Rv1825 Still unknown · low auto-curated

H37Rv Rv1825 · MTBC0 mtbc0_001939 · 292 aa · 2089124–2090002 (+) · RefSeq NP_216341.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF881 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF881. Function unknown. Foldseek best (non-significant) hit: 3gmg-assembly1_B Crystal structure of an uncharacterized conserved pro (prob 1.00, TM 0.93).

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

Curated reference (UniProt)

UniProt P9WFG3 SwissProt · reviewed · Evidence at protein level
UniProt nameUPF0749 protein Rv1825

UniProt still lists this protein as UPF0749 protein Rv1825; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionBacterial protein of unknown function (DUF881)
Orthologous groupCOG3879
Gene Ontology (13) GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0044425, GO:0044459, GO:0044464 +1 more

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 1.471 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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
DUF881PF05949.18 1.5e-34151–289 Bacterial protein of unknown function (DUF881)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 86.4 (confident). A confident model makes the fold comparison meaningful.

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
3gmg-assembly1_B 1.00 0.93 1.7e-28 sig 3gmg-assembly1_B Crystal structure of an uncharacterized conserved protein from Mycobacterium tuberculosis
7jts-assembly1_s 0.07 0.24 5.4e+00 7jts-assembly1_s Stalk of radial spoke 1 attached with doublet microtubule from Chlamydomonas reinhardtii
3jcm-assembly1_K 0.06 0.20 1.8e+00 3jcm-assembly1_K Cryo-EM structure of the spliceosomal U4/U6.U5 tri-snRNP
7ju4-assembly1_F 0.04 0.22 8.4e+00 7ju4-assembly1_F Radial spoke 2 stalk, IDAc, and N-DRC attached with doublet microtubule
8h6l-assembly1_4B 0.04 0.20 2.4e+00 8h6l-assembly1_4B Cryo-EM structure of human exon-defined spliceosome in the early B state.

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

Closest characterised functional partner: gcvH (glycine cleavage system protein H), high confidence from genomic context alone (score 835 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1824 hyp hypothetical protein 979 978 ctx neighborhood:861 cooccurence:774
Rv1823 hyp hypothetical protein 921 882 ctx neighborhood:822
Rv1826 gcvH glycine cleavage system protein H 835 835 ctx neighborhood:826
Rv1822 pgsA2 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 824 825 ctx neighborhood:822
Rv0012 membrane protein 774 775 ctx cooccurence:774
Rv1821 secA2 accessory Sec system translocase SecA2 708 708 ctx neighborhood:705
Rv1820 ilvG acetolactate synthase large subunit IlvG 698 699 ctx neighborhood:699
Rv1827 garA glycogen accumulation regulator GarA 658 658 ctx neighborhood:653
Rv1819c bacA vitamin B12 transport ATP-binding protein BacA 601 602 ctx neighborhood:599
Rv1828 HTH-type transcriptional regulator 556 556 ctx neighborhood:536
Rv1829 hyp hypothetical protein 925 451 ctx neighborhood:442 textmining:870
Rv1009 rpfB resuscitation-promoting factor RpfB 408 409
Rv3586 disA DNA integrity scanning protein DisA 405 406 ctx cooccurence:404
Rv2612c pgsA1 CDP-diacylglycerol--inositol 3-phosphatidyltransferase 831 178 textmining:803
Rv2746c pgsA3 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 874 77 textmining:870

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: DUF881 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF881 PF05949.18 (E=1e-34)
  • Foldseek best: 3gmg-assembly1_B Crystal structure of an uncharacterized conserved protein from (prob 1.00, E=2e-28, TM=0.93)
  • (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_216341.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF881 (PF05949.18)
  • 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 COG3879
  • Curated reference: UniProt P9WFG3 (SwissProt, reviewed; 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)
  • Model confidence: ESMFold per-residue pLDDT (mean 86.4, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 17 functional partner(s); context anchor gcvH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001939|Rv1825|
MSENRPEPVAAETSAATTARHSQADAGAHDAVRRGRHELPADHPRSKVGPLRRTRLTEILRGGRSRLVFGTLAILLCLVLGVAIVTQVRQTDSGDSLETARPADLLVLLDSLRQREATLNAEVIDLQNTLNALQASGNTDQAALESAQARLAALSILVGAVGATGPGVMITIDDPGPGVAPEVMIDVINELRAAGAEAIQINDAHRSVRVGVDTWVVGVPGSLTVDTKVLSPPYSILAIGDPPTLAAAMNIPGGAQDGVKRVGGRMVVQQADRVDVTALRQPKQHQYAQPVK