cysM Resolved · high auto-curated
H37Rv Rv1336 · MTBC0 mtbc0_001433 ·
323 aa · 1514096–1515067 (+) ·
RefSeq NP_215852.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | O-phosphoserine sulfhydrylase |
|---|---|
| MTBC0 PGAP re-annotation | O-phosphoserine sulfhydrylase |
| Revised (this work) | O-phosphoserine sulfhydrylase. Pfam: PALP (PF00291.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP53
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | O-phosphoserine sulfhydrylase |
| EC (curated) |
EC 2.5.1.113
|
| Curated function | Catalyzes the formation of a covalent CysO-cysteine adduct via a sulfur transfer, using the thiocarboxylated sulfur carrier protein CysO-COSH as sulfur donor and O-phospho-L-serine (OPS) as sulfur acceptor. Can also use sodium sulfide as sulfur donor in vitro, albeit with less efficiency, but not thiosulfate or thio-nitro-benzoate. O-acetylserine (OAS) is a very poor substrate in comparison with OPS. May be of particular importance for cysteine biosynthesis in the persistent phase of M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | cysM |
| eggNOG description | cysteine |
| Orthologous group | COG0031 |
| EC number |
EC 2.5.1.113
|
| KEGG orthology |
K21148
|
| KEGG pathways |
map04122
|
| Gene Ontology (59) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520 +47 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 | 1.44 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 2 nonsense, 2 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.77% of strains (1121) · convergent |
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 |
|---|---|---|---|---|
PALP | PF00291.32 | 9.2e-67 | 8–293 | Pyridoxal-phosphate dependent enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cysO (sulfur carrier protein CysO), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1335 cysO |
sulfur carrier protein CysO | 999 | 1000 ctx | neighborhood:876 coexpression:808 experimental:999 textmining:901 |
Rv1334 mec |
[CysO | 991 | 992 ctx | neighborhood:847 cooccurence:439 coexpression:809 database:500 |
Rv1338 murI |
glutamate racemase | 979 | 973 ctx | neighborhood:881 coexpression:785 |
Rv1337 |
integral membrane protein | 960 | 905 ctx | neighborhood:881 textmining:594 |
Rv1332 |
transcriptional regulator | 875 | 855 ctx | neighborhood:829 |
Rv1333 |
hydrolase | 854 | 854 ctx | neighborhood:847 |
Rv1339 hyp |
hypothetical protein | 844 | 845 ctx | neighborhood:843 |
Rv1340 rphA |
ribonuclease PH | 835 | 835 ctx | neighborhood:825 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 837 | 830 ctx | neighborhood:829 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 813 | 813 ctx | neighborhood:780 |
Rv2335 cysE |
serine acetyltransferase | 947 | 795 | coexpression:495 textmining:753 |
Rv1286 cysC |
adenylyl-sulfate kinase | 909 | 784 | coexpression:755 textmining:600 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 749 | 749 ctx | neighborhood:747 |
Rv1329c dinG |
ATP-dependent helicase DinG | 725 | 725 ctx | neighborhood:719 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 927 | 617 | database:500 textmining:820 |
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: O-phosphoserine sulfhydrylase
- MTBC0 PGAP product: O-phosphoserine sulfhydrylase
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=9e-67)
- (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_215852.1)
- Domains: Pfam-A via hmmscan --cut_ga — PALP (PF00291.32)
- 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
COG0031 - Curated reference: UniProt P9WP53 (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 —
48 functional partner(s); context anchor
cysO - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001433|Rv1336|cysM MTRYDSLLQALGNTPLVGLQRLSPRWDDGRDGPHVRLWAKLEDRNPTGSIKDRPAVRMIEQAEADGLLRPGATILEPTSGNTGISLAMAARLKGYRLICVMPENTSVERRQLLELYGAQIIFSAAEGGSNTAVATAKELAATNPSWVMLYQYGNPANTDSHYCGTGPELLADLPEITHFVAGLGTTGTLMGTGRFLREHVANVKIVAAEPRYGEGVYALRNMDEGFVPELYDPEILTARYSVGAVDAVRRTRELVHTEGIFAGISTGAVLHAALGVGAGALAAGERADIALVVADAGWKYLSTGAYAGSLDDAETALEGQLWA