nicT Family assigned · medium auto-curated
H37Rv Rv2856 · MTBC0 mtbc0_003035 ·
372 aa · 3187350–3188468 (+) ·
RefSeq NP_217372.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nickel-transport integral membrane protein NicT |
|---|---|
| MTBC0 PGAP re-annotation | HoxN/HupN/NixA family nickel/cobalt transporter |
| Revised (this work) | HoxN/HupN/NixA family nickel/cobalt transporter. Pfam: NicO (PF03824.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YEJ7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nickel transporter NicT |
| Curated function | Involved in nickel uptake. In addition, acts as a drug efflux pump and contributes to moderate tolerance towards different classes of antibiotics, including fluoroquinolones, aminoglycosides and the anti-TB drug isoniazid, with a preference for fluoroquinolones. The drug efflux function is probably dependent on proton motive force (pmf) or ion gradient, and might be facilitated by the presence of Ni(2+) ions. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | nicT |
| eggNOG description | Belongs to the NiCoT transporter (TC 2.A.52) family |
| Orthologous group | COG2042 |
| KEGG orthology |
K07241
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 4 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 |
|---|---|---|---|---|
NicO | PF03824.23 | 2.3e-109 | 64–353 | High-affinity nickel-transport protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mtr (mycothione reductase), medium confidence from genomic context alone (score 662 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2855 mtr |
mycothione reductase | 661 | 662 ctx | neighborhood:657 |
Rv2854 hyp |
hypothetical protein | 648 | 648 ctx | neighborhood:643 |
Rv2349c plcC |
phospholipase C | 474 | 475 ctx | cooccurence:467 |
Rv1902c nanT |
sialic acid-transport integral membrane protein NanT | 471 | 472 ctx | cooccurence:459 |
Rv2351c plcA |
membrane-associated phospholipase A | 466 | 467 ctx | cooccurence:465 |
Rv2350c plcB |
membrane-associated phospholipase B | 465 | 465 ctx | cooccurence:462 |
Rv3310 sapM |
acid phosphatase | 461 | 461 ctx | cooccurence:461 |
Rv1755c plcD |
Rv1755c, (MT1799, MTCY28.21c), len: 280 aa. Probable plcD, phospholipase C 4 (fragment) (see citations below),highly similar to C-terminus o | 460 | 461 ctx | cooccurence:455 |
Rv2853 PE_PGRS48 |
PE-PGRS family protein PE_PGRS48 | 440 | 441 ctx | neighborhood:441 |
Rv1762c hyp |
hypothetical protein | 401 | 401 ctx | cooccurence:401 |
Rv2059 hyp |
hypothetical protein | 642 | 295 | textmining:514 |
Rv2025c |
cation efflux system protein | 409 | 241 | |
Rv2060 |
integral membrane protein | 699 | 174 | textmining:651 |
Rv0106 hyp |
hypothetical protein | 551 | 114 | textmining:515 |
Rv2359 zur |
zinc uptake regulation protein | 647 | 87 | textmining:630 |
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: nickel-transport integral membrane protein NicT
- MTBC0 PGAP product: HoxN/HupN/NixA family nickel/cobalt transporter
- Pfam (hmmscan --cut_ga): NicO PF03824.23 (E=2e-109)
- (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_217372.1)
- Domains: Pfam-A via hmmscan --cut_ga — NicO (PF03824.23)
- 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
COG2042 - Curated reference: UniProt I6YEJ7 (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 —
20 functional partner(s); context anchor
mtr - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003035|Rv2856|nicT MASSQLDRQRSRSAKMNRALTAAEWWRLGLMFAVIVALHLVGWLTVTLLVEPARLSLGGKAFGIGVGLTAYTLGLRHAFDADHIAAIDNTTRKLMSDGHRPLAVGFFFSLGHSTVVFGLAVMLVTGLKAIVGPVENDSSTLHHYTGLIGTSISGAFLYLIGILNVIVLVGIVRVFAHLRRGDYDEAELEQQLDNRGLLIRFLGRFTKSLTKSWHMYPVGFLFGLGFDTATEIALLVLAGTSAAAGLPWYAILCLPVLFAAGMCLLDTIDGSFMNFAYGWAFSSPVRKIYYNITVTGLSVAVALLIGSVELLGLIANQLGWQGPFWDWLGGLDLNTVGFVVVAMFALTWAIALLVWHYGRVEERWTPAPDRTT