hspX Resolved · high auto-curated

H37Rv Rv2031c · MTBC0 mtbc0_002164 · 144 aa · 2307111–2307545 (-) · RefSeq NP_216547.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alpha-crystallin
MTBC0 PGAP re-annotationalpha-crystallin HspX
Revised (this work)Alpha-crystallin HspX. Pfam: HSP20 (PF00011.28), ArsA_HSP20 (PF17886.8).

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

Curated reference (UniProt)

UniProt P9WMK1 SwissProt · reviewed · Evidence at protein level
UniProt nameAlpha-crystallin
Curated functionActs as a chaperone, as it has a significant ability to suppress the thermal denaturation of alcohol dehydrogenase. Cells overexpressing this gene grow more slowly than wild-type cells, and are less susceptible to autolysis following saturation of the culture in vitro, suggesting this protein may slow down the growth rate of M.tuberculosis in culture and by extension during macrophage infection.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namehspX
eggNOG descriptionBelongs to the small heat shock protein (HSP20) family
Orthologous groupCOG0071
KEGG orthology K13993
KEGG pathways map04141
Gene Ontology (89) GO:0001666, GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006457 +77 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 0.321 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 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
HSP20PF00011.28 1.4e-2445–140 Hsp20/alpha crystallin family
ArsA_HSP20PF17886.8 1.8e-0648–125 HSP20-like domain found in ArsA

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

Closest characterised functional partner: acg (NAD(P)H nitroreductase), high confidence from genomic context alone (score 932 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2030c hyp hypothetical protein 980 966 ctx neighborhood:792 coexpression:804 textmining:452
Rv2032 acg NAD(P)H nitroreductase 967 932 ctx neighborhood:531 coexpression:860 textmining:548
Rv1738 hyp hypothetical protein 963 906 coexpression:860 textmining:630
Rv1996 universal stress protein 916 893 coexpression:864
Rv3134c universal stress protein 941 871 coexpression:843 textmining:564
Rv3131 NAD(P)H nitroreductase 918 864 coexpression:860 textmining:429
Rv0079 hyp hypothetical protein 910 864 coexpression:862
Rv2626c hrp1 hypoxic response protein 950 863 coexpression:859 textmining:654
Rv3130c tgs1 diacyglycerol O-acyltransferase 942 862 coexpression:861 textmining:602
Rv3127 hyp hypothetical protein 909 861 coexpression:860
Rv2007c fdxA ferredoxin 947 860 coexpression:860 textmining:640
Rv2623 TB31.7 universal stress protein 971 856 coexpression:827 textmining:812
Rv1733c transmembrane protein 936 837 coexpression:804 textmining:625
Rv0080 hyp hypothetical protein 872 833 coexpression:829
Rv2627c hyp hypothetical protein 810 810 coexpression:805

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: alpha-crystallin
  • MTBC0 PGAP product: alpha-crystallin HspX
  • Pfam (hmmscan --cut_ga): HSP20 PF00011.28 (E=1e-24), ArsA_HSP20 PF17886.8 (E=2e-06)
  • (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_216547.1)
  • Domains: Pfam-A via hmmscan --cut_ga — HSP20 (PF00011.28), ArsA_HSP20 (PF17886.8)
  • 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 COG0071
  • Curated reference: UniProt P9WMK1 (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 — 89 functional partner(s); context anchor acg
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002164|Rv2031c|hspX
MATTLPVQRHPRSLFPEFSELFAAFPSFAGLRPTFDTRLMRLEDEMKEGRYEVRAELPGVDPDKDVDIMVRDGQLTIKAERTEQKDFDGRSEFAYGSFVRTVSLPVGADEDDIKATYDKGILTVSVAVSEGKPTEKHIQIRSTN