Rv3194c Family assigned · medium auto-curated

H37Rv Rv3194c · MTBC0 mtbc0_003395 · 340 aa · 3585396–3586418 (-) · RefSeq NP_217710.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationPDZ domain-containing protein
Revised (this work)PDZ domain-containing protein. Pfam: PDZ_2 (PF13180.13), Lon_C (PF05362.20).

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

Curated reference (UniProt)

UniProt O53340 TrEMBL · unreviewed · Evidence at protein level
UniProt nameendopeptidase La
EC (curated) EC 3.4.21.53

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred namelon
eggNOG descriptionBelongs to the peptidase S16 family
Orthologous groupCOG3480
KEGG orthology K07177
KEGG pathways map02024

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 1.031 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
PDZ_2PF13180.13 8.3e-10135–193 PDZ domain
Lon_CPF05362.20 1.7e-08236–305 Lon protease (S16) C-terminal proteolytic domain

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

Closest characterised functional partner: Rv3193c (transmembrane protein), high confidence from genomic context alone (score 803 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3195 hyp hypothetical protein 837 838 ctx neighborhood:784
Rv3193c transmembrane protein 804 803 ctx neighborhood:778
Rv3196 hyp hypothetical protein 567 566 ctx neighborhood:566
Rv2145c wag31 cell wall synthesis protein Wag31 536 536 ctx cooccurence:521
Rv1423 whiA transcriptional regulator WhiA 527 527 ctx cooccurence:527
Rv3219 whiB1 transcriptional regulator WhiB1 530 430 ctx cooccurence:430
Rv2413c hyp hypothetical protein 416 416
Rv3260c whiB2 transcriptional regulator WhiB2 640 414 ctx cooccurence:414 textmining:411
Rv1830 HTH-type transcriptional regulator 413 413 ctx cooccurence:413
Rv2147c sepF cell division protein SepF 404 404 ctx cooccurence:404
Rv2965c kdtB phosphopantetheine adenylyltransferase 400 363
Rv2175c DNA-binding protein 516 260
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 411 45 textmining:409
Rv0814c sseC2 hyp hypothetical protein 656 41 textmining:656
Rv2672 protease 541 41 textmining:541

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: PDZ domain-containing protein
  • Pfam (hmmscan --cut_ga): PDZ_2 PF13180.13 (E=8e-10), Lon_C PF05362.20 (E=2e-08)
  • (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_217710.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PDZ_2 (PF13180.13), Lon_C (PF05362.20)
  • 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 COG3480
  • Curated reference: UniProt O53340 (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 — 20 functional partner(s); context anchor Rv3193c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003395|Rv3194c|
MNRRILTLMVALVPIVVFGVLLAVVTVPFVALGPGPTFDTLGEIDGKQVVQIVGTQTYPTSGHLNMTTVSQRDGLTLGEALALWLSGQEQLMPRDLVYPPGKSREEIENDNAADFKRSEAAAEYAALGYLKYPKAVTVASVMDPGPSVDKLQAGDAIDAVDGTPVGNLDQFTALLKNTKPGQEVTIDFRRKNEPPGIAQITLGKNKDRDQGVLGIEVVDAPWAPFAVDFHLANVGGPSAGLMFSLAVVDKLTSGHLVGSTFVAGTGTIAVDGKVGQIGGITHKMAAARAAGATVFLVPAKNCYEASSDSPPGLKLVKVETLSQAVDALHAMTSGSPTPSC