFGGKEYGSGSSRDWAAKGTLLLGVRAVIAESFERIHRSNLIGMGVIPLQFPEGKSASSLGLDGTEVFDITGIDVLNDGKTPKTVCVQ
ATKGDGATIEFDAVVRIDTPGEADYYRNGGILQYVLRNILKSG

(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 *new*

Classification	Condition	Strain	Method	Reference	Notes
Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 56 non-insertions in a row out of 56 sites
Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 55 non-insertions in a row out of 56 sites
Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 1.000000; 55 non-insertions in a row out of 56 sites
Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 55 non-insertions in a row out of 56 sites
Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 1.000000; 55 non-insertions in a row out of 56 sites
Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 0.03
Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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

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

Transcription

Translation, ribosomal structure and biogenesis

Cell wall/membrane/envelope biogenesis

Replication, recombination and repair

Posttranslational modification, protein turnover, chaperones

Cell motility

Secondary metabolites biosynthesis, transport and catabolism

Inorganic ion transport and metabolism

Function unknown

General function prediction only

Intracellular trafficking, secretion, and vesicular transport

Signal transduction mechanisms

Extracellular structures

Defense mechanisms

Nuclear structure

Cytoskeleton

BioCyc Co-regulated genes based on gene expression profiling (Systems Biology, Inferelator Network)

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).

BioCyc Transcription factor binding based on ChIP-Seq (Systems Biology)

Binds To:
- No bindings to other targets were found.
Bound By:
- No bindings from other targets were found.

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv0047c (-) (Direct binding)
- Rv0678 (-) (Direct binding)
- Rv3574 (kstR) (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:
- Not downregulated by other genes.

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv3676	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv3676	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006
Citation	Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. EJ. Muoz-Elas, AM. Upton et al. Mol. Microbiol. 2006	jjmcfadden		16689789	Inferred from direct assay
Term	EC:4.2.1.99 2-methylisocitrate dehydratase. - NR	jjmcfadden	NR		Inferred from direct assay EJ. Muoz-Elas, AM. Upton et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol. Microbiol. 2006
Term	EC:4.2.1.3 Aconitate hydratase. - NR	jjmcfadden	NR		Inferred from direct assay EJ. Muoz-Elas, AM. Upton et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol. Microbiol. 2006
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:4.2.1.3 Aconitate hydratase. - NR	extern:JZUCKER	NR		Traceable author statement to experimental support authors,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	Iron-dependent RNA-binding activity of Mycobacterium tuberculosis aconitase. S. Banerjee, AK. Nandyala et al. J. Bacteriol. 2007	extern:JZUCKER		17384188	Inferred from mutant phenotype
Term	EC:4.2.1.3 Aconitate hydratase. - NR	extern:JZUCKER	NR		Inferred from mutant phenotype S. Banerjee, AK. Nandyala et al. Iron-dependent RNA-binding activity of Mycobacterium tuberculosis aconitase. J. Bacteriol. 2007

TB Genome Annotation Portal