Rv3594 Resolved · high auto-curated

H37Rv Rv3594 · MTBC0 mtbc0_003813 · 275 aa · 4059534–4060361 (+) · RefSeq NP_218111.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationN-acetylmuramoyl-L-alanine amidase
Revised (this work)N-acetylmuramoyl-L-alanine amidase. Pfam: Amidase_2 (PF01510.31), Rv3766_C (PF27131.1).

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

Curated reference (UniProt)

UniProt I6Y3Z2 TrEMBL · unreviewed · Evidence at protein level
UniProt nameN-acetylmuramoyl-L-alanine amidase domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
V Defense mechanisms
eggNOG descriptionN-acetylmuramoyl-L-alanine amidase
Orthologous groupCOG3023

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 1.802 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 11 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
Amidase_2PF01510.31 2.0e-1737–173 N-acetylmuramoyl-L-alanine amidase
Rv3766_CPF27131.1 2.2e-10218–256 Rv3766 C-terminal domain

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

Closest characterised functional partner: Rv1230c (membrane protein), medium confidence from genomic context alone (score 685 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1230c membrane protein 704 685 ctx cooccurence:683
Rv1443c hyp hypothetical protein 675 675 ctx cooccurence:675
Rv3879c espK ESX-1 secretion-associated protein EspK 673 672 ctx cooccurence:669
Rv3877 eccD1 ESX-1 secretion system protein EccD1 629 630 ctx cooccurence:628
Rv1288 hyp hypothetical protein 669 627 ctx cooccurence:622
Rv1921c lppF lipoprotein LppF 623 624 ctx cooccurence:617
Rv3882c eccE1 ESX-1 secretion system protein EccE1 623 623 ctx cooccurence:622
Rv2164c hyp hypothetical protein 621 621 ctx cooccurence:616
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 597 595 ctx cooccurence:592
Rv0341 iniB isoniazid inducible protein IniB 565 566 ctx cooccurence:560
Rv3593 lpqF lipoprotein LpqF 578 563 ctx neighborhood:495
Rv0613c hyp hypothetical protein 554 554 ctx cooccurence:553
Rv3365c hyp hypothetical protein 537 535 ctx cooccurence:529
Rv2735c hyp hypothetical protein 526 526 ctx cooccurence:525
Rv3472 hyp hypothetical protein 524 525 ctx cooccurence:511

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: N-acetylmuramoyl-L-alanine amidase
  • Pfam (hmmscan --cut_ga): Amidase_2 PF01510.31 (E=2e-17), Rv3766_C PF27131.1 (E=2e-10)
  • (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_218111.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Amidase_2 (PF01510.31), Rv3766_C (PF27131.1)
  • 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 COG3023
  • Curated reference: UniProt I6Y3Z2 (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 — 63 functional partner(s); context anchor Rv1230c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003813|Rv3594|
MGWIGDPIWLEEVLRPALGERLRVLDGWRERGHGDFRDIRGVMWHHTGNSRETAKSIARGRPDLPGPLANLHIAHSGVVTIVAVGVCWHAGRGSYPWLPTDNANWHMIGVECAWPTIRRDGSYDAGERWPDAQIVSMRDVAAALTLKLGYGPERNIGHKEYAGAAQGKWDPGNLSMDWFRAEVAKDTRGEFDHPLTPPPAVIARPPILPKPRNPRDDRILLEEVWDQLRGIEGRGWPVLGDKTIVDYLAELGNKVDALAAKLDAREGLDRPSDTR