Rv1998c Family assigned · medium auto-curated

H37Rv Rv1998c · MTBC0 mtbc0_002125 · 258 aa · 2266558–2267334 (-) · RefSeq NP_216514.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationisocitrate lyase/phosphoenolpyruvate mutase family protein
Revised (this work)Isocitrate lyase/phosphoenolpyruvate mutase family protein. Pfam: PEP_mutase (PF13714.13).

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

Curated reference (UniProt)

UniProt P9WLN9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1998c

UniProt still lists this protein as Uncharacterized protein Rv1998c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionPhosphoenolpyruvate phosphomutase
Orthologous groupCOG2513

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 0.135 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 2 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
PEP_mutasePF13714.13 8.9e-693–229 Phosphoenolpyruvate phosphomutase

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

Closest characterised functional partner: Rv1999c (transporter), medium confidence from genomic context alone (score 637 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3195 hyp hypothetical protein 767 768 coexpression:768
Rv0819 mshD mycothiol acetyltransferase 767 768 coexpression:768
Rv1130 prpD 2-methylcitrate dehydratase 804 744 coexpression:723
Rv3470c ilvB2 acetolactate synthase large subunit 741 725 coexpression:716
Rv0896 gltA2 citrate synthase 1 750 724 coexpression:674
Rv1131 prpC methylcitrate synthase PrpC 749 723 coexpression:673
Rv0889c citA citrate synthase 2 749 723 coexpression:673
Rv1999c transporter 636 637 ctx neighborhood:583
Rv1317c alkA bifunctional regulatory protein/DNA repair enzyme AlkA 546 546 ctx cooccurence:404
Rv1837c glcB malate synthase 623 509 coexpression:508
Rv3667 acs acetyl-CoAsynthetase 622 508 coexpression:467
Rv1240 mdh malate dehydrogenase 595 472
Rv0250c hyp hypothetical protein 464 464 ctx neighborhood:461
Rv2781c oxidoreductase 447 447
Rv1234 transmembrane protein 443 444 coexpression:444

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: hypothetical protein
  • MTBC0 PGAP product: isocitrate lyase/phosphoenolpyruvate mutase family protein
  • Pfam (hmmscan --cut_ga): PEP_mutase PF13714.13 (E=9e-69)
  • (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_216514.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PEP_mutase (PF13714.13)
  • 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 COG2513
  • Curated reference: UniProt P9WLN9 (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 — 26 functional partner(s); context anchor Rv1999c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002125|Rv1998c|
MSFHDLHHQGVPFVLPNAWDVPSALAYLAEGFTAIGTTSFGVSSSGGHPDGHRATRGANIALAAALAPLQCYVSVDIEDGYSDEPDAIADYVAQLSTAGINIEDSSAEKLIDPALAAAKIVAIKQRNPEVFVNARVDTYWLRQHADTTSTIQRALRYVDAGADGVFVPLANDPDELAELTRNIPCPVNTLPVPGLTIADLGELGVARVSTGSVPYSAGLYAAAHAARAVRDGEQLPRSVPYAELQARLVDYENRTSTT