Rv3899c Family assigned · medium
H37Rv Rv3899c · MTBC0 - ·
410 aa · 4384147–4385379 (-) ·
RefSeq NP_218416.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Secreted protein (found in culture filtrate), conserved across mycobacteria, with an X-ray crystal structure of fragment 184-410 that defines a new protein family (an alpha/beta/alpha sandwich + alpha-helix bundle; no structures for homologues previously known). Immunoglobulin-like, candidate vaccine antigen. Molecular function unknown. (UniProt auto-name 'Tat' is a database artefact and is not adopted.) |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O05446
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Tat |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2A1TI |
|---|
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) pseudogene candidate
| pN/pS | 0.315 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 35 synonymous, 27 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 25.75% of strains (37389) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF5632 | PF18646.7 | 3.1e-32 | 195–276 | Family of unknown function (DUF5632) |
DUF5631 | PF18645.7 | 3.7e-34 | 304–397 | Family of unknown function (DUF5631) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccD2 (ESX-2 secretion system protein EccD), high confidence from genomic context alone (score 880 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) |
|---|---|---|---|---|
Rv3887c eccD2 |
ESX-2 secretion system protein EccD | 879 | 880 ctx | cooccurence:772 coexpression:430 |
Rv3895c eccB2 |
ESX-2 secretion system protein EccB | 830 | 824 ctx | cooccurence:739 |
Rv3894c eccC2 |
ESX-2 type VII secretion system protein EccC | 784 | 785 ctx | cooccurence:689 |
Rv3900c hyp |
hypothetical protein | 969 | 775 ctx | neighborhood:774 textmining:870 |
Rv2423 hyp |
hypothetical protein | 772 | 772 ctx | cooccurence:771 |
Rv0977 PE_PGRS16 |
PE-PGRS family protein PE_PGRS16 | 778 | 770 ctx | cooccurence:688 |
Rv3166c hyp |
hypothetical protein | 758 | 758 ctx | cooccurence:758 |
Rv0256c PPE2 |
PPE family protein PPE2 | 748 | 749 ctx | cooccurence:747 |
Rv2067c hyp |
hypothetical protein | 748 | 748 ctx | cooccurence:748 |
Rv1435c hyp |
hypothetical protein | 745 | 746 ctx | cooccurence:744 |
Rv2079 hyp |
hypothetical protein | 738 | 739 ctx | cooccurence:728 |
Rv3446c hyp |
hypothetical protein | 738 | 739 ctx | cooccurence:735 |
Rv1006 hyp |
hypothetical protein | 738 | 739 ctx | cooccurence:737 |
Rv3435c |
transmembrane protein | 727 | 728 ctx | cooccurence:725 |
Rv3448 eccD4 |
ESX-4 secretion system protein EccD4 | 724 | 725 ctx | cooccurence:533 coexpression:432 |
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
- Crystal structure of fragment 184-410; first structure of a new protein family (Liu 2016, PMID 27487929)
- Secreted (culture filtrate); immunoglobulin-like fold; interacts with ESX-2 / PE-PPE (Das 2021, PMID 34228167)
- 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_218416.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF5632 (PF18646.7), DUF5631 (PF18645.7)
- 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
2A1TI - Curated reference: UniProt O05446 (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 —
120 functional partner(s); context anchor
eccD2 - Primary literature: Liu Y, Gao Y, Li D, Fleming J, Li H, Bi L (2016). Crystal structure of Rv3899c(184-410), a hypothetical protein from Mycobacterium tuberculosis Acta Crystallogr F 72(Pt 8):642-5. doi:10.1107/S2053230X16010943 PMID:27487929
- Primary literature: Das R, Eniyan K, Bajpai U (2021). Computational identification and characterization of antigenic properties of Rv3899c of Mycobacterium tuberculosis and its interaction with human leukocyte antigen (HLA) Immunogenetics 73(5):357-368. doi:10.1007/s00251-021-01220-x PMID:34228167
Ancestral MTBC0 protein sequence
>H37Rv|Rv3899c| MVTGQPAAAGAHSLSEGAMTAMQSGSVPPPQATPPITTPPVVSAPTMAAGIEATHGPVDTPANTSGAPPASTGTTGPVAPTVVTAGPVAAPAAPVVGGSAVPAGPLPAYGSDLRPPVVAAPAVPSVPTAPVSGAPVAPSASSAPSAGGALVSPVERAASKAVAGQAGASSSTMAGASALSATAGATAGAVSARAAEQQRLQRIVDAVARQEPRISWAAGLRDDGTTTLLVTDLAGGWIPPHVRLPANVTLLEPTARRRDADVIDLLGAVVAVAAHESNTYVAEPGPDAPALTGDRSARSAIPKVDEFGPTLVEAVRRRDSLPRIAQAIALPAVRKTGVLENEAELLHGCITAVKESVLKAYPSHELTAVGDWMLLAAIEALIDEQDYLANYHLAWYAVTTRRGGSRGFAA