Rv3446c Family assigned · low auto-curated
H37Rv Rv3446c · MTBC0 mtbc0_003665 ·
404 aa · 3889202–3890416 (-) ·
RefSeq NP_217963.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | type VII secretion-associated protein |
| Revised (this work) | Type VII secretion-associated protein. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06263
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Hypothetical alanine and valine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| eggNOG description | Type VII secretion-associated protein, Rv3446c family, C-terminal domain |
| Orthologous group | COG0443 |
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 | 0.319 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 7 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: eccD4 (ESX-4 secretion system protein EccD4), high confidence from genomic context alone (score 981 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3448 eccD4 |
ESX-4 secretion system protein EccD4 | 989 | 981 ctx | neighborhood:778 cooccurence:428 coexpression:860 textmining:487 |
Rv3447c eccC4 |
ESX-4 secretion system protein EccC4 | 986 | 979 ctx | neighborhood:881 coexpression:831 |
Rv2299c htpG |
chaperone protein HtpG | 977 | 969 | coexpression:668 experimental:772 database:622 |
Rv3449 mycP4 |
membrane-anchored mycosin | 962 | 960 ctx | neighborhood:708 coexpression:852 |
Rv0351 grpE |
stress response protein GrpE | 961 | 947 | coexpression:702 experimental:773 |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 929 | 918 | coexpression:628 experimental:476 database:601 |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 929 | 918 | coexpression:627 experimental:476 database:601 |
Rv3903c cpnT hyp |
hypothetical protein | 867 | 861 | coexpression:770 |
Rv3444c esxT |
ESAT-6 like protein EsxT | 891 | 857 ctx | neighborhood:792 |
Rv3445c esxU |
ESAT-6 like protein EsxU | 861 | 822 ctx | neighborhood:811 |
Rv3196 hyp |
hypothetical protein | 824 | 816 | coexpression:734 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 832 | 808 | coexpression:613 experimental:508 |
Rv2667 clpC2 |
ATP-dependent protease ATP-binding subunit ClpC | 832 | 808 | coexpression:613 experimental:508 |
Rv0384c clpB |
chaperone protein ClpB | 831 | 807 | coexpression:612 experimental:508 |
Rv0440 groEL2 |
molecular chaperone GroEL | 829 | 803 | coexpression:629 experimental: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: type VII secretion-associated protein
- (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_217963.1)
- 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
COG0443 - Curated reference: UniProt O06263 (TrEMBL, unreviewed; Predicted)
- 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 —
335 functional partner(s); context anchor
eccD4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003665|Rv3446c| MSPHRAVIEAGPGAIRRLCCGADVVADTAVSAAALAAIDDQVALLDERPVAVDSLWFDALRSVAVDHRDGPVVVHPSWWSAARVEVVTAAARTLTRDVVVHPRSWLLRQASSGVSAATVVVEIAERLVLVAGAEVAAVARRTDAESVAGQVGSVIARMTRGITAVVLIDVPSTVAGAAALAAAIAGAVRGTGSSVVEIDGVRLARLARAALPPSDEPADPAARPATRSRVPTLARVAAAGVALALLAPAAVVRHGATTLQRPPTTLLVEGRVALTIPADWSTQRVVSGPGSARVQVTSPADPEVALHVTQSPVPGETLPGTAQRLKRAIDASPAGVFVDFNPSDIRAGRPAVTYREVRAGHQVRWTILLDGAVRISVGCQSGPGHEDLLREVCAQAVRSVHAVG