proS Resolved · high auto-curated
H37Rv Rv2845c · MTBC0 mtbc0_003024 ·
582 aa · 3171868–3173616 (-) ·
RefSeq NP_217361.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | proline--tRNA ligase |
|---|---|
| MTBC0 PGAP re-annotation | proline--tRNA ligase |
| Revised (this work) | Proline--tRNA ligase. Pfam: tRNA-synt_2b (PF00587.31), tRNA_edit (PF04073.21), HGTP_anticodon (PF03129.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WFT9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Proline--tRNA ligase |
| EC (curated) |
EC 6.1.1.15
|
| Curated function | Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro). As ProRS can inadvertently accommodate and process non-cognate amino acids such as alanine and cysteine, to avoid such errors it has two additional distinct editing activities against alanine. One activity is designated as 'pretransfer' editing and involves the tRNA(Pro)-independent hydrolysis of activated Ala-AMP. The other activity is designated 'posttransfer' editing and involves deacylation of mischarged Ala-tRNA(P. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | proS |
| eggNOG description | Catalyzes the attachment of proline to tRNA(Pro) in a two-step reaction proline is first activated by ATP to form Pro- AMP and then transferred to the acceptor end of tRNA(Pro). As ProRS can inadvertently accommodate and process non-cognate amino acids such as alanine and cysteine, to avoid such errors it has two additional distinct editing activities against alanine. One activity is designated as 'pretransfer' editing and involves the tRNA(Pro)-independent hydrolysis of activated Ala-AMP. The other activity is designated 'posttransfer' editing and involves deacylation of mischarged Ala-tRNA(Pro). The misacylated Cys- tRNA(Pro) is not edited by ProRS |
| Orthologous group | COG0442 |
| EC number |
EC 6.1.1.15
|
| KEGG orthology |
K01881
|
| KEGG pathways |
map00970
|
| KEGG modules |
M00359, M00360
|
| Gene Ontology (10) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, 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 | 0.297 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
tRNA-synt_2b | PF00587.31 | 2.9e-25 | 96–471 | tRNA synthetase class II core domain (G, H, P, S and T) |
tRNA_edit | PF04073.21 | 2.6e-14 | 280–387 | Aminoacyl-tRNA editing domain |
HGTP_anticodon | PF03129.26 | 8.9e-13 | 490–565 | Anticodon binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: efpA (MFS-type transporter EfpA), high confidence from genomic context alone (score 740 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1536 ileS |
isoleucine--tRNA ligase | 993 | 987 | coexpression:763 experimental:875 database:597 textmining:513 |
Rv2992c gltS |
glutamate--tRNA ligase | 972 | 962 | coexpression:434 experimental:852 database:546 |
Rv1292 argS |
arginine--tRNA ligase | 957 | 940 | coexpression:704 experimental:512 database:597 |
Rv1007c metS |
methionine--tRNA ligase | 990 | 907 | coexpression:425 experimental:629 database:571 textmining:900 |
Rv0041 leuS |
leucine--tRNA ligase | 930 | 868 | coexpression:415 experimental:467 database:597 textmining:494 |
Rv1640c lysX |
bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase | 883 | 806 | coexpression:411 experimental:473 textmining:421 |
Rv3598c lysS |
lysine--tRNA ligase | 889 | 803 | coexpression:416 experimental:473 textmining:462 |
Rv3396c guaA |
GMP synthase | 807 | 753 | coexpression:695 |
Rv2846c efpA |
MFS-type transporter EfpA | 740 | 740 ctx | neighborhood:736 |
Rv1699 pyrG |
CTP synthase | 725 | 726 | coexpression:719 |
Rv1087A |
Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT | 700 | 700 | coexpression:647 |
Rv2361c uppS |
decaprenyl diphosphate synthase | 689 | 689 | coexpression:647 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 839 | 682 | coexpression:583 textmining:517 |
Rv0823c dusB |
tRNA-dihydrouridine synthase | 698 | 679 | database:647 |
Rv2462c tig |
trigger factor | 701 | 673 | coexpression:654 |
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: proline--tRNA ligase
- MTBC0 PGAP product: proline--tRNA ligase
- Pfam (hmmscan --cut_ga): tRNA-synt_2b PF00587.31 (E=3e-25), tRNA_edit PF04073.21 (E=3e-14), HGTP_anticodon PF03129.26 (E=9e-13)
- (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_217361.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_2b (PF00587.31), tRNA_edit (PF04073.21), HGTP_anticodon (PF03129.26)
- 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
COG0442 - Curated reference: UniProt P9WFT9 (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 —
73 functional partner(s); context anchor
efpA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003024|Rv2845c|proS MITRMSELFLRTLRDDPADAEVASHKLLIRAGYIRPVAPGLYSWLPLGLRVLRNIERVIRDEMNAIGGQEILFPALLPRAPYETTNRWTQYGDSVFRLKDRRGNDYLLGPTHEELFTLTVKGEYSSYKDFPLTLYQIQTKYRDEARPRAGILRAREFVMKDSYSFDIDAAGLKAAYHAHREAYQRIFDRLQVRYVIVSAVSGAMGGSASEEFLAESPSGEDAFVRCLESGYAANVEAVVTARPDTLPIDGLPEAVVHDTGDTPTIASLVAWANEADLGRTVTAADTLKNVLIKVRQPGGDTELLAIGVPGDREVDDKRLGAALEPADYALLDDDDFAKHPFLVKGYIGPKALRENNVRYLVDPRIVDGTSWITGADQPGRHVVGLVAGRDFTADGTIEAAEVREGDPSPDGAGPLVMARGIEIGHIFQLGSKYTDAFTADVLGEDGKPVRLTMGSYGIGVSRLVAVVAEQHHDELGLRWPSTVAPFDVHLVIANKDAQARAGATALAADLDRLGVEVLLDDRQASPGVKFKDAELLGMPWIVVVGRGWADGVVELRDRFSGQTRELVAGASLATDIAAAVTG