Rv2425c Family assigned · medium auto-curated

H37Rv Rv2425c · MTBC0 mtbc0_002582 · 480 aa · 2746134–2747576 (-) · RefSeq NP_216941.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationVWA domain-containing protein
Revised (this work)VWA domain-containing protein. Pfam: VWA_CoxE (PF05762.21).

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

Curated reference (UniProt)

UniProt P71923 TrEMBL · unreviewed · Evidence at protein level
UniProt nameVWA domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein containing von Willebrand factor type A (VWA) domain
Orthologous groupCOG3552
KEGG orthology K07161

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 0.953 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (343) · 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
VWA_CoxEPF05762.21 5.3e-67252–473 VWA domain containing CoxE-like protein

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

Closest characterised functional partner: proA (gamma-glutamyl phosphate reductase), high confidence from genomic context alone (score 822 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2426c hyp hypothetical protein 976 976 ctx neighborhood:882 cooccurence:771
Rv2427c proA gamma-glutamyl phosphate reductase 822 822 ctx neighborhood:817
Rv0370c oxidoreductase 762 759 ctx cooccurence:728
Rv2417c DegV domain-containing protein 606 606 ctx neighborhood:544
Rv0696 mftF mycofactocin biosynthesis glycosyltransferase MftF 605 606 ctx cooccurence:582
Rv2424c transposase 566 566 ctx neighborhood:561
Rv0693 mftC mycofactocin radical SAM maturase MftC 553 554 ctx cooccurence:536
Rv2418c octT hyp hypothetical protein 546 547 ctx neighborhood:544
Rv2420c rsfS hyp hypothetical protein 544 544 ctx neighborhood:544
Rv2421c nadD nicotinate-nucleotide adenylyltransferase 544 544 ctx neighborhood:544
Rv0368c hyp hypothetical protein 520 521 ctx cooccurence:518
Rv0692 mftB mycofactocin system protein MftB 499 500 ctx cooccurence:464
Rv2427A oxyR Rv2427A, Pseudogene oxyR', inactivated by multiple mutations; identical to sequence in u16243 (see Deretic et al., 1995). 445 445 ctx neighborhood:445
Rv0207c hyp hypothetical protein 437 438 ctx cooccurence:434
Rv2453c mobA molybdenum cofactor guanylyltransferase 837 179 textmining:810

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: VWA domain-containing protein
  • Pfam (hmmscan --cut_ga): VWA_CoxE PF05762.21 (E=5e-67)
  • (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_216941.1)
  • Domains: Pfam-A via hmmscan --cut_ga — VWA_CoxE (PF05762.21)
  • 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 COG3552
  • Curated reference: UniProt P71923 (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 — 18 functional partner(s); context anchor proA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002582|Rv2425c|
MAARRIRAARPLAPHGLPGHLVGFVEALRGSGISVGPSETVDAGRVMATLGLGDREVLREGIACAVLRRPDHRDTYDAMFDLWFPAALGARAVITTEDESAGSGGLPPDDVEAMRQLLLDLLANNQDLAGKDERLVEMIARIVEAYGKYSSSRGPSFSSYQALKAMALDELEGKLLAGLLAPYGDEPTATQEQIAKALAAQKIAQLRRMVDAETKRRTAEQLGREHVQMYGIPQLSENVEFLRASGEQLRQMRRVVAPLARTLATRLAARRRRARAGSIDLRKTLRKSMSTGGVPIDLVLHKPRPARPELVVLCDVSGSVAGFSHFTLLLVHALRQQFSRVRVFAFIDSTDEVTHMFGPESDLAIAIQRITREAGVYARDGHSDYGNAFVSFMQGFPNVLSPRSSLLVLGDGRTNYRNPATDVLADMVTASRHAHWLNPEPKHLWGSGDSAVPRYQEVITMHECRSAKQLATVIDQLLPV