Rv3684 Resolved · high auto-curated
H37Rv Rv3684 · MTBC0 - ·
346 aa · 4125439–4126479 (+) ·
RefSeq NP_218201.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | lyase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Lyase. Pfam: PALP (PF00291.32). |
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 |
O69652
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | L-cysteine desulfhydrase Cds1 |
| EC (curated) |
EC 4.4.1.1
|
| Curated function | A cysteine desulfhydrase that generates hydrogen sulfide, H(2)S. The H(2)S produced by this enzyme stimulates respiration in M.tuberculosis, mediated primarily via cytochrome bd with a lesser contribution from cytochrome bc1/aa3. H(2)S modulates the balance between respiration and glycolysis, and also contributes to redox homeostasis. Probably eliminates toxic levels of Cys (which can induce oxidative stress). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | cysK |
| eggNOG description | cysteine synthase |
| Orthologous group | COG0031 |
| EC number |
EC 2.5.1.47
|
| KEGG orthology |
K01738
|
| KEGG pathways |
map00270, map00920, map01100, map01110, map01120, map01130, map01200, map01230
|
| KEGG modules |
M00021
|
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 | 0.34 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 3 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 |
|---|---|---|---|---|
PALP | PF00291.32 | 7.2e-53 | 25–306 | Pyridoxal-phosphate dependent enzyme |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2335 cysE |
serine acetyltransferase | 987 | 966 | coexpression:477 database:900 textmining:646 |
Rv1079 metB |
cystathionine gamma-synthase | 964 | 953 | coexpression:466 database:900 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 956 | 953 | coexpression:467 database:900 |
Rv2391 sirA |
sulfite reductase | 943 | 940 | coexpression:409 database:900 |
Rv0848 cysK2 |
cysteine synthase CysK | 936 | 937 | database:900 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 932 | 920 | database:900 |
Rv0884c serC |
phosphoserine aminotransferase | 920 | 908 | database:900 |
Rv0075 |
aminotransferase | 909 | 905 | database:900 |
Rv2294 |
cystathionine beta-lyase | 908 | 903 | database:900 |
Rv0331 |
dehydrogenase/reductase | 908 | 903 | database:900 |
Rv3248c sahH |
adenosylhomocysteinase | 857 | 843 | database:800 |
Rv1077 cbs |
cystathionine beta-synthase | 847 | 842 | database:800 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 835 | 826 | database:800 |
Rv2213 pepB |
cytosol aminopeptidase | 835 | 826 | database:800 |
Rv2124c metH |
methionine synthase | 869 | 822 | database:800 |
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): lyase
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=7e-53)
- (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_218201.3)
- 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 O69652 (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 — 47 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3684| MIEADARRSADTHLLRYPLPAAWCTDVDVELYLKDETTHITGSLKHRLARSLFLYALCNGWINENTTVVEASSGSTAVSEAYFAALLGLPFIAVMPAATSASKIALIESQGGRCHFVQNSSQVYAEAERVAKETGGHYLDQFTNAERATDWRGNNNIAESIYVQMREEKHPTPEWIVVGAGTGGTSATIGRYIRYRRHATRLCVVDPENSAFFPAYSEGRYDIVMPTSSRIEGIGRPRVEPSFLPGVVDRMVAVPDAASIAAARHVSAVLGRRVGPSTGTNLWGAFGLLAEMVKQGRSGSVVTLLADSGDRYADTYFSDEWVSAQGLDPAGPAAALVEFERSCRWT