Rv0625c Family assigned · medium auto-curated

H37Rv Rv0625c · MTBC0 mtbc0_000658 · 246 aa · 720706–721446 (-) · RefSeq NP_215139.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationTVP38/TMEM64 family protein
Revised (this work)TVP38/TMEM64 family protein. Pfam: VTT_dom (PF09335.17).

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

Curated reference (UniProt)

UniProt P9WFS5 SwissProt · reviewed · Evidence at protein level
UniProt nameTVP38/TMEM64 family membrane protein Rv0625c

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPFAM SNARE associated Golgi protein
Orthologous groupCOG0398

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 0.079 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.63% of strains (915) · 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
VTT_domPF09335.17 1.1e-1771–188 VTT domain

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

Closest characterised functional partner: vapB5 (antitoxin VapB5), medium confidence from genomic context alone (score 582 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0626 vapB5 antitoxin VapB5 582 582 ctx neighborhood:579
Rv0627 vapC5 ribonuclease VapC5 581 580 ctx neighborhood:579
Rv1978 hyp hypothetical protein 551 552 ctx cooccurence:543
Rv3882c eccE1 ESX-1 secretion system protein EccE1 519 520 ctx cooccurence:519
Rv3877 eccD1 ESX-1 secretion system protein EccD1 487 488 ctx cooccurence:486
Rv2633c hyp hypothetical protein 474 474 ctx cooccurence:464
Rv3875 esxA ESAT-6 protein EsxA 419 420 ctx cooccurence:418
Rv2687c antibiotic ABC transporter permease 433 412 ctx cooccurence:411
Rv1355c moeY molybdopterin biosynthesis protein MoeY 401 401 ctx cooccurence:401
Rv2181 alpha-(1-2)-phosphatidylinositol mannoside mannosyltransferase 603 397
Rv0204c transmembrane protein 620 333 textmining:455
Rv3483c hyp hypothetical protein 670 147 textmining:630
Rv2182c 1-acylglycerol-3-phosphate O-acyltransferase 506 142 textmining:448
Rv1337 integral membrane protein 668 140 textmining:630
Rv1275 lprC lipoprotein LprC 625 78 textmining:611

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: transmembrane protein
  • MTBC0 PGAP product: TVP38/TMEM64 family protein
  • Pfam (hmmscan --cut_ga): VTT_dom PF09335.17 (E=1e-17)
  • (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_215139.1)
  • Domains: Pfam-A via hmmscan --cut_ga — VTT_dom (PF09335.17)
  • 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 COG0398
  • Curated reference: UniProt P9WFS5 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 25 functional partner(s); context anchor vapB5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000658|Rv0625c|
MSTHNDSAPTSRRRHIVRLVVFAGFLVGMFYLVAATDVIDVAAVRGAVSATGPAAPLTYVVVSAVLGALFVPGPILAASSGLLFGPLVGVFVTLGATVGTAVVASLVGRRAGRASARALLGGERADRTDALIERCGLWAVVGQRFVPGISDAFASYAFGTFGVPLWQMAVGAFIGSAPRAFAYTALGAAIGDRSPLLASCAIAVWCVTAIIGAFAARHGYRQWRAHARGDGADGGVEDPDREVGAR