citA Resolved · high auto-curated
H37Rv Rv0889c · MTBC0 mtbc0_000944 ·
373 aa · 991954–993075 (-) ·
RefSeq NP_215404.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | citrate synthase 2 |
|---|---|
| MTBC0 PGAP re-annotation | citrate synthase 2 |
| Revised (this work) | Citrate synthase 2. Pfam: Citrate_synt (PF00285.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPD3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative citrate synthase 2 |
| EC (curated) |
EC 2.3.3.16
|
UniProt still lists this protein as Putative citrate synthase 2; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | citA |
| eggNOG description | Belongs to the citrate synthase family |
| Orthologous group | COG0372 |
| EC number |
EC 2.3.3.1
|
| KEGG orthology |
K01647
|
| KEGG pathways |
map00020, map00630, map01100, map01110, map01120, map01130, map01200, map01210, map01230
|
| KEGG modules |
M00009, M00010, M00012, M00740
|
| Gene Ontology (8) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0044424, GO:0044444, GO:0044464
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 1.789 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 10 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.68% of strains (982) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Citrate_synt | PF00285.27 | 6.6e-87 | 11–349 | Citrate synthase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltA2 (citrate synthase 1), high confidence from genomic context alone (score 960 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1475c acn |
iron-regulated aconitate hydratase | 995 | 991 | coexpression:692 database:941 textmining:533 |
Rv1240 mdh |
malate dehydrogenase | 992 | 979 | coexpression:650 experimental:423 database:900 textmining:672 |
Rv3667 acs |
acetyl-CoAsynthetase | 971 | 969 | coexpression:649 database:900 |
Rv0896 gltA2 |
citrate synthase 1 | 963 | 960 ctx | neighborhood:493 database:900 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 961 | 955 | coexpression:424 database:900 |
Rv1837c glcB |
malate synthase | 976 | 949 | coexpression:440 database:900 textmining:565 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 985 | 945 | coexpression:912 textmining:744 |
Rv2852c mqo |
malate:quinone oxidoreductase | 946 | 941 | coexpression:417 database:900 |
Rv1131 prpC |
methylcitrate synthase PrpC | 938 | 934 | database:900 |
Rv2967c pca |
pyruvate carboxylase | 961 | 929 | database:900 textmining:486 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 952 | 907 | database:900 textmining:509 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 939 | 905 | database:900 |
Rv0211 pckA |
phosphoenolpyruvate carboxykinase | 924 | 902 | database:900 |
Rv1098c fum |
fumarate hydratase | 962 | 893 | coexpression:422 database:800 textmining:668 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase | 894 | 890 | database:800 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: citrate synthase 2
- MTBC0 PGAP product: citrate synthase 2
- Pfam (hmmscan --cut_ga): Citrate_synt PF00285.27 (E=7e-87)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215404.1)
- Domains: Pfam-A via hmmscan --cut_ga — Citrate_synt (PF00285.27)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0372 - Curated reference: UniProt P9WPD3 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
138 functional partner(s); context anchor
gltA2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000944|Rv0889c|citA MTVVPENFVPGLDGVVAFTTEIAEPDKDGGALRYRGVDIEDLVSQRVTFGDVWALLVDGNFGSGLPPAEPFPLPIHSGDVRVDVQAGLAMLAPIWGYAPLLDIDDATARQQLARASVMALSYVAQSARGIYQPAVPQRIIDECSTVTARFMTRWQGEPDPRHIEAIDAYWVSAAEHGMNASTFTARVIASTGADVAAALSGAIGAMSGPLHGGAPARVLPMLDEVERAGDARSVVKGILDRGEKLMGFGHRVYRAEDPRARVLRAAAERLGAPRYEVAVAVEQAALSELRERRPDRAIETNVEFWAAVVLDFARVPANMMPAMFTCGRTAGWCAHILEQKRLGKLVRPSAIYVGPGPRSPESVDGWERVLTTA