Rv0332 Family assigned · medium auto-curated

H37Rv Rv0332 · MTBC0 - · 261 aa · 397442–398227 (+) · RefSeq NP_214846.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains MDMPI_N (PF11716.14), MDMPI_C (PF07398.17) domain(s); putative function inferred from the domain architecture.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O07256 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionMDMPI C-terminal domain
Orthologous groupCOG3550

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 0.441 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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
MDMPI_NPF11716.14 1.5e-2520–140 Mycothiol maleylpyruvate isomerase N-terminal domain
MDMPI_CPF07398.17 1.6e-17153–253 MDMPI C-terminal domain

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

Closest characterised functional partner: rmlA (glucose-1-phosphate thymidylyltransferase), high confidence from genomic context alone (score 811 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2515c hyp hypothetical protein 936 927 experimental:916
Rv0333 hyp hypothetical protein 869 870 ctx neighborhood:843
Rv0334 rmlA glucose-1-phosphate thymidylyltransferase 818 811 ctx neighborhood:805
Rv0331 dehydrogenase/reductase 588 589 ctx neighborhood:589
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 545 545 ctx neighborhood:544
Rv2483c plsC bifunctional L-3-phosphoserine phosphatase/1-acyl-sn-glycerol-3-phosphate acyltransferase 536 536 ctx cooccurence:533
Rv0941c hyp hypothetical protein 522 523 ctx cooccurence:518
Rv2017 transcriptional regulator 541 517 experimental:434
Rv3183 higA3 transcriptional regulator 525 500 experimental:434
Rv0465c ramB HTH-type transcriptional regulator 523 497 experimental:434
Rv2021c higA2 transcriptional regulator 520 494 experimental:434
Rv0474 HTH-type transcriptional regulator 515 489 experimental:434
Rv2745c clgR transcriptional regulator ClgR 507 480 experimental:434
Rv1129c prpR transcriptional regulator 506 479 experimental:434
Rv3849 espR ESX-1 transcriptional regulator EspR 504 477 experimental:434

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): MDMPI_N PF11716.14 (E=1e-25), MDMPI_C PF07398.17 (E=2e-17)
  • (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_214846.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MDMPI_N (PF11716.14), MDMPI_C (PF07398.17)
  • 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 COG3550
  • Curated reference: UniProt O07256 (TrEMBL, unreviewed; 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 — 21 functional partner(s); context anchor rmlA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0332|
MRKPASSLAKVDYSSAYLEQTHAFGELIRNVDQSTPVPTCPGWSLGQLFRHVGRGDRWAAQIVRDRLDHFLDPRSVEGGKPPPDPDDAISWLYGGARLLVDAVEQTGVETPVWTFLGPRPAGWWVRRRLHEVAVHRADVAITVGGEFTLEPNVAADGISEFLERIAVQAGSGGTPLPLEDDDTLHLHATDPGLLEAGEWTVRRDERGVTWSHRHGKGAVALRGGATELLLAMVRRLSVADTGIELLGDAGVWQKWLDRTPL