Rv3683 Resolved · high auto-curated

H37Rv Rv3683 · MTBC0 mtbc0_003903 · 319 aa · 4148365–4149324 (+) · RefSeq NP_218200.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationmetallophosphoesterase
Revised (this work)Metallophosphoesterase. Pfam: Metallophos (PF00149.34), Metallophos_2 (PF12850.13).

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

Curated reference (UniProt)

UniProt I6X827 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
Preferred nameykuE
eggNOG descriptionMetallophosphoesterase
Orthologous groupCOG1408
KEGG orthology K07098

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 0.073 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 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
MetallophosPF00149.34 9.1e-1251–234 Calcineurin-like phosphoesterase
Metallophos_2PF12850.13 5.3e-0752–233 Calcineurin-like phosphoesterase superfamily domain

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

Closest characterised functional partner: Rv3684 (lyase), high confidence from genomic context alone (score 808 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3684 lyase 950 808 ctx neighborhood:799 textmining:751
Rv2256c hyp hypothetical protein 680 681 ctx cooccurence:679
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 643 643 ctx neighborhood:638
Rv2680 hyp hypothetical protein 636 637 ctx cooccurence:635
Rv0811c hyp hypothetical protein 583 584 ctx cooccurence:574
Rv1423 whiA transcriptional regulator WhiA 581 582 ctx cooccurence:575
Rv2146c transmembrane protein 572 572 ctx cooccurence:555
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 567 567 ctx neighborhood:544
Rv2413c hyp hypothetical protein 562 563 ctx cooccurence:555
Rv1002c pmt dolichyl-phosphate-mannose--protein mannosyltransferase 559 559 ctx cooccurence:558
Rv3681c whiB4 transcriptional regulator WhiB4 518 518 ctx neighborhood:416
Rv0004 hyp hypothetical protein 481 481 ctx cooccurence:481
Rv2169c transmembrane protein 479 480 ctx cooccurence:478
Rv2699c hyp hypothetical protein 462 462 ctx cooccurence:459
Rv0883c sepH hyp hypothetical protein 462 457 ctx cooccurence:449

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: metallophosphoesterase
  • Pfam (hmmscan --cut_ga): Metallophos PF00149.34 (E=9e-12), Metallophos_2 PF12850.13 (E=5e-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_218200.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Metallophos (PF00149.34), Metallophos_2 (PF12850.13)
  • 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 COG1408
  • Curated reference: UniProt I6X827 (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 — 34 functional partner(s); context anchor Rv3684
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003903|Rv3683|
MAAVLPTLIRTGAVALGSAIAGIGYAALVERNAFVLREVTMPVLTPGSTPLRVLHISDLHMLPNQHRKQAWLRELASWEPDLVVNTGDNLAHPKAVPAVVQTLSDLLSRPGVFVFGSNDYFGPRLKNPMNYLTSPDHRVRGAALPWQDLRAAFTERGWLDLTHTRREFEVAGLHIAAAGVDDPHIDRDRYDTIAGPASPAANLRLGLTHSPEPRVLDRFAADGYQLVLAGHTHGGQLCLPLYGALVTNCGLDRSRAKGASHWGANMRLHVSAGIGTSPFAPVRFCCRPEATLLTLIATPMGGRDSSSNLGRSQPTVSVR