mmpL1 Resolved · high auto-curated

H37Rv Rv0402c · MTBC0 mtbc0_000422 · 958 aa · 483719–486595 (-) · RefSeq NP_214916.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane transport protein MmpL1
MTBC0 PGAP re-annotationRND transporter MmpL1
Revised (this work)RND transporter MmpL1. 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 P9WJV9 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable transport protein MmpL1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred namemmpL1
eggNOG descriptionconserved transmembrane transport protein
Orthologous groupCOG0642
KEGG orthology K06994
Gene Ontology (9) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 1.157 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 16 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 15.05% of strains (21852) · convergent

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)

PfamAccessioni-EvalueResiduesDescription
MMPLPF03176.22 9.2e-12153–381 MMPL family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: mmpS1 (membrane protein MmpS1), high confidence from genomic context alone (score 976 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0403c mmpS1 membrane protein MmpS1 975 976 ctx neighborhood:881 coexpression:805
Rv1598c hyp hypothetical protein 691 691 ctx cooccurence:691
Rv1303 hyp hypothetical protein 632 632 ctx cooccurence:632
Rv0290 eccD3 ESX-3 secretion system protein EccD 597 597 ctx cooccurence:596
Rv0128 transmembrane protein 551 551 ctx cooccurence:550
Rv1145 mmpL13a transmembrane transport protein 684 537 ctx cooccurence:534
Rv0404 fadD30 long-chain-fatty-acid--AMP ligase FadD30 528 528
Rv2945c lppX lipoprotein LppX 559 507 ctx cooccurence:504
Rv0466 hyp hypothetical protein 504 505 ctx cooccurence:503
Rv0523c hyp hypothetical protein 489 490 ctx cooccurence:489
Rv0283 eccB3 ESX-3 secretion system protein EccB3 472 472 ctx cooccurence:453
Rv0405 pks6 membrane bound polyketide synthase 539 470
Rv1278 hyp hypothetical protein 451 451 ctx cooccurence:451
Rv0184 hyp hypothetical protein 439 440 ctx cooccurence:439
Rv0282 eccA3 ESX-3 secretion system protein EccA 417 417 ctx cooccurence:414

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 MmpL1
  • MTBC0 PGAP product: RND transporter MmpL1
  • Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=9e-121)
  • (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_214916.1)
  • 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 COG0642
  • Curated reference: UniProt P9WJV9 (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 — 25 functional partner(s); context anchor mmpS1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000422|Rv0402c|mmpL1
MRSQRLAGHLSAAARTIHALSLPIILFWVALTIVVNVVAPQLQSVARTHSVALGPHDAPSLIAMKRIGKDFQQFDSDTTAMVLLEGQEKLGDEAHRFYDVLVTKLSQDTTHVQHIENFWGDPLTAAGSQSADGKAAYVQLNLTGDQGGSQANESVAAVQRIVDSVPPPPGIKAYVTGPGPLGADRVVYGDRSLHTITGISIAVIAIMLFIAYRSLSAALIMLLTVGLELLAVRGIISTFAVNDLMGLSTFTVNVLVALTIAASTDYIIFLVGRYQEARATGQNREAAYYTMFGGTAHVVLASGLTVAGAMYCLGFTRLPYFNTLASPCAIGLVTVMLASLTLAPAIIAVASRFGLFDPKRATTKRRWRRIGTVVVRWPGPVLAATLLIALIGLLALPKYQTNYNERYYIPSAAPSNIGYLASDRHFPQARMEPEVLMVEADHDLRNPTDMLILDRIAKTVFHTPGIARVQSITRPLGAPIDHSSIPFQLGMQSTMTIENLQNLKDRVADLSTLTDQLQRMIDITQRTQELTRQLTDATHDMNAHTRQMRDNANELRDRIADFDDFWRPLRSFTYWERHCFDIPICWSMRSLLNSMDNVDKLTEDLANLTDDTERMDTTQRQLLAQLDPTIATMQTVKDLAQTLTSAFSGLVTQMEDMTRNATVMGRTFDAANNDDSFYLPPEAFQNPDFQRGLKLFLSPDGTCARFVITHRGDPASAEGISHIDPIMQAADEAVKGTPLQAASIYLAGTSSTYKDIHEGTLYDVMIAVVASLCLIFIIMLGITRSVVASAVIVGTVALSLGSAFGLSVLIWQHILHMPLHWLVLPMAIIVMLAVGSDYNLLLIARFQEEIGAGLKTGMIRAMAGTGRVVTIAGLVFAFTMGSMVASDLRVVGQIGTTIMIGLLFDTLVVRSYMTPALATLLGRWFWWPRRVDRLARQPQVLGPRRTTALSAERAALLQ