irtA Family assigned · medium auto-curated
H37Rv Rv1348 · MTBC0 mtbc0_001446 ·
859 aa · 1523749–1526328 (+) ·
RefSeq NP_215864.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron ABC transporter ATP-binding protein/permease IrtA |
|---|---|
| MTBC0 PGAP re-annotation | iron ABC transporter ATP-binding protein/permease IrtA |
| Revised (this work) | Iron ABC transporter ATP-binding protein/permease IrtA. Pfam: FAD_binding_9 (PF08021.18), SIP (PF04954.19), ABC_membrane (PF00664.29), ABC_tran (PF00005.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQJ9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycobactin import ATP-binding/permease protein IrtA |
| EC (curated) |
EC 7.2.2.-
|
| Curated function | Part of the ABC transporter complex IrtAB involved in the import of iron-bound mycobactin (Fe-MBT) and carboxymycobactin (Fe-cMBT) (By similarity). Mycobactins are then reduced by the siderophore interaction domain to facilitate iron release in the bacterial cell (By similarity). Transmembrane domains (TMD) form a pore in the membrane and the ATP-binding domain (NBD) is responsible for energy generation (By similarity). Required for replication in human macrophages and in mouse lungs. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolismV Defense mechanisms
|
|---|---|
| Preferred name | irtA |
| eggNOG description | ABC transporter |
| Orthologous group | COG1132 |
| KEGG orthology |
K06147, K14698
|
| KEGG pathways |
map02010
|
| Gene Ontology (88) |
GO:0000041, GO:0000166, GO:0003674, GO:0005215, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006810, GO:0006811, GO:0006812, GO:0006826 +76 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 | 0.288 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 7 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 |
|---|---|---|---|---|
FAD_binding_9 | PF08021.18 | 2.1e-10 | 60–113 | Siderophore-interacting FAD-binding domain |
SIP | PF04954.19 | 2.4e-26 | 130–241 | Siderophore-interacting protein |
ABC_membrane | PF00664.29 | 7.9e-16 | 294–553 | ABC transporter transmembrane region |
ABC_tran | PF00005.34 | 9.4e-29 | 627–774 | ABC transporter |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: irtB (iron ABC transporter ATP-binding protein/permease IrtB), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1349 irtB |
iron ABC transporter ATP-binding protein/permease IrtB | 999 | 998 ctx | neighborhood:833 coexpression:861 database:900 textmining:623 |
Rv2383c mbtB |
phenyloxazoline synthase | 979 | 919 ctx | neighborhood:544 coexpression:757 textmining:756 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 956 | 896 | coexpression:853 textmining:596 |
Rv2386c mbtI |
salicylate synthase | 909 | 796 | coexpression:751 textmining:577 |
Rv3402c hyp |
hypothetical protein | 831 | 787 | coexpression:780 |
Rv0435c |
ATPase | 773 | 745 | database:528 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 855 | 716 | database:528 textmining:511 |
Rv0350 dnaK |
chaperone protein DnaK | 730 | 702 ctx | cooccurence:471 |
Rv1350 fabG2 |
3-oxoacyl-ACP reductase FabG | 692 | 678 ctx | neighborhood:506 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA | 705 | 663 | database:528 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 749 | 662 | database:528 |
Rv2688c |
antibiotic ABC transporter ATP-binding protein | 667 | 647 | database:536 |
Rv3846 sodA |
superoxide dismutase | 663 | 643 | experimental:412 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 767 | 638 ctx | cooccurence:546 |
Rv1687c |
ABC transporter ATP-binding protein | 654 | 632 | database:536 |
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: iron ABC transporter ATP-binding protein/permease IrtA
- MTBC0 PGAP product: iron ABC transporter ATP-binding protein/permease IrtA
- Pfam (hmmscan --cut_ga): FAD_binding_9 PF08021.18 (E=2e-10), SIP PF04954.19 (E=2e-26), ABC_membrane PF00664.29 (E=8e-16), ABC_tran PF00005.34 (E=9e-29)
- (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_215864.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_9 (PF08021.18), SIP (PF04954.19), ABC_membrane (PF00664.29), ABC_tran (PF00005.34)
- 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
COG1132 - Curated reference: UniProt P9WQJ9 (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 —
151 functional partner(s); context anchor
irtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001446|Rv1348|irtA MARGLQGVMLRSFGARDHTATVIETISIAPHFVRVRMVSPTLFQDAEAEPAAWLRFWFPDPNGSNTEFQRAYTISEADPAAGRFAVDVVLHDPAGPASSWARTVKPGATIAVMSLMGSSRFDVPEEQPAGYLLIGDSASIPGMNGIIETVPNDVPIEMYLEQHDDNDTLIPLAKHPRLRVRWVMRRDEKSLAEAIENRDWSDWYAWATPEAAALKCVRVRLRDEFGFPKSEIHAQAYWNAGRAMGTHRATEPAATEPEVGAAPQPESAVPAPARGSWRAQAASRLLAPLKLPLVLSGVLAALVTLAQLAPFVLLVELSRLLVSGAGAHRLFTVGFAAVGLLGTGALLAAALTLWLHVIDARFARALRLRLLSKLSRLPLGWFTSRGSGSIKKLVTDDTLALHYLVTHAVPDAVAAVVAPVGVLVYLFVVDWRVALVLFGPVLVYLTITSSLTIQSGPRIVQAQRWAEKMNGEAGSYLEGQPVIRVFGAASSSFRRRLDEYIGFLVAWQRPLAGKKTLMDLATRPATFLWLIAATGTLLVATHRMDPVNLLPFMFLGTTFGARLLGIAYGLGGLRTGLLAARHLQVTLDETELAVREHPREPLDGEAPATVVFDHVTFGYRPGVPVIQDVSLTLRPGTVTALVGPSGSGKSTLATLLARFHDVERGAIRVGGQDIRSLAADELYTRVGFVLQEAQLVHGTAAENIALAVPDAPAEQVQVAAREAQIHDRVLRLPDGYDTVLGANSGLSGGERQRLTIARAILGDTPVLILDEATAFADPESEYLVQQALNRLTRDRTVLVIAHRLHTITRADQIVVLDHGRIVERGTHEELLAAGGRYCRLWDTGQGSRVAVAAAQDGTR