Rv2560 Family assigned · low
H37Rv Rv2560 · MTBC0 mtbc0_002728 ·
325 aa · 2903620–2904597 (+) ·
RefSeq NP_217076.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF2189 domain-containing protein |
| Revised (this work) | Membrane protein (33 kDa) localised to the mycobacterial membrane (immuno-EM); its high-activity binding peptides bind alveolar epithelial (A549) and monocyte (U937) cells and inhibit host-cell invasion, implicating it in adhesion/invasion of monocytes and epithelial cells. Molecular function unfixed. |
Curated reference (UniProt)
| UniProt |
P9WLA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2560 |
UniProt still lists this protein as Uncharacterized protein Rv2560; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| eggNOG description | Zn-ribbon protein possibly nucleic acid-binding |
| Orthologous group | COG5473 |
| 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 | 1.699 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 9 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).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 89.0 (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 |
|---|---|---|---|---|
7w5z-assembly1_c3 |
0.33 | 0.45 | 2.7e+00 | 7w5z-assembly1_c3 Cryo-EM structure of Tetrahymena thermophila mitochondrial complex IV, composite dimer model |
5gpy-assembly1_A |
0.28 | 0.55 | 6.8e+00 | 5gpy-assembly1_A Crystal structure of the human TFIIE complex |
8bqs-assembly1_Dc |
0.16 | 0.43 | 5.4e+00 | 8bqs-assembly1_Dc Cryo-EM structure of the I-II-III2-IV2 respiratory supercomplex from Tetrahymena thermophila |
8oyy-assembly2_B |
0.12 | 0.24 | 1.2e+00 | 8oyy-assembly2_B De novo designed soluble GPCR-like fold GLF_32 |
2nrq-assembly1_A |
0.11 | 0.38 | 7.9e+00 | 2nrq-assembly1_A Crystal structure of protein SSO0741 from Sulfolobus solfataricus, Pfam DUF54 |
8oyx-assembly2_B |
0.08 | 0.29 | 4.6e+00 | 8oyx-assembly2_B De novo designed soluble GPCR-like fold GLF_18 |
6tjv-assembly1_F |
0.07 | 0.23 | 3.2e+00 | 6tjv-assembly1_F Structure of the NDH-1MS complex from Thermosynechococcus elongatus |
5oxf-assembly1_C |
0.06 | 0.24 | 3.8e+00 | 5oxf-assembly1_C An oligomerised bacterial dynamin pair provides a mechanism for the long range sensing and tethering of membranes |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: papA2 (trehalose-2-sulfate acyltransferase), medium confidence from genomic context alone (score 667 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) |
|---|---|---|---|---|
Rv2559c hyp |
hypothetical protein | 773 | 774 ctx | neighborhood:773 |
Rv3820c papA2 |
trehalose-2-sulfate acyltransferase | 666 | 667 ctx | cooccurence:659 |
Rv1182 papA3 |
acyltransferase papA3 | 634 | 635 ctx | cooccurence:634 |
Rv3824c papA1 |
acyltransferase | 630 | 630 ctx | cooccurence:630 |
Rv2566 hyp |
hypothetical protein | 610 | 610 ctx | neighborhood:609 |
Rv2567 hyp |
hypothetical protein | 609 | 609 ctx | neighborhood:609 |
Rv2923c hyp |
hypothetical protein | 573 | 573 ctx | cooccurence:573 |
Rv0538 |
membrane protein | 568 | 569 ctx | cooccurence:566 |
Rv0523c hyp |
hypothetical protein | 562 | 562 ctx | cooccurence:557 |
Rv2937 drrB |
daunorubicin ABC transporter permease DrrB | 512 | 512 ctx | cooccurence:512 |
Rv3903c cpnT hyp |
hypothetical protein | 505 | 505 ctx | cooccurence:505 |
Rv3181c vapB49 |
antitoxin VapB45 | 499 | 499 ctx | cooccurence:499 |
Rv3033 hyp |
hypothetical protein | 497 | 498 ctx | cooccurence:496 |
Rv3732 hyp |
hypothetical protein | 488 | 489 ctx | cooccurence:487 |
Rv0801 hyp |
hypothetical protein | 488 | 489 ctx | cooccurence:485 |
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 protein; binding peptides bind A549/U937 and inhibit invasion (Plaza 2007, PMID 18005255)
- 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_217076.1)
- 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
COG5473 - Curated reference: UniProt P9WLA1 (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 89.0, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
30 functional partner(s); context anchor
papA2 - Primary literature: Plaza DF, Curtidor H, Patarroyo MA, Chapeton-Montes JA, Reyes C, Barreto J, Patarroyo ME (2007). The Mycobacterium tuberculosis membrane protein Rv2560 - biochemical and functional studies FEBS J 274(24):6352-64. doi:10.1111/j.1742-4658.2007.06153.x PMID:18005255
Ancestral MTBC0 protein sequence
>mtbc0_002728|Rv2560| MSQPPEHPGNPADPQGGNQGAGSYPPPGYGAPPPPPGYGPPPGTYLPPGYNAPPPPPGYGPPPGPPPPGYPTHLQSSGFSVGDAISWSWNRFTQNAVTLVVPVLAYAVALAAVIGATAGLVVALSDRATTAYTNTSGVSSESVDITMTPAAGIVMFLGYIALFALVLYMHAGILTGCLDIADGKPVTIATFFRPRNLGLVLVTGLLIVALTFIGGLLCVIPGLIFGFVAQFAVAFAVDRSTSPIDSVKASIETVGSNIGGSVLSWLAQLTAVLVGELLCFVGMLIGIPVAALIHVYTYRKLSGGQVVEAVRPAPPVGWPPGPQLA