omamA Resolved · high
H37Rv Rv0199 · MTBC0 mtbc0_000213 ·
219 aa · 236902–237561 (+) ·
RefSeq NP_214713.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Mce-associated membrane (Mam) protein OmamA (orphaned Mam protein A), an exported virulence factor that stabilises the Mce lipid-transport complexes. RefSeq leaves this locus 'hypothetical protein'; here it is re-annotated from published genetics/cell biology. Rv0199 is required for cholesterol import (a Mce4-dependent process) and stabilises protein components of the Mce1 transporter complex, a role proposed to be analogous to VirB8 in stabilising Type-IV secretion systems (Perkowski 2016). It was independently identified as an exported, intracellular-growth factor (β-lactamase reporter transposon screen; attenuated macrophage growth) (McCann 2011). Experimentally characterised, not a structural prediction. |
Curated reference (UniProt)
| UniProt |
O53650
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BKG3 |
|---|
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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 6 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).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0200 (transmembrane protein), high confidence from genomic context alone (score 885 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0200 |
transmembrane protein | 955 | 885 ctx | neighborhood:882 textmining:622 |
Rv0198c zmp1 |
zinc metalloprotease | 795 | 784 ctx | neighborhood:759 |
Rv2048c pks12 |
polyketide synthase | 764 | 737 | experimental:470 database:508 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 763 | 735 | experimental:470 database:508 |
Rv1527c pks5 |
polyketide synthase | 763 | 735 | experimental:470 database:508 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 763 | 735 | experimental:470 database:508 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 767 | 734 | experimental:470 database:508 |
Rv2267c stf3 hyp |
hypothetical protein | 740 | 730 | experimental:417 database:540 |
Rv1691 hyp |
hypothetical protein | 740 | 730 | experimental:417 database:540 |
Rv3529c hyp |
hypothetical protein | 740 | 729 | experimental:417 database:540 |
Rv1663 pks17 |
polyketide synthase | 737 | 727 | experimental:458 database:508 |
Rv1334 mec |
[CysO | 728 | 718 | experimental:404 database:546 |
Rv1277 hyp |
hypothetical protein | 702 | 703 | experimental:438 database:493 |
Rv3696c glpK |
glycerol kinase | 707 | 695 | database:502 |
Rv1389 gmk |
guanylate kinase | 701 | 689 | experimental:411 database:491 |
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
- RefSeq: hypothetical / exported membrane protein of unknown function
- Mce-associated membrane (Mam) family; renamed OmamA
- Required for cholesterol import (Mce4-dependent); stabilises the Mce1 transporter complex (Perkowski 2016, PMID 26712165)
- Exported protein with a role in intracellular growth; attenuated in macrophages (McCann 2011, PMID 21148733)
- 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_214713.1)
- 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
2BKG3 - Curated reference: UniProt O53650 (TrEMBL, unreviewed; 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 —
242 functional partner(s); context anchor
Rv0200 - Primary literature: Perkowski EF, Miller BK, McCann JR, Sullivan JT, Malik S, Allen IC, Godfrey V, Hayden JD, Braunstein M (2016). An orphaned Mce-associated membrane protein of Mycobacterium tuberculosis is a virulence factor that stabilizes Mce transporters Mol Microbiol 100(1):90-107. doi:10.1111/mmi.13303 PMID:26712165
- Primary literature: McCann JR, McDonough JA, Sullivan JT, Feltcher ME, Braunstein M (2011). Genome-wide identification of Mycobacterium tuberculosis exported proteins with roles in intracellular growth J Bacteriol 193(4):854-61. doi:10.1128/JB.01271-10 PMID:21148733
Ancestral MTBC0 protein sequence
>mtbc0_000213|Rv0199|omamA MPDGEQSQPPAQEDAEDDSRPDAAEAAAAEPKSSAGPMFSTYGIASTLLGVLSVAAVVLGAMIWSAHRDDSGERTYLTRVMLTAAEWTAVLINMNADNIDASLQRLHDGTVGQLNTDFDAVVQPYRQVVEKLRTHSSGRIEAVAIDTVHRELDTQSGAARPVVTTKLPPFATRTDSVLLVATSVSENAGAKPQTVHWNLRLDVSDVDGKLMISRLESIR