cysS1 Resolved · high auto-curated

H37Rv Rv3580c · MTBC0 - · 469 aa · 4022394–4023803 (-) · RefSeq YP_177992.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cysteine--tRNA ligase
MTBC0 PGAP re-annotation
Revised (this work)Cysteine--tRNA ligase. Pfam: tRNA-synt_1e (PF01406.26), tRNA-synt_1g (PF09334.18), DALR_2 (PF09190.18).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WFW1 SwissProt · reviewed · Evidence at protein level
UniProt nameCysteine--tRNA ligase
EC (curated) EC 6.1.1.16

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
Preferred namecysS
eggNOG descriptionBelongs to the class-I aminoacyl-tRNA synthetase family
Orthologous groupCOG0215
EC number EC 6.1.1.16
KEGG orthology K01883
KEGG pathways map00970
KEGG modules M00359, M00360
Gene Ontology (77) GO:0000166, GO:0003674, GO:0003824, GO:0004812, GO:0004817, GO:0005488, GO:0005524, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +65 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 0.325 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
tRNA-synt_1ePF01406.26 7.8e-13220–314 tRNA synthetases class I (C) catalytic domain
tRNA-synt_1gPF09334.18 1.1e-05257–310 tRNA synthetases class I (M)
DALR_2PF09190.18 1.2e-06342–394 DALR domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: rlmB (23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB), high confidence from genomic context alone (score 939 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3579c rlmB 23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB 947 939 ctx neighborhood:882 coexpression:443
Rv2335 cysE serine acetyltransferase 920 855 ctx fusion:477 coexpression:718 textmining:479
Rv3581c ispF 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 801 802 ctx neighborhood:799
Rv3582c ispD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 800 800 ctx neighborhood:799
Rv3834c serS serine--tRNA ligase 851 789 ctx cooccurence:716
Rv3583c carD RNA polymerase-binding transcription factor CarD 788 789 ctx neighborhood:788
Rv2614c thrS threonine--tRNA ligase 904 733 ctx cooccurence:676 textmining:657
Rv1976c hyp hypothetical protein 702 696 coexpression:679
Rv2334 cysK1 O-acetylserine sulfhydrylase 702 639 ctx fusion:578
Rv0073 glutamine ABC transporter ATP-binding protein 652 639 ctx cooccurence:519
Rv2564 glnQ glutamine ABC transporter ATP-binding protein 632 619 ctx cooccurence:498
Rv1077 cbs cystathionine beta-synthase 650 598 ctx fusion:491
Rv2448c valS valine--tRNA ligase 972 597 coexpression:419 textmining:934
Rv1086 (2Z,6E)-farnesyl diphosphate synthase 616 594 ctx cooccurence:589
Rv2555c alaS alanine--tRNA ligase 640 592 coexpression:409

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): cysteine--tRNA ligase
  • Pfam (hmmscan --cut_ga): tRNA-synt_1e PF01406.26 (E=8e-132), tRNA-synt_1g PF09334.18 (E=1e-05), DALR_2 PF09190.18 (E=1e-06)
  • (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 YP_177992.1)
  • Domains: Pfam-A via hmmscan --cut_ga — tRNA-synt_1e (PF01406.26), tRNA-synt_1g (PF09334.18), DALR_2 (PF09190.18)
  • 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 COG0215
  • Curated reference: UniProt P9WFW1 (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 — 68 functional partner(s); context anchor rlmB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3580c|cysS1
MTDRARLRLHDTAAGVVRDFVPLRPGHVSIYLCGATVQGLPHIGHVRSGVAFDILRRWLLARGYDVAFIRNVTDIEDKILAKAAAAGRPWWEWAATHERAFTAAYDALDVLPPSAEPRATGHITQMIEMIERLIQAGHAYTGGGDVYFDVLSYPEYGQLSGHKIDDVHQGEGVAAGKRDQRDFTLWKGEKPGEPSWPTPWGRGRPGWHLECSAMARSYLGPEFDIHCGGMDLVFPHHENEIAQSRAAGDGFARYWLHNGWVTMGGEKMSKSLGNVLSMPAMLQRVRPAELRYYLGSAHYRSMLEFSETAMQDAVKAYVGLEDFLHRVRTRVGAVCPGDPTPRFAEALDDDLSVPIALAEIHHVRAEGNRALDAGDHDGALRSASAIRAMMGILGCDPLDQRWESRDETSAALAAVDVLVQAELQNREKAREQRNWALADEIRGRLKRAGIEVTDTADGPQWSLLGGDTK