MTBC Gene Atlas

lipZ Family assigned · medium auto-curated

H37Rv Rv1834 · MTBC0 mtbc0_001947 · 288 aa · 2097862–2098728 (+) · RefSeq NP_216350.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationalpha/beta hydrolase
Revised (this work)Alpha/beta hydrolase. Pfam: Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14).

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

Curated reference (UniProt)

UniProt P9WLR1 SwissProt · reviewed · Inferred from homology
UniProt namePutative hydrolase LipZ
EC (curated) EC 3.-.-.-

UniProt still lists this protein as Putative hydrolase LipZ; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionAlpha beta hydrolase
Orthologous groupCOG0596

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 1.45 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 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
Abhydrolase_1PF00561.27 6.0e-2033–275 alpha/beta hydrolase fold
Hydrolase_4PF12146.16 1.5e-0634–244 Serine aminopeptidase, S33
Abhydrolase_6PF12697.14 1.9e-1736–281 Alpha/beta hydrolase family

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

Closest characterised functional partner: PE_PGRS37 (PE-PGRS family protein PE_PGRS37), high confidence from genomic context alone (score 700 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2126c PE_PGRS37 PE-PGRS family protein PE_PGRS37 700 700 ctx cooccurence:700
Rv1833c dhmA2 haloalkane dehalogenase 667 667 ctx neighborhood:575
Rv1243c PE_PGRS23 PE-PGRS family protein PE_PGRS23 659 659 ctx cooccurence:659
Rv2579 dhaA haloalkane dehalogenase 572 573 ctx cooccurence:570
Rv1106c 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase 569 570 ctx cooccurence:554
Rv2627c hyp hypothetical protein 551 535
Rv0130 htdZ 3-hydroxyl-thioester dehydratase 521 521 ctx neighborhood:516
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 529 501 experimental:441
Rv2940c mas multifunctional mycocerosic acid synthase 527 500 experimental:441
Rv1527c pks5 polyketide synthase 526 498 experimental:441
Rv2048c pks12 polyketide synthase 526 498 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 526 498 experimental:441
Rv3829c dehydrogenase 495 496 ctx cooccurence:478
Rv0124 PE_PGRS2 PE-PGRS family protein PE_PGRS2 480 480 ctx cooccurence:480
Rv2853 PE_PGRS48 PE-PGRS family protein PE_PGRS48 479 479 ctx cooccurence:479

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: hydrolase
  • MTBC0 PGAP product: alpha/beta hydrolase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=6e-20), Hydrolase_4 PF12146.16 (E=2e-06), Abhydrolase_6 PF12697.14 (E=2e-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_216350.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Hydrolase_4 (PF12146.16), Abhydrolase_6 (PF12697.14)
  • 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 COG0596
  • Curated reference: UniProt P9WLR1 (SwissProt, reviewed; Inferred from homology)
  • 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 — 42 functional partner(s); context anchor PE_PGRS37
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001947|Rv1834|lipZ
MTSPSVREWRDGGRWLPTAVGKVFVRSGPGDTPTMLLLHGYPSSSFDFRAVIPHLTGQAWVTMDFLGFGLSDKPRPHRYSLLEQAHLVETVVAHTVTGAVVVLAHDMGTSVTTELLARDLDGRLPFDLRRAVLSNGSVILERASLRPIQKVLRSPLGPVAARLVSRGGFTRGFGRIFSPAHPLSAQEAQAQWELLCYNDGNRIPHLLISYLDERIRHAQRWHGAVRDWPKPLGFVWGLDDPVATTNVLNGLRELRPSAAVVELPGLGHYPQVEAPKAYAEAALSLLVD