citE Family assigned · medium auto-curated

H37Rv Rv2498c · MTBC0 mtbc0_002660 · 273 aa · 2835245–2836066 (-) · RefSeq NP_217014.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)citrate (pro-3S)-lyase subunit beta
MTBC0 PGAP re-annotationcitrate (pro-3S)-lyase subunit beta
Revised (this work)Citrate (pro-3S)-lyase subunit beta. Pfam: HpcH_HpaI (PF03328.21), C-C_Bond_Lyase (PF15617.13).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WPE1 SwissProt · reviewed · Evidence at protein level
UniProt nameCitrate lyase subunit beta-like protein
EC (curated) EC 4.1.-.-
Curated functionMay play a role in fatty acid biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namecitE
eggNOG descriptionBelongs to the HpcH HpaI aldolase family
Orthologous groupCOG2301
EC number EC 4.1.3.34
KEGG orthology K01644
KEGG pathways map02020
Gene Ontology (17) GO:0000287, GO:0003674, GO:0005488, GO:0006082, GO:0006107, GO:0008150, GO:0008152, GO:0009987, GO:0019752, GO:0043167, GO:0043169, GO:0043436 +5 more

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 0.238 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 4 missense, 0 nonsense, 0 frameshift

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)

PfamAccessioni-EvalueResiduesDescription
HpcH_HpaIPF03328.21 9.7e-2811–211 HpcH/HpaI aldolase/citrate lyase
C-C_Bond_LyasePF15617.13 8.1e-07187–267 C-C_Bond_Lyase of the TIM-Barrel fold

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv2499c (oxidase regulatory-like protein), high confidence from genomic context alone (score 993 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2499c oxidase regulatory-like protein 998 993 ctx neighborhood:882 cooccurence:760 coexpression:761 textmining:816
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 990 981 ctx neighborhood:881 coexpression:826 textmining:528
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 995 977 ctx neighborhood:881 coexpression:787 textmining:830
Rv3075c hyp hypothetical protein 949 926 database:900
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 991 907 ctx neighborhood:881 textmining:916
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 945 886 ctx neighborhood:881 textmining:540
Rv2504c scoA succinyl-CoA:3-ketoacid-CoA transferase subunit A 987 885 ctx neighborhood:881 textmining:899
Rv2506 TetR family transcriptional regulator 918 776 ctx neighborhood:714 textmining:651
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 887 770 ctx neighborhood:723 textmining:533
Rv2497c bkdA 3-methyl-2-oxobutanoate dehydrogenase subunit alpha 840 740 ctx neighborhood:724 textmining:411
Rv2496c bkdB 3-methyl-2-oxobutanoate dehydrogenase subunit beta 746 737 ctx neighborhood:723
Rv0727c fucA L-fuculose phosphate aldolase FucA 731 732 coexpression:732
Rv2505c fadD35 fatty-acid--CoA ligase FadD35 850 568 ctx neighborhood:567 textmining:667
Rv1130 prpD 2-methylcitrate dehydratase 543 524
Rv0216 hydratase 524 501 ctx fusion:401

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 (pro-3S)-lyase subunit beta
  • MTBC0 PGAP product: citrate (pro-3S)-lyase subunit beta
  • Pfam (hmmscan --cut_ga): HpcH_HpaI PF03328.21 (E=1e-27), C-C_Bond_Lyase PF15617.13 (E=8e-07)
  • (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_217014.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HpcH_HpaI (PF03328.21), C-C_Bond_Lyase (PF15617.13)
  • 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 COG2301
  • Curated reference: UniProt P9WPE1 (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 — 31 functional partner(s); context anchor Rv2499c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002660|Rv2498c|citE
MNLRAAGPGWLFCPADRPERFAKAAAAADVVILDLEDGVAEAQKPAARNALRDTPLDPERTVVRINAGGTADQARDLEALAGTAYTTVMLPKAESAAQVIELAPRDVIALVETARGAVCAAEIAAADPTVGMMWGAEDLIATLGGSSSRRADGAYRDVARHVRSTILLAASAFGRLALDAVHLDILDVEGLQEEARDAAAVGFDVTVCIHPSQIPVVRKAYRPSHEKLAWARRVLAASRSERGAFAFEGQMVDSPVLTHAETMLRRAGEATSE