nrp Resolved · high auto-curated
H37Rv Rv0101 · MTBC0 mtbc0_000110 ·
2512 aa · 110164–117702 (+) ·
RefSeq NP_214615.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | peptide synthetase Nrp |
|---|---|
| MTBC0 PGAP re-annotation | non-ribosomal peptide synthetase Nrp |
| Revised (this work) | Non-ribosomal peptide synthetase Nrp. Pfam: Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Epimerase (PF01370.28), NAD_binding_4 (PF07993.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
Q10896
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Isonitrile lipopeptide synthase |
| EC (curated) |
EC 2.3.1.-, EC 6.2.1.-
|
| Curated function | Nonribosomal peptide synthetase (NRPS) involved in the biosynthesis of a unique class of isonitrile lipopeptides (INLPs) that seem to function as virulence factors in M.tuberculosis and to play a role in metal acquisition. Catalyzes the final step in the pathway, i.e. the condensation of a (3R)-3-isocyanyl-fatty acyl-[ACP] to both amino groups of a lysine, producing isonitrile lipopeptides (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Peptide synthetase |
| Orthologous group | COG1020 |
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 | 0.419 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 30 synonymous, 35 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 |
|---|---|---|---|---|
Condensation | PF00668.26 | 2.0e-86 | 1023–1475 | Condensation domain |
AMP-binding | PF00501.35 | 1.6e-71 | 1499–1832 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.6e-07 | 1890–1965 | AMP-binding enzyme C-terminal domain |
PP-binding | PF00550.32 | 1.0e-13 | 1992–2055 | Phosphopantetheine attachment site |
Epimerase | PF01370.28 | 1.4e-07 | 2110–2317 | NAD dependent epimerase/dehydratase family |
NAD_binding_4 | PF07993.19 | 2.7e-63 | 2112–2372 | Male sterility protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks13 (polyketide synthase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 998 | 997 ctx | neighborhood:544 coexpression:983 experimental:473 textmining:586 |
Rv2383c mbtB |
phenyloxazoline synthase | 997 | 993 ctx | neighborhood:544 coexpression:979 textmining:647 |
Rv0099 fadD10 |
fatty-acid--CoA ligase FadD10 | 991 | 989 ctx | neighborhood:882 coexpression:876 |
Rv1527c pks5 |
polyketide synthase | 994 | 986 ctx | neighborhood:544 cooccurence:529 coexpression:794 experimental:721 textmining:590 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 994 | 986 ctx | neighborhood:544 cooccurence:535 coexpression:794 experimental:721 textmining:590 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 994 | 986 ctx | neighborhood:544 cooccurence:531 coexpression:794 experimental:721 textmining:617 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 994 | 985 ctx | neighborhood:544 cooccurence:503 coexpression:794 experimental:721 textmining:616 |
Rv0100 hyp |
hypothetical protein | 996 | 983 ctx | neighborhood:882 coexpression:860 textmining:803 |
Rv2048c pks12 |
polyketide synthase | 994 | 983 ctx | neighborhood:544 cooccurence:444 coexpression:794 experimental:721 textmining:661 |
Rv0097 |
oxidoreductase | 993 | 976 ctx | neighborhood:804 coexpression:864 textmining:724 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 985 | 972 ctx | neighborhood:527 cooccurence:563 coexpression:768 experimental:473 textmining:501 |
Rv0098 fcoT |
fatty acyl CoA thioesterase FcoT | 994 | 971 ctx | neighborhood:800 coexpression:860 textmining:807 |
Rv2946c pks1 |
polyketide synthase | 984 | 960 ctx | neighborhood:544 coexpression:768 experimental:473 textmining:616 |
Rv0096 PPE1 |
PPE family protein PPE1 | 993 | 959 ctx | neighborhood:719 coexpression:859 textmining:838 |
Rv1661 pks7 |
polyketide synthase | 975 | 959 ctx | cooccurence:498 coexpression:773 experimental:473 textmining:424 |
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: peptide synthetase Nrp
- MTBC0 PGAP product: non-ribosomal peptide synthetase Nrp
- Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=2e-86), AMP-binding PF00501.35 (E=2e-71), AMP-binding_C PF13193.13 (E=2e-07), PP-binding PF00550.32 (E=1e-13), Epimerase PF01370.28 (E=1e-07), NAD_binding_4 PF07993.19 (E=3e-63)
- (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_214615.1)
- Domains: Pfam-A via hmmscan --cut_ga — Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Epimerase (PF01370.28), NAD_binding_4 (PF07993.19)
- 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
COG1020 - Curated reference: UniProt Q10896 (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 —
110 functional partner(s); context anchor
pks13 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000110|Rv0101|nrp MHRVRLSRSQRNLYNGVRQDNNPALYLIGKSYRFRRLELARFLAALHATVLDNPVQLCVLENSGADYPDLVPRLRFGDIVRVGSADEHLQSTWCSGILGKPLVRHTVHTDPNGYVTGLDVHTHHILLDGGATGTIEADLARYLTTDPAGETPSVGAGLAKLREAHRRETAKVEESRGRLSAVVQRELADEAYHGGHGHSVSDAPGTAAKGVLHESATICGNAFDAILTLSEAQRVPLNVLVAAAAVAVDASLRQNTETLLVHTVDNRFGDSDLNVATCLVNSVAQTVRFPPFASVSDVVRTLDRGYVKAVRRRWLREEHYRRMYLAINRTSHVEALTLNFIREPCAPGLRPFLSEVPIATDIGPVEGMTVASVLDEEQRTLNLAIWNRADLPACKTHPKVAERIAAALESMAAMWDRPIAMIVNDWFGIGPDGTRCQGDWPARQPSTPAWFLDSARGVHQFLGRRRFVYPWVAWLVQRGAAPGDVLVFTDDDTDKTIDLLIACHLAGCGYSVCDTADEISVRTNAITEHGDGILVTVVDVAATQLAVVGHDELRKVVDERVTQVTHDALLATKTAYIMPTSGTTGQPKLVRISHGSLAVFCDAISRAYGWGAHDTVLQCAPLTSDISVEEIFGGAACGARLVRSAAMKTGDLAALVDDLVARETTIVDLPTAVWQLLCADGDAIDAIGRSRLRQIVIGGEAIRCSAVDKWLESAASQGISLLSSYGPTEATVVATFLPIVCDQTTMDGALLRLGRPILPNTVFLAFGEVVIVGDLVADGYLGIDGDGFGTVTAADGSRRRAFATGDRVTVDAEGFPVFSGRKDAVVKISGKRVDIAEVTRRIAEDPAVSDVAVELHSGSLGVWFKSQRTREGEQDAAAATRIRLVLVSLGVSSFFVVGVPNIPRKPNGKIDSDNLPRLPQWSAAGLNTAETGQRAAGLSQIWSRQLGRAIGPDSSLLGEGIGSLDLIRILPETRRYLGWRLSLLDLIGADTAANLADYAPTPDAPTGEDRFRPLVAAQRPAAIPLSFAQRRLWFLDQLQRPAPVYNMAVALRLRGYLDTEALGAAVADVVGRHESLRTVFPAVDGVPRQLVIEARRADLGCDIVDATAWPADRLQRAIEEAARHSFDLATEIPLRTWLFRIADDEHVLVAVAHHIAADGWSVAPLTADLSAAYASRCAGRAPDWAPLPVQYVDYTLWQREILGDLDDSDSPIAAQLAYWENALAGMPERLRLPTARPYPPVADQRGASLVVDWPASVQQQVRRIARQHNATSFMVVAAGLAVLLSKLSGSPDVAVGFPIAGRSDPALDNLVGFFVNTLVLRVNLAGDPSFAELLGQVRARSLAAYENQDVPFEVLVDRLKPTRALTHHPLIQVMLAWQDNPVGQLNLGDLQATPMPIDTRTARMDLVFSLAERFSEGSEPAGIGGAVEYRTDVFEAQAIDVLIERLRKVLVAVAAAPERTVSSIDALDGTERARLDEWGNRAVLTAPAPTPVSIPQMLAAQVARIPEAEAVCCGDASMTYRELDEASNRLAHRLAGCGAGPGECVALLFERCAPAVVAMVAVLKTGAAYLPIDPANPPPRVAFMLGDAVPVAAVTTAGLRSRLAGHDLPIIDVVDALAAYPGTPPPMPAAVNLAYILYTSGTTGEPKGVGITHRNVTRLFASLPARLSAAQVWSQCHSYGFDASAWEIWGALLGGGRLVIVPESVAASPNDFHGLLVAEHVSVLTQTPAAVAMLPTQGLESVALVVAGEACPAALVDRWAPGRVMLNAYGPTETTICAAISAPLRPGSGMPPIGVPVSGAALFVLDSWLRPVPAGVAGELYIAGAGVGVGYWRRAGLTASRFVACPFGGSGARMYRTGDLVCWRADGQLEFLGRTDDQVKIRGYRIELGEVATALAELAGVGQAVVIAREDRPGDKRLVGYATEIAPGAVDPAGLRAQLAQRLPGYLVPAAVVVIDALPLTVNGKLDHRALPAPEYGDTNGYRAPAGPVEKTVAGIFARVLGLERVGVDDSFFELGGDSLAAMRVIAAINTTLNADLPVRALLHASSTRGLSQLLGRDARPTSDPRLVSVHGDNPTEVHASDLTLDRFIDADTLATAVNLPGPSPELRTVLLTGATGFLGRYLVLELLRRLDVDGRLICLVRAESDEDARRRLEKTFDSGDPELLRHFKELAADRLEVVAGDKSEPDLGLDQPMWRRLAETVDLIVDSAAMVNAFPYHELFGPNVAGTAELIRIALTTKLKPFTYVSTADVGAAIEPSAFTEDADIRVISPTRTVDGGWAGGYGTSKWAGEVLLREANDLCALPVAVFRCGMILADTSYAGQLNMSDWVTRMVLSLMATGIAPRSFYEPDSEGNRQRAHFDGLPVTFVAEAIAVLGARVAGSSLAGFATYHVMNPHDDGIGLDEYVDWLIEAGYPIRRIDDFAEWLQRFEASLGALPDRQRRHSVLPMLLASNSQRLQPLKPTRGCSAPTDRFRAAVRAAKVGSDKDNPDIPHVSAPTIINYVTNLQLLGLL