Rv1375 Family assigned · medium auto-curated

H37Rv Rv1375 · MTBC0 mtbc0_001476 · 439 aa · 1557176–1558495 (+) · RefSeq NP_215891.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationYcaO-like family protein
Revised (this work)YcaO-like family protein. Pfam: YcaO (PF02624.22).

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

Curated reference (UniProt)

UniProt P9WF27 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv1375

UniProt still lists this protein as Uncharacterized protein Rv1375; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionYcaO cyclodehydratase, ATP-ad Mg2+-binding
Orthologous groupCOG1944
KEGG orthology K09136

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 0.27 · purifying
Polymorphic sites (≥ 0.1% of strains) 9 synonymous, 7 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.77% of strains (1111) · 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
YcaOPF02624.22 2.2e-57115–423 YcaO cyclodehydratase, ATP-ad Mg2+-binding

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

Closest characterised functional partner: csm5 (CRISPR type III-associated RAMP protein Csm5), medium confidence from genomic context alone (score 475 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1376 hyp hypothetical protein 988 986 ctx neighborhood:882 cooccurence:774 coexpression:533
Rv1863c integral membrane protein 656 636 coexpression:623
Rv1140 integral membrane protein 654 633 coexpression:620
Rv0658c integral membrane protein 654 633 coexpression:620
Rv0804 hyp hypothetical protein 653 632 coexpression:619
Rv1747 ABC transporter ATP-binding protein/permease 631 571 coexpression:488
Rv3262 fbiB coenzyme F420:L-glutamate ligase 535 505 coexpression:476
Rv2337c hyp hypothetical protein 532 502 ctx cooccurence:484
Rv3127 hyp hypothetical protein 523 493 coexpression:476
Rv3131 NAD(P)H nitroreductase 523 493 coexpression:476
Rv3368c oxidoreductase 522 492 coexpression:475
Rv2032 acg NAD(P)H nitroreductase 522 492 coexpression:475
Rv0306 bluB oxidoreductase 520 490 coexpression:473
Rv2819c csm5 CRISPR type III-associated RAMP protein Csm5 474 475 ctx cooccurence:468
Rv1457c antibiotic ABC transporter permease 491 460 coexpression:442

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: YcaO-like family protein
  • Pfam (hmmscan --cut_ga): YcaO PF02624.22 (E=2e-57)
  • (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_215891.1)
  • Domains: Pfam-A via hmmscan --cut_ga — YcaO (PF02624.22)
  • 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 COG1944
  • Curated reference: UniProt P9WF27 (SwissProt, reviewed; 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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 26 functional partner(s); context anchor csm5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001476|Rv1375|
MTGRRLARFPAFRAGVAQDDDVGSTLSQGSTTGVLSGPNWSYWPSRVLGSADPTTIAHRHGTHRITSPDETWLALQPFLAPAGITRVADVTWLDCLGIPTVQAVRPASLTLSVSQGKAASYRAAQVSAVMESLEGWHAENVTADLWSATARDLEADLTYDPAQLRHRPGSLYHAGVKLDWMVATTLLTGRRTWVPWTAVLVNVATRDCWEPPMFEMDTTGLASGNCYDEATLHALYEVMERHSVAAAVAGETMFEVPTDDVAGSDSAHLVEMIRDAGDDVDLARIDVWDGYYCFAAELTSATLEVTFGGFGLHHDPNVALSRAITEAAQSRITAISGAREDLPSAIYHRFGRVHTYAKARKTSLRLNRARPTPWRVPDVDSLPELVASAATAVANRSGTEPLAVVCDFADACVPVVKVLAPGLVLSSASPMRTPLQEAE