Rv3630 Family assigned · medium
H37Rv Rv3630 · MTBC0 mtbc0_003847 ·
431 aa · 4092879–4094174 (+) ·
RefSeq NP_218147.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Membrane lipid flippase / transporter (Lipid-III-flippase-like fold). RefSeq leaves it 'integral membrane protein'. Resolves the earlier MDR-transporter structural ambiguity toward a lipid-flipping membrane transporter. |
Curated reference (UniProt)
| UniProt |
P9WKX9
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv3630 |
UniProt still lists this protein as Uncharacterized protein Rv3630; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | polysaccharide biosynthetic process |
| Orthologous group | COG2244 |
| 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 | 1.202 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 12 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.54% of strains (781) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3632 (membrane protein), high confidence from genomic context alone (score 937 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3632 |
membrane protein | 987 | 937 ctx | neighborhood:818 cooccurence:664 textmining:806 |
Rv3631 |
transferase | 982 | 909 ctx | neighborhood:818 cooccurence:472 textmining:813 |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 804 | 778 | coexpression:733 |
Rv3809c glf |
UDP-galactopyranose mutase | 772 | 746 | coexpression:731 |
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 773 | 745 | coexpression:730 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 774 | 744 | coexpression:729 |
Rv3779 |
transmembrane protein | 734 | 735 ctx | cooccurence:718 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 713 | 714 ctx | cooccurence:710 |
Rv3629c |
integral membrane protein | 960 | 708 ctx | neighborhood:704 textmining:870 |
Rv3810 pirG |
cell surface protein | 684 | 684 ctx | cooccurence:671 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 707 | 680 | coexpression:669 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 707 | 680 | coexpression:669 |
Rv3707c hyp |
hypothetical protein | 620 | 621 ctx | cooccurence:617 |
Rv0518 hyp |
hypothetical protein | 625 | 608 ctx | cooccurence:590 |
Rv0273c |
transcriptional regulator | 598 | 598 ctx | cooccurence:598 |
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
- Foldseek vs AFDB-SwissProt: Lipid III flippase, TM 0.78, E 1e-8
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
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_218147.1)
- 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
COG2244 - Curated reference: UniProt P9WKX9 (SwissProt, reviewed; 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 —
69 functional partner(s); context anchor
Rv3632 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003847|Rv3630| MAVGAAAVTEVGDTASPVGSSGASGGAIASGSVARVGTATAVTALCGYAVIYLAARNLAPNGFSVFGVFWGAFGLVTGAANGLLQETTREVRSLGYLDVSADGRRTHPLRVSGMVGLGSLVVIAGSSPLWSGRVFAEARWLSVALLSIGLAGFCLHATLLGMLAGTNRWTQYGALMVADAVIRVVVAAATFVIGWQLVGFIWATVAGSVAWLIMLMTSPPTRAAARLMTPGATATFLRGAAHSIIAAGASAILVMGFPVLLKLTSNELGAQGGVVILAVTLTRAPLLVPLTAMQGNLIAHFVDERTERIRALIAPAALIGGVGAVGMLAAGVVGPWIMRVAFGSEYQSSSALLAWLTAAAVAIAMLTLTGAAAVAAALHRAYSLGWVGATVGSGLLLLLPLSLETRTVVALLCGPLVGIGVHLVALARTDE