hbhA Resolved · medium auto-curated

H37Rv Rv0475 · MTBC0 mtbc0_000500 · 199 aa · 569162–569761 (+) · RefSeq NP_214989.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)heparin binding hemagglutinin HbhA
MTBC0 PGAP re-annotationheparin-binding hemagglutinin HbhA
Revised (this work)Heparin-binding hemagglutinin HbhA.

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

Curated reference (UniProt)

UniProt P9WIP9 SwissProt · reviewed · Evidence at protein level
UniProt nameHeparin-binding hemagglutinin
Curated functionRequired for extrapulmonary dissemination. Mediates adherence to epithelial cells by binding to sulfated glycoconjugates present at the surface of these cells; binds heparin, dextran sulfate, fucoidan and chondroitin sulfate. Promotes hemagglutination of erythrocytes of certain host species. Induces mycobacterial aggregation.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namehbhA
eggNOG descriptionRequired for extrapulmonary dissemination. mediates adherence to epithelial cells by binding to sulfated glycoconjugates present at the surface of these cells
Orthologous group2EBKM
KEGG orthology K16645
Gene Ontology (55) GO:0003674, GO:0005488, GO:0005515, GO:0005539, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0007155 +43 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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: Rv0476 (transmembrane protein), high confidence from genomic context alone (score 827 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0477 hyp hypothetical protein 835 829 ctx neighborhood:766
Rv0476 transmembrane protein 827 827 ctx neighborhood:766
Rv0383c ttfA hyp hypothetical protein 772 772 ctx cooccurence:772
Rv3850 hyp hypothetical protein 770 770 ctx cooccurence:768
Rv0996 transmembrane protein 770 770 ctx cooccurence:767
Rv1109c hyp hypothetical protein 768 769 ctx cooccurence:768
Rv0556 transmembrane protein 768 768 ctx cooccurence:768
Rv0817c lmeA hyp hypothetical protein 764 764 ctx cooccurence:764
Rv2732c transmembrane protein 764 764 ctx cooccurence:762
Rv3205c hyp hypothetical protein 760 760 ctx cooccurence:758
Rv1222 rseA anti-sigma E factor RseA 753 754 ctx cooccurence:750
Rv2446c integral membrane protein 751 752 ctx cooccurence:751
Rv3212 hyp hypothetical protein 750 751 ctx cooccurence:747
Rv0358 hyp hypothetical protein 750 751 ctx cooccurence:750
Rv2360c hyp hypothetical protein 750 750 ctx cooccurence:750

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: heparin binding hemagglutinin HbhA
  • MTBC0 PGAP product: heparin-binding hemagglutinin HbhA
  • (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_214989.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 2EBKM
  • Curated reference: UniProt P9WIP9 (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 — 165 functional partner(s); context anchor Rv0476
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000500|Rv0475|hbhA
MAENSNIDDIKAPLLAALGAADLALATVNELITNLRERAEETRTDTRSRVEESRARLTKLQEDLPEQLTELREKFTAEELRKAAEGYLEAATSRYNELVERGEAALERLRSQQSFEEVSARAEGYVDQAVELTQEALGTVASQTRAVGERAAKLVGIELPKKAAPAKKAAPAKKAAPAKKAAAKKAPAKKAAAKKVTQK