Rv3376 Family assigned · medium auto-curated

H37Rv Rv3376 · MTBC0 mtbc0_003591 · 217 aa · 3816873–3817526 (+) · RefSeq NP_217893.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphatase
MTBC0 PGAP re-annotationHAD family phosphatase
Revised (this work)HAD family phosphatase. Pfam: Hydrolase (PF00702.33), HAD_2 (PF13419.13), Hydrolase_like (PF13242.13).

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

Curated reference (UniProt)

UniProt P9WMS5 SwissProt · reviewed · Evidence at protein level
UniProt namePhosphatase Rv3376
EC (curated) EC 3.1.-.-
Curated functionAble to hydrolyze geranyl diphosphate (GPP), farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) to respectively yield geraniol, farnesol and geranylgeraniol.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionHaloacid dehalogenase-like hydrolase
Orthologous groupCOG1011
EC number EC 3.1.3.10
KEGG orthology K07025, K20866
KEGG pathways map00010, map01120
Gene Ontology (13) GO:0003674, GO:0003824, GO:0006793, GO:0006796, GO:0008150, GO:0008152, GO:0009987, GO:0016311, GO:0016787, GO:0016788, GO:0016791, GO:0042578 +1 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 0.249 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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
HydrolasePF00702.33 1.7e-233–185 haloacid dehalogenase-like hydrolase
HAD_2PF13419.13 1.1e-1091–190 Haloacid dehalogenase-like hydrolase
Hydrolase_likePF13242.13 1.4e-04147–200 HAD-hyrolase-like

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

Closest characterised functional partner: echA18 (enoyl-CoA hydratase), medium confidence from genomic context alone (score 557 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1043c hyp hypothetical protein 648 645 database:543
Rv3671c marP serine protease 575 572 database:543
Rv1223 htrA serine protease HtrA 575 571 database:543
Rv0983 pepD serine protease PepD 572 569 database:543
Rv0125 pepA serine protease PepA 571 567 database:543
Rv3373 echA18 enoyl-CoA hydratase 777 557 ctx neighborhood:531 textmining:518
Rv3374 echA18.1 Probable enoyl-CoA hydratase EchA18.1 (Enoyl hydrase) (Unsaturated acyl-CoA hydratase) (Crotonase); Rv3374, (MTV004.32), len: 82 aa. Probabl 630 553 ctx neighborhood:531
Rv3375 amiD amidase 823 541 ctx neighborhood:532 textmining:630
Rv3372 otsB2 trehalose 6-phosphate phosphatase 582 453
Rv3554 fdxB electron transfer protein FdxB 438 439
Rv2307c hyp hypothetical protein 453 436 database:422
Rv2627c hyp hypothetical protein 451 435 database:422
Rv2524c fas fatty acid synthase 431 399
Rv0752c fadE9 acyl-CoA dehydrogenase FadE9 419 397
Rv0033 acpA acyl carrier protein AcpA 445 366

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: phosphatase
  • MTBC0 PGAP product: HAD family phosphatase
  • Pfam (hmmscan --cut_ga): Hydrolase PF00702.33 (E=2e-23), HAD_2 PF13419.13 (E=1e-10), Hydrolase_like PF13242.13 (E=1e-04)
  • (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_217893.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Hydrolase (PF00702.33), HAD_2 (PF13419.13), Hydrolase_like (PF13242.13)
  • 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 COG1011
  • Curated reference: UniProt P9WMS5 (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 — 40 functional partner(s); context anchor echA18
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003591|Rv3376|
MSISAVVFDRDGVLTSFDWTRAEEDVRRITGLPLEEIERRWGGWLNGLTIDDAFVETQPISEFLSSLARELELGSKARDELVRLDYMAFAQGYPDARPALEEARRRGLKVGVLTNNSLLVSARSLLQCAALHDLVDVVLSSQMIGAAKPDPRAYQAIAEALGVSTTSCLFFDDIADWVEGARCAGMRAYLVDRSGQTRDGVVRDLSSLGAILDGAGP