Rv1225c Family assigned · medium auto-curated

H37Rv Rv1225c · MTBC0 mtbc0_001313 · 276 aa · 1376335–1377165 (-) · RefSeq NP_215741.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationHAD-IIA family hydrolase
Revised (this work)HAD-IIA family hydrolase. Pfam: Hydrolase_6 (PF13344.13), 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 O33221 TrEMBL · unreviewed · Evidence at protein level
UniProt nameHaloacid dehalogenase-like hydrolase domain-containing protein 2

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionHydrolase
Orthologous groupCOG0647
KEGG orthology K02566

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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 2 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 25.67% of strains (37276) · clonal

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
Hydrolase_6PF13344.13 4.5e-2311–106 Haloacid dehalogenase-like hydrolase
HydrolasePF00702.33 2.6e-09174–232 haloacid dehalogenase-like hydrolase
HAD_2PF13419.13 1.1e-05182–237 Haloacid dehalogenase-like hydrolase
Hydrolase_likePF13242.13 1.4e-20192–269 HAD-hyrolase-like

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

Closest characterised functional partner: Rv1226c (transmembrane protein), medium confidence from genomic context alone (score 642 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1226c transmembrane protein 641 642 ctx neighborhood:577
Rv1227c transmembrane protein 573 574 ctx neighborhood:571
Rv0018c pstP phosphoserine/threonine phosphatase PstP 455 432
Rv1712 cmk cytidylate kinase 419 419
Rv3760 membrane protein 418 419 coexpression:419
Rv2966c rsmD methyltransferase 412 413 coexpression:402
Rv1539 lspA lipoprotein signal peptidase 409 410

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: HAD-IIA family hydrolase
  • Pfam (hmmscan --cut_ga): Hydrolase_6 PF13344.13 (E=4e-23), Hydrolase PF00702.33 (E=3e-09), HAD_2 PF13419.13 (E=1e-05), Hydrolase_like PF13242.13 (E=1e-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_215741.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Hydrolase_6 (PF13344.13), 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 COG0647
  • Curated reference: UniProt O33221 (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 — 7 functional partner(s); context anchor Rv1226c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001313|Rv1225c|
MDVAHLMAAAVLFDIDGVLVLSWRAIPGAAETVRQLTHRGIACAYLTNTTTRTRRQIAEALGAAGIPVAADDVITAGVLTAEYLHGAYPGARCFLVNNGDITEDLPGIDVVLSTEIGPEDCPEAPDVVVLGSAGPQFDHRTLSRVYGWMLDGVPVVAMHRNMTWNTTDGLRIDTGMYLTGMEQACGKTATAIGKPAAEGFLAAADRVGVDPQQMVMIGDDLHNDVLAAQAVGMTGVLVRTGKFRQQTLDRWLAGASATRPHHVIDSVAGLPPLLGC