Rv2599 Family assigned · low
H37Rv Rv2599 · MTBC0 mtbc0_002766 ·
143 aa · 2951030–2951461 (+) ·
RefSeq NP_217115.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4247 domain-containing protein |
| Revised (this work) | Membrane protein identified as a novel adhesin of M. tuberculosis: it binds the host extracellular-matrix proteins fibronectin, laminin and collagen (Kumar 2013). Also explored as a vaccine antigen. Molecular function = ECM-binding adhesin; further detail unfixed. |
Curated reference (UniProt)
| UniProt |
P9WL69
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2599 |
UniProt still lists this protein as Uncharacterized protein Rv2599; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4247) |
| Orthologous group | 2BFFD |
| Gene Ontology (2) |
GO:0005575, GO:0005576
|
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 | 0.72 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (204) · 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 |
|---|---|---|---|---|
DUF4247 | PF14042.12 | 4.7e-43 | 19–135 | Domain of unknown function (DUF4247) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2597 (membrane protein), high confidence from genomic context alone (score 876 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2598 hyp |
hypothetical protein | 888 | 888 ctx | neighborhood:881 |
Rv2597 |
membrane protein | 875 | 876 ctx | neighborhood:874 |
Rv2600 |
integral membrane protein | 793 | 793 ctx | neighborhood:783 |
Rv2601 speE |
spermidine synthase | 650 | 650 ctx | neighborhood:638 |
Rv2596 vapC40 |
ribonuclease VapC40 | 545 | 545 ctx | neighborhood:544 |
Rv2595 vapB40 |
antitoxin VapB40 | 544 | 544 ctx | neighborhood:544 |
Rv3717 hyp |
hypothetical protein | 724 | 47 | textmining:723 |
Rv3500c yrbE4B |
integral membrane protein | 513 | 46 | textmining:511 |
Rv3501c yrbE4A |
integral membrane protein | 426 | 46 | textmining:423 |
Rv0071 |
maturase | 513 | 45 | textmining:511 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 644 | 44 | textmining:643 |
Rv3505 fadE27 |
acyl-CoA dehydrogenase FadE27 | 430 | 42 | textmining:430 |
Rv0309 hyp |
hypothetical protein | 808 | 41 | textmining:808 |
Rv3838c pheA |
prephenate dehydratase | 578 | 41 | textmining:578 |
Rv3062 ligB |
DNA ligase | 436 | 41 | textmining:436 |
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
- Membrane adhesin binding fibronectin/laminin/collagen (Kumar 2013, PMID 23922800)
- 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_217115.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4247 (PF14042.12)
- 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
2BFFD - Curated reference: UniProt P9WL69 (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 —
16 functional partner(s); context anchor
Rv2597 - Primary literature: Kumar S, Puniya BL, Parween S, Nahar P, Ramachandran S (2013). Identification of novel adhesins of M. tuberculosis H37Rv using integrated approach of multiple computational algorithms and experimental analysis PLoS One 8(7):e69790. doi:10.1371/journal.pone.0069790 PMID:23922800
Ancestral MTBC0 protein sequence
>mtbc0_002766|Rv2599| MSRNRLFLVAGILAVAAAVSLISGITLLNRDVGSYIASHYRQESRDVNGTRYLCTGSPKQVATTLVKYQTPAARASHTDTEYLRYRNNIVTVGPDGTYPCIIRVENLSAGYNHGAYVFLGPGFTPGSPSGGSGGSPGGPGGSK