Gene Rv0467 (icl, aceA)
in Mycobacterium tuberculosis H37Rv
General annotation
| Type | CDS |
| Function | Involved in glyoxylate bypass (at the first step), an alternative to the tricarboxylic acid cycle (in bacteria, plants, and fungi) [catalytic activity: isocitrate = succinate + glyoxylate]. Involved in the persistence in the host. |
| Product | Isocitrate lyase Icl (isocitrase) (isocitratase) |
| Comments | Rv0467, (MTV038.11), len: 428 aa. Icl1, isocitrate lyase (see citations below), highly similar to many, closest to Z29367|RFISCILY_1 from R. fascians (429 aa), FASTA scores: opt: 2359, E(): 0, (80.7% identity in 429 aa overlap). Belongs to the isocitrate lyase family. Has 2-methyl-isocitrate lyase (MCL) activity in M. tuberculosis Erdman (See Munoz-Elias et al., 2006; Gould et al., 2006). Predicted possible vaccine candidate (See Zvi et al., 2008). |
| Functional category | Intermediary metabolism and respiration |
| Proteomics | Identified in the culture supernatant of M. tuberculosis H37Rv using mass spectrometry (See Mattow et al., 2003). Identified in the cytosol and cell membrane fraction of M. tuberculosis H37Rv using 2DLC/MS (See Mawuenyega et al., 2005). Identified by mass spectrometry in the culture filtrate and whole cell lysates of M. tuberculosis H37Rv but not the membrane protein fraction (See de Souza et al., 2011). |
| Transcriptomics | mRNA identified by microarray analysis and real-time RT-PCR; transcription up-regulated at low pH in vitro conditions, which may mimic an environmental signal encountered by phagocytosed bacteria (see Miczak et al., 2000). Also identified by SCOTS method, 48h and 110h after infection of cultured human primary macrophages (see Graham & Clark-Curtiss 1999). And mRNA level (identified by real-time quantitative RT-PCR) increased 24 and 72h after cultured macrophages infection (see Dubnau et al., 2002). mRNA expression also studied in human lung granulomas of tuberculosis patients (see Fenhalls et al., 2002). RT-PCR shows increased expression in M. tuberculosis H37Rv grown in anaerobic non-replicating conditions (See Saxena et al., 2008). |
| Mutant | Essential gene for in vitro growth of H37Rv in a MtbYM rich medium, by Himar1 transposon mutagenesis (see Minato et al. 2019). Disruption of this gene results in growth defect of H37Rv in vitro, by analysis of saturated Himar1 transposon libraries (see DeJesus et al. 2017). Essential gene for in vitro growth of H37Rv, by Himar1 transposon mutagenesis (See Griffin et al., 2011). 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 | 557527 | 558813 | + |
Genomic sequence
Feature type
Upstream flanking region (bp)
Downstream flanking region (bp)
Update
Protein sequence
>Mycobacterium tuberculosis H37Rv|Rv0467|icl1
MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQLHDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQVVRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSHWEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSDVDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEAVKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFDLAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTGSTEEGQFH
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. Product Biochemistry Function
- Graham JE and Clark-Curtiss JE [1999]. Identification of Mycobacterium tuberculosis RNAs synthesized in response to phagocytosis by human macrophages by selective capture of transcribed sequences (SCOTS). Transcriptome
- McKinney JD et al. [2000]. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Mutant Function
- Sharma V, Sharma S, Hoener zu Bentrup K, McKinney JD, Russell DG, Jacobs Jr WR and Sacchettini JC [2000]. Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Structure Function Mutant
- Fenhalls G, Stevens L, Moses L, Bezuidenhout J, Betts JC, Helden Pv P, Lukey PT and Duncan K [2002]. In situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression in necrotic lesions. Transcriptome Regulation
- Fisher MA, Plikaytis BB and Shinnick TM [2002]. Microarray analysis of the Mycobacterium tuberculosis transcriptional response to the acidic conditions found in phagosomes. Transcriptome Regulation
- Dubnau E et al. [2002]. Mycobacterium tuberculosis genes induced during infection of human macrophages. Transcriptome
- Mattow J, Schaible UE, Schmidt F, Hagens K, Siejak F, Brestrich G, Haeselbarth G, Muller EC, Jungblut PR and Kaufmann SH [2003]. Comparative proteome analysis of culture supernatant proteins from virulent Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen. Proteomics
- Muñoz-Elías EJ et al. [2005]. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Mutant
- Mawuenyega KG et al. [2005]. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Proteomics
- 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
- Gould TA et al. [2006]. Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in Mycobacterium tuberculosis. Function Structure
- Saxena A et al. [2008]. Identification of genes of Mycobacterium tuberculosis upregulated during anaerobic persistence by fluorescence and kanamycin resistance selection. Transcriptome
- Zvi A et al. [2008]. Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses. Immunology
- Griffin JE et al. [2011]. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. Mutant
- de Souza GA et al. [2011]. Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. Proteomics
- 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
