Rv2468c Resolved · medium
H37Rv Rv2468c · MTBC0 - ·
167 aa · 2771644–2772147 (-) ·
RefSeq NP_216984.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Immunomodulatory / T-cell costimulatory protein: binds integrin VLA-5 (alpha5beta1) via an RGD motif and costimulates T cells. NOTE: a Foldseek hit to the cytochrome bcc:aa3 fold is a FALSE POSITIVE (the Mtb cytochrome bcc is qcrCAB, not this gene). |
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 |
P9WLA7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2468c |
UniProt still lists this protein as Uncharacterized protein Rv2468c; 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 (DUF5130) |
| Orthologous group | COG1512 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF5130 | PF17174.11 | 1.8e-65 | 26–161 | Domain of unknown function (DUF5130) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 68.7 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
8hcr-assembly1_V |
1.00 | 0.80 | 2.4e-18 sig | 8hcr-assembly1_V Cryo-EM structure of the Mycobacterium tuberculosis cytochrome bcc:aa3 supercomplex and a novel inhibitor targeting subunit cytochrome cI |
9dm1-assembly1_V |
1.00 | 0.80 | 3.9e-16 sig | 9dm1-assembly1_V Mycobacterial supercomplex malate:quinone oxidoreductase assembly |
6hwh-assembly2_O |
1.00 | 0.80 | 1.8e-14 sig | 6hwh-assembly2_O Structure of a functional obligate respiratory supercomplex from Mycobacterium smegmatis |
5anp-assembly2_B |
1.00 | 0.81 | 4.8e-04 sig | 5anp-assembly2_B CRYSTAL STRUCTURE OF THE BA41 PROTEIN FROM BIZIONIA ARGENTINENSIS |
3pw9-assembly1_A |
1.00 | 0.79 | 9.0e-04 sig | 3pw9-assembly1_A Structural and functional Analysis of Arabidopsis thaliana thylakoid lumen protein AtTLP18.3 |
5anp-assembly1_A |
1.00 | 0.72 | 5.7e-04 sig | 5anp-assembly1_A CRYSTAL STRUCTURE OF THE BA41 PROTEIN FROM BIZIONIA ARGENTINENSIS |
3ptj-assembly1_A |
1.00 | 0.79 | 1.7e-03 sig | 3ptj-assembly1_A Structural and functional Analysis of Arabidopsis thaliana thylakoid lumen protein AtTLP18.3 |
2kpt-assembly1_A |
1.00 | 0.78 | 2.9e-03 sig | 2kpt-assembly1_A Solution NMR structure of the N-terminal domain of cg2496 protein from Corynebacterium glutamicum. Northeast Structural Genomics Consortium Target CgR26A |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: qcrA (ubiquinol-cytochrome C reductase rieske iron-sulfur subunit), high confidence from genomic context alone (score 893 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) |
|---|---|---|---|---|
Rv2468A hyp |
hypothetical protein | 936 | 937 ctx | neighborhood:882 experimental:484 |
Rv2195 qcrA |
ubiquinol-cytochrome C reductase rieske iron-sulfur subunit | 893 | 893 ctx | cooccurence:544 experimental:747 |
Rv2199c ctaF |
cytochrome c oxidase polypeptide 4 | 829 | 829 | experimental:747 |
Rv2200c ctaC |
cytochrome C oxidase subunit II | 819 | 819 | experimental:783 |
Rv2196 qcrB |
ubiquinol-cytochrome C reductase cytochrome subunit B | 816 | 816 | experimental:783 |
Rv1638A hyp |
hypothetical protein | 816 | 812 ctx | cooccurence:745 |
Rv2469c hyp |
hypothetical protein | 811 | 812 ctx | neighborhood:811 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 810 | 807 ctx | cooccurence:738 |
Rv3043c ctaD |
cytochrome C oxidase cytochrome 1 | 793 | 794 | experimental:783 |
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 791 | 792 | experimental:747 |
Rv2179c |
3'-5' exoribonuclease | 764 | 764 ctx | cooccurence:764 |
Rv2193 ctaE |
cytochrome C oxidase subunit III | 750 | 750 | experimental:747 |
Rv2520c |
membrane protein | 749 | 750 ctx | cooccurence:745 |
Rv1222 rseA |
anti-sigma E factor RseA | 749 | 749 ctx | cooccurence:740 |
Rv1109c hyp |
hypothetical protein | 747 | 747 ctx | cooccurence:741 |
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
- Experimentally characterised as a T-cell costimulatory protein (RGD/VLA-5) by Li et al. 2012
- Structural cytochrome bcc:aa3 hit refuted: that complex is encoded by qcrCAB
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_216984.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF5130 (PF17174.11)
- 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
COG1512 - Curated reference: UniProt P9WLA7 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 68.7, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
95 functional partner(s); context anchor
qcrA - Primary literature: Li J, Ding BY, Thomas WD, et al. (2012). A T-cell costimulatory molecule of Mycobacterium tuberculosis J Leukoc Biol. doi:10.1189/jlb.0711364 PMID:22158781
Ancestral MTBC0 protein sequence
>H37Rv|Rv2468c| MTHRSSRLEVGPVARGDVATIEHAELPPGWVLTTSGRISGVTEPGELSVHYPFPIADLVALDDALTYSSRACQVRFAIYLGDLGRDTAARAREILGKVPTPDNAVLLAVSPNQCAIEVVYGSQVRGRGAESAAPLGVAAASSAFEQGELVDGLISAIRVLSAGIAPG