iscS Family assigned · medium auto-curated
H37Rv Rv3025c · MTBC0 mtbc0_003216 ·
393 aa · 3405195–3406376 (-) ·
RefSeq NP_217541.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cysteine desulfurase |
|---|---|
| MTBC0 PGAP re-annotation | cysteine desulfurase family protein |
| Revised (this work) | Cysteine desulfurase family protein. Pfam: Aminotran_5 (PF00266.26), Beta_elim_lyase (PF01212.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ71
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | IscS-like cysteine desulfurase |
| EC (curated) |
EC 2.8.1.7
|
| Curated function | Catalyzes the removal of elemental sulfur from cysteine to produce alanine (Probable). Participates in the biosynthesis of metalloclusters by providing the inorganic sulfur required for Fe-S core formation. One acceptor is Whib3, on which this enzyme assembles a 4Fe-4S cluster. It can use both L-cysteine and L-selenocysteine as substrates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | iscS |
| eggNOG description | Cysteine desulfurase |
| Orthologous group | COG1104 |
| EC number |
EC 2.8.1.7
|
| KEGG orthology |
K04487
|
| KEGG pathways |
map00730, map01100, map04122
|
| Gene Ontology (19) |
GO:0003674, GO:0003824, GO:0006790, GO:0008150, GO:0008152, GO:0009987, GO:0016043, GO:0016226, GO:0016740, GO:0016782, GO:0016783, GO:0022607 +7 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 | 0.044 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 1 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 |
|---|---|---|---|---|
Aminotran_5 | PF00266.26 | 1.6e-62 | 3–369 | Aminotransferase class-V |
Beta_elim_lyase | PF01212.28 | 1.9e-07 | 60–180 | Beta-eliminating lyase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: trmU (tRNA-specific 2-thiouridylase), high confidence from genomic context alone (score 939 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1465 |
nitrogen fixation related protein | 998 | 998 | coexpression:857 experimental:928 database:844 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 981 | 976 | database:960 |
Rv3116 moeB2 |
molybdenum cofactor biosynthesis protein MoeB | 981 | 975 | database:960 |
Rv3024c trmU |
tRNA-specific 2-thiouridylase | 953 | 939 ctx | neighborhood:881 coexpression:406 |
Rv2291 sseB |
thiosulfate sulfurtransferase SseB | 923 | 915 | database:900 |
Rv0815c cysA2 |
thiosulfate sulfurtransferase CysA | 922 | 915 | database:900 |
Rv3283 sseA |
thiosulfate sulfurtransferase SseA | 922 | 915 | database:900 |
Rv1937 |
oxygenase | 907 | 870 | experimental:422 database:621 |
Rv3554 fdxB |
electron transfer protein FdxB | 867 | 848 | experimental:422 database:621 |
Rv3230c |
stearoyl-CoA 9-desaturase electron transfer protein | 855 | 834 | experimental:422 database:621 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 854 | 834 | experimental:422 database:621 |
Rv2776c |
oxidoreductase | 854 | 834 | experimental:422 database:621 |
Rv1287 |
HTH-type transcriptional regulator | 854 | 830 | coexpression:790 |
Rv3027c |
GCN5-like N-acetyltransferase | 776 | 776 ctx | neighborhood:775 |
Rv2204c hyp |
hypothetical protein | 814 | 758 | coexpression:691 |
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: cysteine desulfurase
- MTBC0 PGAP product: cysteine desulfurase family protein
- Pfam (hmmscan --cut_ga): Aminotran_5 PF00266.26 (E=2e-62), Beta_elim_lyase PF01212.28 (E=2e-07)
- (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_217541.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aminotran_5 (PF00266.26), Beta_elim_lyase (PF01212.28)
- 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
COG1104 - Curated reference: UniProt P9WQ71 (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 —
87 functional partner(s); context anchor
trmU - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003216|Rv3025c|iscS MAYLDHAATTPMHPAAIEAMAAVQRTIGNASSLHTSGRSARRRIEEARELIADKLGARPSEVIFTAGGTESDNLAVKGIYWARRDAEPHRRRIVTTEVEHHAVLDSVNWLVEHEGAHVTWLPTAADGSVSATALREALQSHDDVALVSVMWANNEVGTILPIAEMSVVAMEFGVPMHSDAIQAVGQLPLDFGASGLSAMSVAGHKFGGPPGVGALLLRRDVTCVPLMHGGGQERDIRSGTPDVASAVGMATAAQIAVDGLEENSARLRLLRDRLVEGVLAEIDDVCLNGADDPMRLAGNAHFTFRGCEGDALLMLLDANGIECSTGSACTAGVAQPSHVLIAMGVDAASARGSLRLSLGHTSVEADVDAALEVLPGAVARARRAALAAAGASR