Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane protein |
|---|
| MTBC0 PGAP re-annotation | DUF2304 domain-containing protein |
|---|
| Revised (this work) | Small membrane protein that potentiates galactosamine modification of arabinogalactan. RefSeq leaves it of unknown function. Rv3632 is co-transcribed with ppgS (Rv3631, polyprenyl-phospho-N-acetyl-galactosaminyl synthase) and increases PpgS catalytic activity 40-50-fold, supporting the GalN modification of arabinogalactan (Skovierova 2010). Its cell-envelope peptides also bind host cells (adhesion). |
|---|
Curated reference (UniProt)
| UniProt |
I6YGT7
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | Possible conserved membrane protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | Uncharacterized conserved protein (DUF2304) |
|---|
| Orthologous group | COG2456 |
|---|
| KEGG orthology |
K09153
|
|---|
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 |
0.688 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 2 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 |
|---|
DUF2304 | PF10066.15 |
9.1e-31 | 3–107 |
Uncharacterized conserved protein (DUF2304) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv3631 (transferase),
high confidence from genomic context alone
(score 971 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3631 |
transferase |
996 |
971 ctx |
neighborhood:881 cooccurence:760 textmining:870 |
Rv3630 |
integral membrane protein |
987 |
937 ctx |
neighborhood:818 cooccurence:664 textmining:806 |
Rv3779 |
transmembrane protein |
893 |
787 ctx |
cooccurence:768 textmining:519 |
Rv1510 hyp |
hypothetical protein |
726 |
723 ctx |
cooccurence:656 |
Rv3629c |
integral membrane protein |
952 |
651 ctx |
neighborhood:646 textmining:870 |
Rv3633 hyp |
hypothetical protein |
931 |
496 ctx |
neighborhood:493 textmining:870 |
Rv0517 |
acyltransferase |
474 |
475 ctx |
cooccurence:454 |
Rv0048c |
membrane protein |
474 |
475 ctx |
cooccurence:470 |
Rv3634c galE1 |
UDP-glucose 4-epimerase |
868 |
358 |
textmining:804 |
Rv3784 |
dTDP-glucose 4,6-dehydratase |
496 |
148 |
textmining:433 |
Rv3789 |
GtrA family protein |
624 |
99 |
textmining:600 |
Rv3468c |
dTDP-glucose 4,6-dehydratase |
662 |
71 |
textmining:652 |
Rv0230c php |
phosphotriesterase |
520 |
47 |
textmining:517 |
Rv1077 cbs |
cystathionine beta-synthase |
434 |
47 |
textmining:431 |
Rv0007 |
membrane protein |
626 |
42 |
textmining:626 |
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
- Co-transcribed with ppgS; boosts PpgS activity 40-50x for arabinogalactan GalN modification (Skovierova 2010, PMID 21030587)
- Cell-envelope protein; host-cell binding peptides (Sanchez-Barinas 2019, PMID 31111070)
- 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_218149.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2304 (PF10066.15)
- 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
COG2456
- Curated reference: UniProt
I6YGT7
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
15 functional partner(s); context anchor
Rv3631
- Primary literature: Skovierova H, Larrouy-Maumus G, Pham H, Belanova M, Barilone N, Dasgupta A, Mikusova K, Gicquel B, Gilleron M, Brennan PJ, Puzo G, Nigou J, Jackson M (2010). Biosynthetic origin of the galactosamine substituent of Arabinogalactan in Mycobacterium tuberculosis J Biol Chem 285(53):41348-55.
doi:10.1074/jbc.M110.188110 PMID:21030587
Ancestral MTBC0 protein sequence
>mtbc0_003849|Rv3632|
MNWIQVLLIASIIGLLFYLLRSRRSARSRAWVKVGYVLFVLAGIYAVLRPDDTTVVANWFGVRRGTDLMLYALVMAFSFTTLSTYMRFKDLELRYARIARALALEGAQAPEQCR
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