Rv0576 Family assigned · medium auto-curated

H37Rv Rv0576 · MTBC0 mtbc0_000606 · 434 aa · 673399–674703 (+) · RefSeq NP_215090.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator
MTBC0 PGAP re-annotationTIGR03086 family metal-binding protein
Revised (this work)TIGR03086 family metal-binding protein. Pfam: HTH_20 (PF12840.14), HTH_5 (PF01022.27), Polyketide_cyc2 (PF10604.16), AHSA1 (PF08327.18).

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

Curated reference (UniProt)

UniProt O53773 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG0640

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 0.92 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (242) · 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)

PfamAccessioni-EvalueResiduesDescription
HTH_20PF12840.14 7.4e-126–52 Helix-turn-helix domain
HTH_5PF01022.27 7.0e-138–52 Bacterial regulatory protein, arsR family
Polyketide_cyc2PF10604.16 1.9e-08105–203 Polyketide cyclase / dehydrase and lipid transport
AHSA1PF08327.18 7.9e-28115–228 Activator of Hsp90 ATPase homolog 1-like protein

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

Closest characterised functional partner: Rv0575c (oxidoreductase), medium confidence from genomic context alone (score 561 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0577 TB27.3 hyp hypothetical protein 767 767 ctx neighborhood:755
Rv0575c oxidoreductase 561 561 ctx neighborhood:552
Rv1189 sigI ECF RNA polymerase sigma factor SigI 526 524 ctx cooccurence:492
Rv2640c ArsR family transcriptional regulator 505 505 ctx cooccurence:458
Rv2487c PE_PGRS42 PE-PGRS family protein PE_PGRS42 492 492 ctx cooccurence:492
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 473 474 ctx cooccurence:450
Rv1725c hyp hypothetical protein 450 449
Rv2305 hyp hypothetical protein 430 431 ctx cooccurence:428
Rv1931c transcriptional regulator 423 423
Rv3328c sigJ ECF RNA polymerase sigma factor SigJ 419 416
Rv2643 arsC arsenic-transport integral membrane protein ArsC 411 323

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: transcriptional regulator
  • MTBC0 PGAP product: TIGR03086 family metal-binding protein
  • Pfam (hmmscan --cut_ga): HTH_20 PF12840.14 (E=7e-12), HTH_5 PF01022.27 (E=7e-13), Polyketide_cyc2 PF10604.16 (E=2e-08), AHSA1 PF08327.18 (E=8e-28)
  • (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_215090.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HTH_20 (PF12840.14), HTH_5 (PF01022.27), Polyketide_cyc2 (PF10604.16), AHSA1 (PF08327.18)
  • 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 COG0640
  • Curated reference: UniProt O53773 (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 — 11 functional partner(s); context anchor Rv0575c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000606|Rv0576|
MLEVAAEPTRRRLLQLLAPGERTVTQLASQFTVTRSAISQHLGMLAEAGLVTARKQGRERYYRLDERGVLRLRALMESFWSDELDRLVADAAHYPPSQGDCAMPFEKAVVVPLDPTSTFALITQPDRLRRWMAVAARIELRTGGAYRWTVTPGHSAAGTVIDVDPGKRVVFTWGWEDHGDPPPGGSTVTITLTPVDGGTEVRLVHDGLTAQQAARHAKGWNHFLDRLVVAGQHGDAGPDEWAAAPDPLDELSCAEATLAVLQHVLRGIGASDLTRQTPCTEYDVSQLADHLLRSLAIIGAAAGAQLAPRDVDAPLETQVADAAQAVMEAWRRRGLAGTVELNSNQVPATVPVGILCLEFLVHAWDFAIATGSQVIASEPVSEYVLAVAGKVITPATRNSAGFAAPAAVGSFAPVLDRLIAFTGRQPTAGHVSAT