hisS Resolved · high auto-curated
H37Rv Rv2580c · MTBC0 mtbc0_002747 ·
423 aa · 2928365–2929636 (-) ·
RefSeq NP_217096.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | histidine--tRNA ligase |
|---|---|
| MTBC0 PGAP re-annotation | histidine--tRNA ligase |
| Revised (this work) | Histidine--tRNA ligase. Pfam: tRNA-synt_His (PF13393.12), tRNA-synt_2b (PF00587.31), 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 |
P9WFV5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Histidine--tRNA ligase |
| EC (curated) |
EC 6.1.1.21
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
|---|---|
| Preferred name | hisS |
| eggNOG description | histidyl-tRNA synthetase |
| Orthologous group | COG0124 |
| EC number |
EC 6.1.1.21
|
| KEGG orthology |
K01892
|
| 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 | 0.288 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
tRNA-synt_His | PF13393.12 | 7.2e-37 | 12–310 | Histidyl-tRNA synthetase |
tRNA-synt_2b | PF00587.31 | 1.3e-14 | 70–298 | tRNA synthetase class II core domain (G, H, P, S and T) |
HGTP_anticodon | PF03129.26 | 1.6e-16 | 330–418 | Anticodon binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2581c (glyoxalase II), high confidence from genomic context alone (score 888 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2581c |
glyoxalase II | 888 | 888 ctx | neighborhood:882 |
Rv2572c aspS |
aspartate--tRNA ligase | 877 | 836 | coexpression:808 |
Rv2121c hisG |
ATP phosphoribosyltransferase | 864 | 822 | experimental:790 |
Rv2448c valS |
valine--tRNA ligase | 967 | 678 | coexpression:426 textmining:903 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 712 | 676 | coexpression:649 |
Rv2582 ppiB |
peptidyl-prolyl cis-trans isomerase B | 661 | 648 ctx | neighborhood:644 |
Rv2555c alaS |
alanine--tRNA ligase | 712 | 624 | coexpression:517 |
Rv2614c thrS |
threonine--tRNA ligase | 960 | 588 | coexpression:427 textmining:908 |
Rv3396c guaA |
GMP synthase | 773 | 580 | coexpression:422 textmining:484 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 624 | 573 ctx | cooccurence:454 |
Rv3598c lysS |
lysine--tRNA ligase | 738 | 565 | textmining:423 |
Rv1640c lysX |
bifunctional lysine--tRNA ligase/phosphatidylglycerol lysyltransferase | 678 | 547 | |
Rv1292 argS |
arginine--tRNA ligase | 942 | 543 | coexpression:403 textmining:879 |
Rv2540c aroF |
chorismate synthase | 514 | 515 | coexpression:498 |
Rv3580c cysS1 |
cysteine--tRNA ligase | 841 | 501 | coexpression:423 textmining:696 |
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: histidine--tRNA ligase
- MTBC0 PGAP product: histidine--tRNA ligase
- Pfam (hmmscan --cut_ga): tRNA-synt_His PF13393.12 (E=7e-37), tRNA-synt_2b PF00587.31 (E=1e-14), HGTP_anticodon PF03129.26 (E=2e-16)
- (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_217096.1)
- Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_His (PF13393.12), tRNA-synt_2b (PF00587.31), 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
COG0124 - Curated reference: UniProt P9WFV5 (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 —
95 functional partner(s); context anchor
Rv2581c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002747|Rv2580c|hisS MTEFSSFSAPKGVPDYVPPDSAQFVAVRDGLLAAARQAGYSHIELPIFEDTALFARGVGESTDVVSKEMYTFADRGDRSVTLRPEGTAGVVRAVIEHGLDRGALPVKLCYAGPFFRYERPQAGRYRQLQQVGVEAIGVDDPALDAEVIAIADAGFRSLGLDGFRLEITSLGDESCRPQYRELLQEFLFGLDLDEDTRRRAGINPLRVLDDKRPELRAMTASAPVLLDHLSDVAKQHFDTVLAHLDALGVPYVINPRMVRGLDYYTKTAFEFVHDGLGAQSGIGGGGRYDGLMHQLGGQDLSGIGFGLGVDRTVLALRAEGKTAGDSARCDVFGVPLGEAAKLRLAVLAGRLRAAGVRVDLAYGDRGLKGAMRAAARSGARVALVAGDRDIEAGTVAVKDLTTGEQVSVSMDSVVAEVISRLAG