Rv3005c Family assigned · medium auto-curated

H37Rv Rv3005c · MTBC0 mtbc0_003194 · 279 aa · 3385002–3385841 (-) · RefSeq NP_217521.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDoxX family protein
Revised (this work)DoxX family protein. Pfam: DoxX (PF07681.18), MauE (PF07291.17).

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

Curated reference (UniProt)

UniProt I6YAV3 TrEMBL · unreviewed · Evidence at protein level
UniProt nameDoxX family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionmembrane
Orthologous groupCOG2259
KEGG orthology K15977

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 0.121 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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
DoxXPF07681.18 4.6e-20114–194 DoxX
MauEPF07291.17 5.5e-07115–194 Methylamine utilisation protein MauE

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

Closest characterised functional partner: lppZ (lipoprotein LppZ), medium confidence from genomic context alone (score 563 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0435c ATPase 585 586 database:576
Rv3868 eccA1 ESX-1 secretion system protein EccA1 580 581 database:576
Rv3884c eccA2 ESX-2 secretion system protein EccA 579 580 database:576
Rv0282 eccA3 ESX-3 secretion system protein EccA 578 579 database:576
Rv3006 lppZ lipoprotein LppZ 563 563 ctx neighborhood:557
Rv0425c ctpH metal cation transporting ATPase H 495 495
Rv0908 ctpE metal cation transporter ATPase E 485 485
Rv0107c ctpI cation-transporter ATPase I 483 483
Rv1997 ctpF cation transporter ATPase F 482 483
Rv1305 atpE ATP synthase subunit C 441 441 database:417
Rv0412c glnX membrane protein 434 435 ctx cooccurence:421
Rv3414c sigD ECF RNA polymerase sigma factor SigD 430 420
Rv0732 secY preprotein translocase SecY 406 369
Rv3492c Mce associated protein 400 274
Rv2704 hyp hypothetical protein 454 223

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: DoxX family protein
  • Pfam (hmmscan --cut_ga): DoxX PF07681.18 (E=5e-20), MauE PF07291.17 (E=6e-07)
  • (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_217521.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DoxX (PF07681.18), MauE (PF07291.17)
  • 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 COG2259
  • Curated reference: UniProt I6YAV3 (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 — 24 functional partner(s); context anchor lppZ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003194|Rv3005c|
MTSSNDSHWQRPDDSPGPMPGRPVSASLVDPEDDLTPARYAGDFGSGTTTVIPPYDAASSGVGNSGYSLIEAAEPLPYVQPQPGRQVPAGSAGIDMDDDERVRAAGRRGTQNLGLLILRVGLGAVLIAHGLQKLFGWWDGQGLAGFQNSLSDIGYQHAEILAYVSAGGEIVAGVLLVLGLFTPLAAAGALAFLINGLLAGISAQHSRPVAYFLQDGHEYQITLVVMAVAVILSGPGRYGLDAARGWAHRPFIGSFVALLGGIAAGIAVWVLLNGANPLA