Rv3166c Family assigned · low
H37Rv Rv3166c · MTBC0 mtbc0_003365 ·
319 aa · 3559240–3560199 (-) ·
RefSeq NP_217682.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4129 domain-containing protein |
| Revised (this work) | Cell-surface protein (immuno-EM); its high-activity binding peptides bind A549 and U937 cells and inhibit mycobacterial invasion (by up to 94%), implicating it in host-cell adhesion/invasion. Pfam DUF4129. Molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
O53316
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Protein-glutamine gamma-glutamyltransferase-like C-terminal domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4129) |
| Orthologous group | 2ESVE |
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 | 0.271 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 5 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 |
|---|---|---|---|---|
DUF4129 | PF13559.12 | 9.1e-14 | 237–307 | Domain of unknown function (DUF4129) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 77.3 (confident). A confident model makes the fold comparison meaningful.
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 |
|---|---|---|---|---|
9ftz-assembly1_S |
0.92 | 0.36 | 3.7e-02 | 9ftz-assembly1_S CIII2/CIV respiratory supercomplex from Mycobacterium smegmatis with lansoprazole sulfide |
9dm1-assembly1_S |
0.66 | 0.29 | 6.8e-02 | 9dm1-assembly1_S Mycobacterial supercomplex malate:quinone oxidoreductase assembly |
6ylh-assembly1_b |
0.02 | 0.23 | 7.0e+00 | 6ylh-assembly1_b Rix1-Rea1 pre-60S particle - full composite structure |
7v08-assembly1_b |
0.02 | 0.23 | 5.9e+00 | 7v08-assembly1_b Nucleoplasmic pre-60S intermediate of the Nog2 containing pre-rotation state from a Spb1 D52A suppressor 3 strain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moxR3 (methanol dehydrogenase transcriptional regulator MoxR), high confidence from genomic context alone (score 882 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) |
|---|---|---|---|---|
Rv3163c hyp |
hypothetical protein | 961 | 962 ctx | neighborhood:841 cooccurence:769 |
Rv3165c hyp |
hypothetical protein | 908 | 908 ctx | neighborhood:882 |
Rv3164c moxR3 |
methanol dehydrogenase transcriptional regulator MoxR | 881 | 882 ctx | neighborhood:881 |
Rv3162c |
integral membrane protein | 842 | 842 ctx | neighborhood:841 |
Rv2423 hyp |
hypothetical protein | 765 | 765 ctx | cooccurence:756 |
Rv3899c hyp |
hypothetical protein | 758 | 758 ctx | cooccurence:758 |
Rv3099c hyp |
hypothetical protein | 745 | 745 ctx | cooccurence:745 |
Rv3435c |
transmembrane protein | 745 | 745 ctx | cooccurence:745 |
Rv3843c |
transmembrane protein | 728 | 728 ctx | cooccurence:728 |
Rv1006 hyp |
hypothetical protein | 714 | 714 ctx | cooccurence:714 |
Rv2079 hyp |
hypothetical protein | 712 | 712 ctx | cooccurence:712 |
Rv0048c |
membrane protein | 702 | 702 ctx | cooccurence:701 |
Rv1435c hyp |
hypothetical protein | 690 | 690 ctx | cooccurence:690 |
Rv0875c hyp |
hypothetical protein | 689 | 690 ctx | cooccurence:688 |
Rv0713 |
transmembrane protein | 677 | 677 ctx | cooccurence:677 |
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
- Surface protein; HABPs inhibit host-cell invasion (Ocampo 2012, PMID 22427370)
- Pfam DUF4129
- 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_217682.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4129 (PF13559.12)
- 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
2ESVE - Curated reference: UniProt O53316 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 77.3, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
70 functional partner(s); context anchor
moxR3 - Primary literature: Ocampo M, Aristizabal-Ramirez D, Rodriguez DM, Munoz M, Curtidor H, Vanegas M, Patarroyo MA, Patarroyo ME (2012). The role of Mycobacterium tuberculosis Rv3166c protein-derived high-activity binding peptides in inhibiting invasion of human cell lines Protein Eng Des Sel 25(5):235-42. doi:10.1093/protein/gzs011 PMID:22427370
Ancestral MTBC0 protein sequence
>mtbc0_003365|Rv3166c| MPGTKPGSDKPTGRVVVVIVLLMLAGAALRGHLPADDGAPLAAAGGSRAALMFIVAALAATLALIALAIITRLRHPLPVAPSAGELSAMLGGAAGRPNWRVLLLGLGTILAWLLIAILLARLFVPDDVGPAAPIPDSTATPDASSTTPSRPQPPQDNNDDVLGILFASTIGLFLMVVAGSLITSRRQRKSAPARISGDRIESPAPSARSESLARAAEIGLAEMADLRREPREAIIACYVAMERELSHVPGVAPQDFDTPTEVLARAVEHRALHGASAAALVSLFAEARFSPHVMNEEHREVAMRLLRLVLDELSTRTAI