cysK2 Resolved · high auto-curated
H37Rv Rv0848 · MTBC0 - ·
372 aa · 944938–946056 (+) ·
RefSeq YP_177762.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cysteine synthase CysK |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cysteine synthase CysK. 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 |
Q79FV4
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | S-sulfocysteine synthase |
| EC (curated) |
EC 2.5.1.65, EC 2.8.5.1
|
| Curated function | Catalyzes the synthesis of S-sulfocysteine, utilizing O-phosphoserine (OPS) and thiosulfate as substrates. To a lesser extent, can also use sulfide as donor substrate, producing L-cysteine. CysK2 thus provides a third metabolic route to cysteine, either directly using sulfide as donor or indirectly via S-sulfocysteine. S-sulfocysteine might also act as a signaling molecule triggering additional responses in redox defense in the pathogen upon exposure to reactive oxygen species during intracellular survival or dormancy. Cannot utilize thiocarboxylated CysO as a sulfur donor and O-acetylserine (. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | cysK2 |
| eggNOG description | PFAM Pyridoxal-5'-phosphate-dependent enzyme, beta subunit |
| 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
|
| Gene Ontology (69) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0004124, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737 +57 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 | 1.415 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (283) · clonal |
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 | 3.7e-52 | 31–315 | Pyridoxal-phosphate dependent enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0849 (MFS-type transporter), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0849 |
MFS-type transporter | 999 | 995 ctx | neighborhood:881 cooccurence:735 coexpression:862 textmining:810 |
Rv0850 |
Rv0850, (MTV043.43), len: 110 aa. Putative transposase (fragment), similar in part to others e.g. Q45144|Q4514 transposable element IS31831 | 994 | 962 ctx | neighborhood:801 coexpression:819 textmining:860 |
Rv3684 |
lyase | 936 | 937 | database:900 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 944 | 926 | database:900 |
Rv0884c serC |
phosphoserine aminotransferase | 913 | 906 | database:900 |
Rv0847 lpqS |
lipoprotein LpqS | 964 | 901 ctx | neighborhood:512 coexpression:806 textmining:652 |
Rv0846c mmcO |
oxidase | 951 | 901 | coexpression:846 textmining:534 |
Rv2963 |
integral membrane protein | 880 | 841 | coexpression:841 |
Rv1286 cysC |
adenylyl-sulfate kinase | 908 | 785 | coexpression:756 textmining:590 |
Rv2335 cysE |
serine acetyltransferase | 837 | 750 | coexpression:475 |
Rv1079 metB |
cystathionine gamma-synthase | 650 | 613 | coexpression:464 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 592 | 551 | coexpression:467 |
Rv2398c cysW |
sulfate ABC transporter permease CysW | 748 | 431 | coexpression:412 textmining:576 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 555 | 428 | coexpression:409 |
Rv2397c cysA1 |
sulfate ABC transporter ATP-binding protein CysA | 461 | 428 | coexpression:410 |
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 synthase CysK
- Pfam (hmmscan --cut_ga): PALP PF00291.32 (E=4e-52)
- (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_177762.1)
- 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 Q79FV4 (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 —
42 functional partner(s); context anchor
Rv0849 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0848|cysK2 MRSRQTRDRYRLLPEGYQVTPGRNRHPGTMVGNTPVLWIPELSGTSDPDRGFWAKLEGFNPGGMKDRPALYMVECARARGDIAPGAAIVESTGGTLGLGLALAGKVYRHPVTLVTDPGLEPIIARMLTAYGAGVDMVTQPHPVGGWQQARKDRVAQLMAEYPGAWNPNQYGNPDNVGAYRSLALELVAQLGRIDVLVCSVGTGGHSAGVARVLREFNPDMRLIGVDTIGSTIFGQPASNRLMRGLGSSIYPRNVDYRAFDEVHWVAPPEAVWACRSLAATHYASGGWSVGAVALVAGWAARNLPADTTIAAVFPDGPQRYFDTIYNDAYCNEHELLGGQPPTEPDEIASPLDAVVTRWTRSTTVIDPTQVVS