Gene Rv1915 (icl2a)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in glyoxylate bypass, an alternative to the tricarboxylic acid cycle [catalytic activity: isocitrate = succinate + glyoxylate]. |
| Product | Probable isocitrate lyase AceAa [first part] (isocitrase) (isocitratase) (Icl) |
| Comments | Rv1915, (MTCY180.03c), len: 367 aa. Probable aceAa, isocitrate lyase (see citations below). Highly similar to the N-terminus of ACEA_MYCLE isocitrate lyase from Mycobacterium leprae (606 aa), FASTA results: opt: 3314, E(): 0, (86.5% identity in 572 aa overlap). Contains PS00161 Isocitrate lyase signature. Although this ORF and the downstream ORF representing the C-terminal half of aceA could be joined by a frameshift, no error is apparent in the cosmid, or in a seqencing read from the genome of H37Rv. As the downstream ORF has a RBS and transcriptional start immediately following the stop of this ORF, it is possible that they are expressed as two separate modules. In Mycobacterium tuberculosis strain CDC1551, aceA exists as a single gene, MT1966: the corresponding protein has been purified experimentally and seems have an active isocitrate lyase activity (see Honer et al., 1999). For Mycobacterium tuberculosis strain H37Rv, immunoblot assay didn't detect AceAa or AceAb products (see Honer et al., 1999) but mRNA of AceAa|Rv1915 has been detected (see Betts et al., 2002); so AceAb|Rv1916 could be a pseudogene. Icl2 has 2-methyl-isocitrate lyase (MCL) activity in M. tuberculosis Erdman (See Munoz-Elias et al., 2006). |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | Identified by mass spectrometry in M. tuberculosis H37Rv-infected guinea pig lungs at 30 days but not 90 days (See Kruh et al., 2010). Identified by mass spectrometry in whole cell lysates of M. tuberculosis H37Rv but not the culture filtrate or membrane protein fraction (See de Souza et al., 2011). |
| Transcriptomics | mRNA identified by microarray analysis and up-regulated after 4h, 24h and 96h of starvation (see Betts et al., 2002). |
| Mutant | Non-essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Non-essential gene for in vitro growth of H37Rv, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Non essential gene by Himar1 transposon mutagenesis in H37Rv and CDC1551 strains (see Sassetti et al., 2003 and Lamichhane et al., 2003). Non-essential gene for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). Found to be deleted (partially or completely) in one or more clinical isolates (See Tsolaki et al., 2004). M. tuberculosis Erdman icl1 icl2 mutant is unable to grow on fatty acids, in mice, in macrophages (See Munoz-Elias et al., 2005). Check for mutants available at TARGET website |
Coordinates
| Type | Start | End | Orientation |
|---|---|---|---|
| CDS | 2160463 | 2161566 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv1915|aceAa
MAIAETDTEVHTPFEQDFEKDVAATQRYFDSSRFAGIIRLYTARQVVEQRGTIPVDHIVAREAAGAFYERLRELFAARKSITTFGPYSPGQAVSMKRMGIEAIYLGGWATSAKGSSTEDPGPDLASYPLSQVPDDAAVLVRALLTADRNQHYLRLQMSERQRAATPAYDFRPFIIADAGTGHGGDPHVRNLIRRFVEVGVPGYHIEDQRPGTKKCGHQGGKVLVPSDEQIKRLNAARFQLDIMRVPGIIVARTDAEAANLIDSRADERDQPFLLGATKLDVPSYKSCFLAMVRRFTNWASRSSMVIFSMRLATASTRRPAVGLSAKAFSAWSPTRSTRGGRTASSRSTAFSTRSSRGSWRPGRTTRA
Bibliography
- Honer zu Bentrup K, Miczak A, Swenson DL and Russell DG [1999]. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. Homolog Product Biochemistry
- McKinney JD et al. [2000]. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Mutant
- Betts JC et al. [2002]. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Transcriptome
- Lamichhane G et al. [2003]. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Mutant
- Sassetti CM et al. [2003]. Genes required for mycobacterial growth defined by high density mutagenesis. Mutant
- Tsolaki AG, Hirsh AE, DeRiemer K, Enciso JA, Wong MZ, Hannan M, Goguet de la Salmoniere YO, Aman K, Kato-Maeda M and Small PM [2004]. Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains. Mutant
- Muñoz-Elías EJ et al. [2005]. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Mutant
- Munoz-Elias EJ, Upton AM, Cherian J and McKinney JD [2006]. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Function
- Kruh NA et al. [2010]. Portrait of a pathogen: the Mycobacterium tuberculosis proteome in vivo. Proteomics
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- Griffin JE et al. [2011]. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. Mutant
- DeJesus MA et al. [2017]. Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. Mutant
- Minato Y et al. [2019]. Genomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic Pathways. Mutant
