cysH Resolved · high auto-curated
H37Rv Rv2392 · MTBC0 mtbc0_002545 ·
254 aa · 2710560–2711324 (+) ·
RefSeq NP_216908.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phosphoadenosine phosphosulfate reductase |
|---|---|
| MTBC0 PGAP re-annotation | phosphoadenylyl-sulfate reductase |
| Revised (this work) | Phosphoadenylyl-sulfate reductase. Pfam: PAPS_reduct (PF01507.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIK3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Adenosine 5'-phosphosulfate reductase |
| EC (curated) |
EC 1.8.4.10
|
| Curated function | Catalyzes the formation of sulfite from adenosine 5'-phosphosulfate (APS) using thioredoxin as an electron donor. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismH Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cysH |
| eggNOG description | Belongs to the PAPS reductase family. CysH subfamily |
| Orthologous group | COG0175 |
| EC number |
EC 1.8.4.10, EC 1.8.4.8
|
| KEGG orthology |
K00390
|
| KEGG pathways |
map00920, map01100, map01120
|
| KEGG modules |
M00176
|
| Gene Ontology (58) |
GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0004604, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +46 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 | 0.342 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 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 |
|---|---|---|---|---|
PAPS_reduct | PF01507.26 | 1.0e-52 | 60–228 | Phosphoadenosine phosphosulfate reductase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cysC (adenylyl-sulfate kinase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1286 cysC |
adenylyl-sulfate kinase | 999 | 1000 ctx | cooccurence:653 coexpression:984 experimental:999 database:900 textmining:637 |
Rv2391 sirA |
sulfite reductase | 999 | 1000 ctx | neighborhood:882 fusion:497 cooccurence:767 coexpression:971 database:900 textmining:845 |
Rv2393 che1 |
ferrochelatase | 990 | 989 ctx | neighborhood:881 coexpression:891 |
Rv2394 ggtB |
gamma-glutamyltranspeptidase precursor GgtB | 957 | 935 ctx | neighborhood:653 coexpression:819 |
Rv2131c cysQ |
3'(2'),5'-bisphosphate nucleotidase CysQ | 968 | 911 | database:900 textmining:659 |
Rv0815c cysA2 |
thiosulfate sulfurtransferase CysA | 926 | 906 | database:900 |
Rv3283 sseA |
thiosulfate sulfurtransferase SseA | 909 | 904 | database:900 |
Rv2291 sseB |
thiosulfate sulfurtransferase SseB | 909 | 904 | database:900 |
Rv2837c nrnA |
bifunctional oligoribonuclease/PAP phosphatase NrnA | 903 | 903 | database:900 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 932 | 899 ctx | cooccurence:408 coexpression:808 |
Rv3106 fprA |
NADPH-ferredoxin reductase FprA | 836 | 812 | coexpression:766 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 887 | 781 | coexpression:769 textmining:508 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 934 | 749 ctx | cooccurence:688 textmining:748 |
Rv2399c cysT |
sulfate ABC transporter permease CysT | 759 | 730 | coexpression:677 |
Rv2064 cobG |
precorrin-3B synthase | 744 | 720 | coexpression:663 |
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: phosphoadenosine phosphosulfate reductase
- MTBC0 PGAP product: phosphoadenylyl-sulfate reductase
- Pfam (hmmscan --cut_ga): PAPS_reduct PF01507.26 (E=1e-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 NP_216908.1)
- Domains: Pfam-A via hmmscan --cut_ga — PAPS_reduct (PF01507.26)
- 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
COG0175 - Curated reference: UniProt P9WIK3 (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 —
44 functional partner(s); context anchor
cysC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002545|Rv2392|cysH MSGETTRLTEPQLRELAARGAAELDGATATDMLRWTDETFGDIGGAGGGVSGHRGWTTCNYVVASNMADAVLVDLAAKVRPGVPVIFLDTGYHFVETIGTRDAIESVYDVRVLNVTPEHTVAEQDELLGKDLFARNPHECCRLRKVVPLGKTLRGYSAWVTGLRRVDAPTRANAPLVSFDETFKLVKVNPLAAWTDQDVQEYIADNDVLVNPLVREGYPSIGCAPCTAKPAEGADPRSGRWQGLAKTECGLHAS