Rv0556 Family assigned · low
H37Rv Rv0556 · MTBC0 mtbc0_000585 ·
171 aa · 651510–652025 (+) ·
RefSeq NP_215070.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3592 domain-containing protein |
| Revised (this work) | Polymorphic-toxin / contact-dependent immunity-protein-like fold (Tsi4-like). RefSeq leaves it 'membrane protein'. |
Curated reference (UniProt)
| UniProt |
O06422
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved transmembrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2EDS1 |
|---|
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 | 0.568 · 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)
Closest characterised functional partner: menD (bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0555 menD |
bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase | 884 | 884 ctx | neighborhood:882 |
Rv0554 bpoC |
non-heme bromoperoxidase BpoC | 821 | 821 ctx | neighborhood:820 |
Rv0557 mgtA |
GDP-mannose-dependent alpha-mannosyltransferase | 799 | 800 ctx | neighborhood:800 |
Rv2446c |
integral membrane protein | 778 | 778 ctx | cooccurence:774 |
Rv3212 hyp |
hypothetical protein | 777 | 777 ctx | cooccurence:774 |
Rv1632c hyp |
hypothetical protein | 776 | 776 ctx | cooccurence:773 |
Rv3438 hyp |
hypothetical protein | 774 | 775 ctx | cooccurence:774 |
Rv3850 hyp |
hypothetical protein | 774 | 775 ctx | cooccurence:774 |
Rv2732c |
transmembrane protein | 774 | 774 ctx | cooccurence:773 |
Rv1109c hyp |
hypothetical protein | 774 | 774 ctx | cooccurence:773 |
Rv3205c hyp |
hypothetical protein | 773 | 774 ctx | cooccurence:773 |
Rv0996 |
transmembrane protein | 772 | 773 ctx | cooccurence:772 |
Rv0358 hyp |
hypothetical protein | 772 | 772 ctx | cooccurence:772 |
Rv2049c hyp |
hypothetical protein | 771 | 772 ctx | cooccurence:771 |
Rv2138 lppL |
lipoprotein LppL | 771 | 771 ctx | cooccurence:770 |
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
- Foldseek vs AFDB-SwissProt: immune protein Tsi4, TM 0.54, E 2e-6
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
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_215070.1)
- 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
2EDS1 - Curated reference: UniProt O06422 (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 —
150 functional partner(s); context anchor
menD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000585|Rv0556| MISPKPLLHILIHGRSDELPDTRGRIVLRWLRIAVLIVTGLVTLQSVLLVAGAWRNDIAIQRNMGVAQAEVLSAGPRRSTIEFVTPDRITYRPQLGVLYPSELSTGMRIYVEYNKRDPNLVRVQHRNAGLAIIPAGSIAVVAWLIAAAALVVLAVLDKRLERRENSASATG