Rv2345 Family assigned · medium auto-curated

H37Rv Rv2345 · MTBC0 mtbc0_002497 · 660 aa · 2648571–2650553 (+) · RefSeq NP_216861.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationTPM domain-containing protein
Revised (this work)TPM domain-containing protein. Pfam: TPM_phosphatase (PF04536.21).

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

Curated reference (UniProt)

UniProt P9WFJ5 SwissProt · reviewed · Evidence at protein level
UniProt nameUPF0603 protein Rv2345
Curated functionMay play a role in septum formation.

UniProt still lists this protein as UPF0603 protein Rv2345; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionTPM domain
Orthologous groupCOG1512
Gene Ontology (14) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226, GO:0044425, GO:0044459 +2 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 0.562 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 9 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
TPM_phosphatasePF04536.21 8.2e-2036–153 TPM domain

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

Closest characterised functional partner: dgt (deoxyguanosine triphosphate triphosphohydrolase), high confidence from genomic context alone (score 787 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3043c ctaD cytochrome C oxidase cytochrome 1 787 788 experimental:783
Rv2344c dgt deoxyguanosine triphosphate triphosphohydrolase 787 787 ctx neighborhood:785
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 786 787 experimental:783
Rv2200c ctaC cytochrome C oxidase subunit II 785 785 experimental:783
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 770 771 experimental:747
Rv2199c ctaF cytochrome c oxidase polypeptide 4 750 751 experimental:747
Rv2193 ctaE cytochrome C oxidase subunit III 750 750 experimental:747
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 749 749 experimental:747
Rv2343c dnaG DNA primase 676 676 ctx neighborhood:673
Rv2876 transmembrane protein 590 591 experimental:484
Rv3244c lpqB lipoprotein LpqB 580 581 ctx cooccurence:577
Rv3584 lpqE lipoprotein LpqE 552 552 experimental:431
Rv3517 hyp hypothetical protein 524 524 ctx cooccurence:524
Rv1482c hyp hypothetical protein 511 512 ctx cooccurence:511
Rv2468A hyp hypothetical protein 502 502 experimental:484

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: TPM domain-containing protein
  • Pfam (hmmscan --cut_ga): TPM_phosphatase PF04536.21 (E=8e-20)
  • (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_216861.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TPM_phosphatase (PF04536.21)
  • 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 COG1512
  • Curated reference: UniProt P9WFJ5 (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 — 36 functional partner(s); context anchor dgt
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002497|Rv2345|
MRLVRLLGMVLTILAAGLLLGPPAGAQPPFRLSNYVTDNAGVLTSSGRTAVTAAVDRLYADRRIRLWVVYVENFSGQSALNWAQRTTRTSELGNYDALLAVATTGREYAFLVPSAMPGVSEGQVDNVRRYQIEPALHDGDYSGAAVAAANGLNRSPSSSSRVVLLVTVGIIVIVVAVLLVVMRHRNRRRRADELAAARRVDPTNVMALAAVPLQALDDLSRSMVVDVDNAVRTSTNELALAIEEFGERRTAPFTQAVNNAKAALSQAFTVRQQLDDNTPETPAQRRELLTRVIVSAAHADRELASQTEAFEKLRDLVINAPARLDLLTQQYVELTTRIGPTQQRLAELHTEFDAAAMTSIAGNVTTATERLAFADRNISAARDLADQAVSGRQAGLVDAVRAAESALGQARALLDAVDSAATDIRHAVASLPAVVADIQTGIKRANQHLQQAQQPQTGRTGDLIAARDAAARALDRARGAADPLTAFDQLTKVDADLDRLLATLAEEQATADRLNRSLEQALFTAESRVRAVSEYIDTRRGSIGPEARTRLAEAKRQLEAAHDRKSSNPTEAIAYANAASTLAAHAQSLANADVQSAQRAYTRRGGNNAGAILGGIIIGDLLSGGTRGGLGGWIPTSFGGSSNAPGSSPDGGFLGGGGRF