Rv3773c Family assigned · low auto-curated

H37Rv Rv3773c · MTBC0 mtbc0_004000 · 194 aa · 4242362–4242946 (-) · RefSeq NP_218290.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationTIGR03086 family metal-binding protein
Revised (this work)TIGR03086 family metal-binding protein.

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

Curated reference (UniProt)

UniProt P72040 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 K Transcription
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG3832

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) pseudogene candidate

pN/pS 0.208 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 13.46% of strains (19551) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: echA21 (enoyl-CoA hydratase EchA21), high confidence from genomic context alone (score 792 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3774 echA21 enoyl-CoA hydratase EchA21 792 792 ctx neighborhood:790
Rv0048c membrane protein 744 744 ctx cooccurence:744
Rv0736 rslA anti-sigma-L factor RslA 711 712 ctx cooccurence:701
Rv3779 transmembrane protein 703 703 ctx cooccurence:703
Rv3775 lipE lipase LipE 644 644 ctx neighborhood:640
Rv3435c transmembrane protein 636 636 ctx cooccurence:634
Rv3481c integral membrane protein 570 571 ctx cooccurence:568
Rv2423 hyp hypothetical protein 567 568 ctx cooccurence:565
Rv3202c adnA ATP-dependent DNA helicase 567 567 ctx cooccurence:553
Rv0738 hyp hypothetical protein 556 556 ctx cooccurence:552
Rv3830c TetR family transcriptional regulator 545 545 ctx cooccurence:534
Rv1353c HTH-type transcriptional regulator 533 534 ctx cooccurence:530
Rv0188 transmembrane protein 531 532 ctx cooccurence:525
Rv2067c hyp hypothetical protein 522 523 ctx cooccurence:516
Rv2248 hyp hypothetical protein 509 510 ctx cooccurence:507

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: TIGR03086 family metal-binding protein
  • (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_218290.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG3832
  • Curated reference: UniProt P72040 (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 — 30 functional partner(s); context anchor echA21
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004000|Rv3773c|
MPPESRPGPDSPPTDELACAEAALQVLQQVLHTIGRQDKAKQTPCPGYDVKKLTEHLLNSIMVLGGMVGAEFSLRADIDSVERLVSGAARSALDAWHRHGLEGDVSLGPGSMSAKVAVSVFSVEFLVHAWDYAVAVGSELKAADSLAEYVLELARKLIKPEERSVAGFNEPVDVPEDGGALERLIAFTGRNPAR