hsr1 Resolved · high
H37Rv Rv1435c · MTBC0 mtbc0_001535 ·
209 aa · 1621686–1622315 (-) ·
RefSeq NP_215951.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Hsr1 (host splicing regulator 1), a secreted virulence factor that disrupts host snRNP biogenesis. RefSeq leaves it 'hypothetical'. Secreted Rv1435c/hsr1 targets specific exon-skipping events and facilitates a direct interaction between Mtb phagosomes and U5 snRNA and SNRPF; genetic deletion reverses the splicing changes and attenuates growth ex vivo and in vivo (Chauhan 2025). |
Curated reference (UniProt)
| UniProt |
O06823
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved proline, glycine, valine-rich secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 29WFS |
|---|
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 | 0.623 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1005c pabB |
para-aminobenzoate synthase component I | 820 | 809 | coexpression:648 experimental:461 |
Rv1609 trpE |
anthranilate synthase component I | 819 | 808 | coexpression:647 experimental:461 |
Rv2386c mbtI |
salicylate synthase | 819 | 807 | coexpression:646 experimental:461 |
Rv1006 hyp |
hypothetical protein | 775 | 775 ctx | cooccurence:774 |
Rv1868 hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:773 |
Rv2894c xerC |
tyrosine recombinase XerC | 780 | 770 | coexpression:770 |
Rv2047c hyp |
hypothetical protein | 784 | 761 ctx | cooccurence:756 |
Rv2192c trpD |
anthranilate phosphoribosyltransferase | 781 | 751 | coexpression:737 |
Rv1612 trpB |
tryptophan synthase subunit beta | 776 | 746 | coexpression:731 |
Rv3899c hyp |
hypothetical protein | 745 | 746 ctx | cooccurence:744 |
Rv1613 trpA |
tryptophan synthase subunit alpha | 775 | 745 | coexpression:730 |
Rv3033 hyp |
hypothetical protein | 745 | 745 ctx | cooccurence:745 |
Rv0013 trpG |
anthranilate synthase component II | 774 | 744 | coexpression:729 |
Rv0063 |
oxidoreductase | 740 | 740 | coexpression:740 |
Rv2082 hyp |
hypothetical protein | 738 | 739 ctx | cooccurence:738 |
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
- Secreted protein interacting with host splicing factors; targets exon-skipping (Chauhan 2025, PMID 40601628)
- Links Mtb phagosomes to U5 snRNA / SNRPF; Δhsr1 attenuated in macrophages and mice
- Named hsr1
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_215951.1)
- 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
29WFS - Curated reference: UniProt O06823 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 69.7, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 119 functional partner(s)
- Primary literature: Chauhan K, Datta D, Kapoor Y, Passricha N, Dutt R, Arora N, Das M, Rao K, Singh L, Gautam A, et al. (2025). A Mycobacterium tuberculosis secreted virulence factor Rv1435c/hsr1 disrupts host snRNP biogenesis Proc Natl Acad Sci USA 122(27):e2423349122. doi:10.1073/pnas.2423349122 PMID:40601628
Ancestral MTBC0 protein sequence
>mtbc0_001535|Rv1435c|hsr1 MTLMAIVNRFNIKVIAGAGLFAAAIALSPDAAADPLMTGGYACIQGMAGDAPVAAGDPVAAGGPAAAGACSAALTDMAGVPFVAPGPVPAAAPVPIGAPVPIPGAPVPIPGAPVPIPGAPVPIPGGPVPIPGAPVPVPAVPAPVIPVGTPLIALGPVLAGAPGDGVVSAPIIGMSGVKDALTDPAPAGGPVPGQPVLPGPSASAPAGAR