mmpL2 Resolved · high auto-curated
H37Rv Rv0507 · MTBC0 mtbc0_000535 ·
968 aa · 600656–603562 (+) ·
RefSeq NP_215021.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane transport protein MmpL2 |
|---|---|
| MTBC0 PGAP re-annotation | RND transporter MmpL2 |
| Revised (this work) | RND transporter MmpL2. Pfam: MMPL (PF03176.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJV7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable transport protein MmpL2 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mmpL2 |
| eggNOG description | transport protein |
| Orthologous group | COG1033 |
| KEGG orthology |
K06994
|
| Gene Ontology (17) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044110, GO:0044116, GO:0044117, GO:0044119 +5 more
|
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 | 0.649 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 18 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.75% of strains (1092) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
MMPL | PF03176.22 | 8.8e-120 | 54–382 | MMPL family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmpS2 (membrane protein MmpS2), high confidence from genomic context alone (score 883 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0506 mmpS2 |
membrane protein MmpS2 | 900 | 883 ctx | neighborhood:881 |
Rv0508 hyp |
hypothetical protein | 867 | 867 ctx | neighborhood:866 |
Rv1598c hyp |
hypothetical protein | 700 | 701 ctx | cooccurence:699 |
Rv1303 hyp |
hypothetical protein | 667 | 667 ctx | cooccurence:666 |
Rv0509 hemA |
glutamyl-tRNA reductase | 637 | 637 ctx | neighborhood:637 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 630 | 630 ctx | cooccurence:630 |
Rv0510 hemC |
porphobilinogen deaminase | 620 | 620 ctx | neighborhood:618 |
Rv2945c lppX |
lipoprotein LppX | 652 | 616 ctx | cooccurence:615 |
Rv1145 mmpL13a |
transmembrane transport protein | 596 | 581 ctx | cooccurence:578 |
Rv0128 |
transmembrane protein | 580 | 580 ctx | cooccurence:580 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 537 | 536 ctx | neighborhood:534 |
Rv0256c PPE2 |
PPE family protein PPE2 | 526 | 526 ctx | cooccurence:526 |
Rv0505c serB1 |
phosphoserine phosphatase SerB | 515 | 516 ctx | neighborhood:511 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 502 | 503 ctx | cooccurence:485 |
Rv1278 hyp |
hypothetical protein | 479 | 480 ctx | cooccurence:478 |
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
- Legacy H37Rv annotation: transmembrane transport protein MmpL2
- MTBC0 PGAP product: RND transporter MmpL2
- Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=9e-120)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_215021.1)
- Domains: Pfam-A via hmmscan --cut_ga — MMPL (PF03176.22)
- 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
COG1033 - Curated reference: UniProt P9WJV7 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
43 functional partner(s); context anchor
mmpS2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000535|Rv0507|mmpL2 MSERHAALTSLPPILPRLIRRFAVVIVLLWLGFTAFVNLAVPQLEVVGKAHSVSMSPSDAASIQAIKRVGQVFGEFDSDNAVTIVLEGDQPLGGDAHRFYSDLMRKLSADTRHVAHIQDFWGDPLTAAGSQSADDRAAYVVVYLVGNNETEAYDSVHAVRHMVDTTPPPHGVKAYVTGPAALNADQAEAGDKSIAKVTAITSMVIAAMLLVIYRSVITAVLVLIMVGIDLGAIRGFIALLADHNIFSLSTFATNLLVLMAIAASTDYAIFMLGRYHESRYAGEDRETAFYTMFHGTAHVILGSGLTIAGAMYCLSFARLPYFETLGAPIAIGMLVAVLAALTLGPAVLTVGSFFKLFDPKRRMNTRRWRRVGTAIVRWPGPVLAATCLVASIGLLALPSYRTTYDLRKFMPASMPSNVGDAAAGRHFSRARLNPEVLLIETDHDMRNPVDMLVLDKVAKNIYHSPGIEQVKAITRPLGTTIKHTSIPFIISMQGVNSSEQMEFMKDRIDDILVQVAAMNTSIETMHRMYALMGEVIDNTVDMDHLTHDMSDITATLRDHLADFEDFFRPIRSYFYWEKHCFDVPLCWSIRSIFDMFDSVDQLSEKLEYLVKDMDILITLLPQMRAQMPPMISAMTTMRDMMLIWHGTLGAFYKQQERNNKDPGAMGRVFDAAQIDDSFYLPQSAFENPDFKRGLKMFLSPDGKAARFVIALEGDPATPEGISRVEPIKREAREAIKGTPLQGAAIYLGGTAATFKDIREGARYDLLIAGVAAISLILIIMMIITRSVVAAVVIVGTVVLSMGASFGLSVLVWQDILGIELYWMVLAMSVILLLAVGSDYNLLLISRLKEEIGAGLNTGIIRAMAGTGGVVTAAGMVFAVTMSLFVFSDLRIIGQIGTTIGLGLLFDTLVVRSFMTPSIAALLGRWFWWPLRVRPRPASQMLRPFAPRRLVRALLLPSGQHPSATGAHE