Rv0193c Family assigned · low

H37Rv Rv0193c · MTBC0 mtbc0_000207 · 615 aa · 225073–226920 (-) · RefSeq NP_214707.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Putative 2-oxoglutarate / Fe(II)-dependent oxygenase. No Pfam domain above threshold, but Foldseek gives a significant match to a proline-hydroxylase (2OG-Fe(II) oxygenase) fold (prob 1.00, E=1e-4, TM=0.57). Structure-based hypothesis.

Curated reference (UniProt)

UniProt O07437 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2EIH2

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 0.644 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 9 synonymous, 18 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)

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

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 57.0 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
7e08-assembly1_A-2 1.00 0.57 1.0e-04 sig 7e08-assembly1_A-2 Trans-3/4-proline-hydroxylase H11 with 4-Hydroxyl-proline
7e01-assembly1_A-2 1.00 0.57 7.9e-05 sig 7e01-assembly1_A-2 Trans-3/4-proline-hydroxylase H11 in the sixth reaction state
8h7v-assembly2_B 1.00 0.59 1.2e-04 sig 8h7v-assembly2_B Trans-3/4-proline-hydroxylase H11 with AKG
4nmi-assembly1_A-2 1.00 0.54 3.2e-05 sig 4nmi-assembly1_A-2 Crystal Structure of the Apo ectoine hydroxylase ECTD from Salibacillus salexigens
7dt0-assembly3_C 1.00 0.61 1.9e-04 sig 7dt0-assembly3_C Proline hydroxylase H11-N101I mutant
8h7y-assembly1_A 1.00 0.56 1.5e-04 sig 8h7y-assembly1_A Trans-3/4-proline-hydroxylase H11 with AKG and L-proline
8h7t-assembly1_A 1.00 0.55 1.5e-04 sig 8h7t-assembly1_A Trans-3/4-proline-hydroxylase H11 apo structure
8h85-assembly1_A 1.00 0.58 2.2e-04 sig 8h85-assembly1_A Trans-3/4-proline-hydroxylase H11 with 3-hydroxyl-proline

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0194 multidrug ABC transporter ATPase/permease 955 877 coexpression:804 textmining:653
Rv1675c cmr HTH-type transcriptional regulator Cmr 783 783 coexpression:783
Rv1190 hyp hypothetical protein 774 774 coexpression:774
Rv3124 moaR1 transcriptional regulator MoaR 761 761 coexpression:761
Rv1189 sigI ECF RNA polymerase sigma factor SigI 740 740 coexpression:740
Rv3114 hyp hypothetical protein 734 734 coexpression:734
Rv0195 two component transcriptional regulator 903 732 coexpression:731 textmining:655
Rv0603 hyp hypothetical protein 731 731 coexpression:731
Rv3111 moaC1 cyclic pyranopterin monophosphate synthase accessory protein 731 731 coexpression:731
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 730 730 coexpression:730
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 493 494 coexpression:494
Rv0602c tcrA two component DNA binding transcriptional regulator TcrA 431 431 coexpression:431
Rv3113 phosphatase 422 423 coexpression:423
Rv3110 moaB1 pterin-4-alpha-carbinolamine dehydratase 408 409 coexpression:409
Rv3167c TetR family transcriptional regulator 404 404 coexpression:404

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

  • MTBC0 PGAP product: 'hypothetical protein'
  • Pfam: none above threshold
  • Foldseek on the ESMFold model: significant match to a trans-proline-hydroxylase / 2OG-Fe(II) oxygenase fold (E=1e-4, TM=0.57)

ESM Atlas signal (exploratory)

Ancestral protein hash 196253476cc84faed042be27667dd710 · 10 ESM-space neighbours (max similarity 0.823). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
12447 1.27 DSBH Fe(II)/2OG oxygenase core
22751 1.26 Fe(II)/2OG oxygenase catalytic core
313210 1.16 2OG oxygenase jelly-roll core
413087 1.15 DSBH 2OG oxygenase active-site lid
515298 1.13 2OG oxygenase N-terminal activation
65522 1.05 2OG oxygenase HxD/E core
711797 1.04 2OG oxygenase N-terminal cap
811638 1.02 Fe/2OG oxygenase active site

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_214707.1)
  • 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 2EIH2
  • Curated reference: UniProt O07437 (TrEMBL, unreviewed; Predicted)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Model confidence: ESMFold per-residue pLDDT (mean 57.0, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 19 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000207|Rv0193c|
MIQISRDMSSLGQTATTQALPDNSDGIQLTKFAADDILPLEYAPPIGPELVSQDQLPAAWAYKRFRDLDDKESYRRKLLQELTDALAAQGSEAAEIATAALRDLIDQMAEQGAVVLADIVESDDFLELVKRYDELMAREGSRSFIHRFLDLRRSPGMLTDPAVNGALVHPLMIALISYAVGGPIRMIDARGKDAEPLSVLAQDNMLHIDNTPFNDEYKILITWRRGTAQGPAGQNFTFLPGTHKLARTCFVNEDGVPWSSENASIFTTPDSIRKVFDAQRQLGGQDHPTVIEVTDSERPLSSVFAAGSLVHHRFRTASGSARSCIILVFHRVADNPGRMVSDVEDSSDVSLSELLTRGVPDESYQQRFIATLCAAADEIAELLLKWKKTPQRPVSLPLQTKQIDGARFEEWISAATEAPEVREIRNRELTIPYGEVLSAEEFFDLIWRLMRFDKHGPLDLILYHDNREEPRKWARNLIREMSADRLYERLLGWLADIQQPRPADCLRPLQIHALISEVLKTLPLDEDQDPPADWHFDLLGMSHAEAARSVKHLLEDVAEALLRCEDMAAYLSTSLFAFWAVDAAYSLDGRRNLVVKDCARRLLRHYTMLSLTCFQ