sirA Resolved · high auto-curated
H37Rv Rv2391 · MTBC0 - ·
563 aa · 2684679–2686370 (+) ·
RefSeq NP_216907.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | sulfite reductase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Sulfite reductase. Pfam: NIR_SIR_ferr (PF03460.23), NIR_SIR (PF01077.28). |
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 |
P9WJ03
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sulfite reductase [ferredoxin] |
| EC (curated) |
EC 1.8.7.1
|
| Curated function | Catalyzes the reduction of sulfite to sulfide, a step in the biosynthesis of sulfur-containing amino acids and cofactors. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | sirA |
| eggNOG description | Belongs to the nitrite and sulfite reductase 4Fe-4S domain family |
| Orthologous group | COG0155 |
| EC number |
EC 1.7.7.1, EC 1.8.7.1
|
| KEGG orthology |
K00366, K00392
|
| KEGG pathways |
map00910, map00920, map01100, map01120
|
| KEGG modules |
M00176, M00531
|
| Gene Ontology (59) |
GO:0000096, GO:0000097, GO:0000103, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +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 | 0.43 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 |
|---|---|---|---|---|
NIR_SIR_ferr | PF03460.23 | 6.0e-15 | 100–160 | Nitrite/Sulfite reductase ferredoxin-like half domain |
NIR_SIR | PF01077.28 | 9.6e-42 | 169–322 | Nitrite and sulphite reductase 4Fe-4S domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cysH (phosphoadenosine phosphosulfate reductase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 999 | 1000 ctx | neighborhood:882 fusion:497 cooccurence:767 coexpression:971 database:900 textmining:845 |
Rv1286 cysC |
adenylyl-sulfate kinase | 996 | 993 ctx | cooccurence:464 coexpression:985 textmining:515 |
Rv2393 che1 |
ferrochelatase | 989 | 987 ctx | neighborhood:881 coexpression:871 |
Rv2334 cysK1 |
O-acetylserine sulfhydrylase | 958 | 942 | coexpression:430 database:900 |
Rv3684 |
lyase | 943 | 940 | coexpression:409 database:900 |
Rv1079 metB |
cystathionine gamma-synthase | 965 | 931 | database:900 textmining:518 |
Rv0391 metZ |
O-succinylhomoserine sulfhydrylase | 950 | 931 | database:900 |
Rv2394 ggtB |
gamma-glutamyltranspeptidase precursor GgtB | 960 | 929 ctx | neighborhood:651 coexpression:806 textmining:469 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 967 | 919 ctx | cooccurence:549 coexpression:799 textmining:618 |
Rv0331 |
dehydrogenase/reductase | 923 | 916 | database:900 |
Rv0815c cysA2 |
thiosulfate sulfurtransferase CysA | 914 | 906 | database:900 |
Rv3283 sseA |
thiosulfate sulfurtransferase SseA | 912 | 904 | database:900 |
Rv2291 sseB |
thiosulfate sulfurtransferase SseB | 909 | 904 | database:900 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 953 | 888 ctx | cooccurence:606 coexpression:660 textmining:602 |
Rv3106 fprA |
NADPH-ferredoxin reductase FprA | 839 | 815 | coexpression:770 |
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): sulfite reductase
- Pfam (hmmscan --cut_ga): NIR_SIR_ferr PF03460.23 (E=6e-15), NIR_SIR PF01077.28 (E=1e-41)
- (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_216907.1)
- Domains: Pfam-A via hmmscan --cut_ga — NIR_SIR_ferr (PF03460.23), NIR_SIR (PF01077.28)
- 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
COG0155 - Curated reference: UniProt P9WJ03 (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 —
52 functional partner(s); context anchor
cysH - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2391|sirA MSAKENPQMTTARPAKARNEGQWALGHREPLNANEELKKAGNPLDVRERIENIYAKQGFDSIDKTDLRGRFRWWGLYTQREQGYDGTWTGDDNIDKLEAKYFMMRVRCDGGALSAAALRTLGQISTEFARDTADISDRQNVQYHWIEVENVPEIWRRLDDVGLQTTEACGDCPRVVLGSPLAGESLDEVLDPTWAIEEIVRRYIGKPDFADLPRKYKTAISGLQDVAHEINDVAFIGVNHPEHGPGLDLWVGGGLSTNPMLAQRVGAWVPLGEVPEVWAAVTSVFRDYGYRRLRAKARLKFLIKDWGIAKFREVLETEYLKRPLIDGPAPEPVKHPIDHVGVQRLKNGLNAVGVAPIAGRVSGTILTAVADLMARAGSDRIRFTPYQKLVILDIPDALLDDLIAGLDALGLQSRPSHWRRNLMACSGIEFCKLSFAETRVRAQHLVPELERRLEDINSQLDVPITVNINGCPNSCARIQIADIGFKGQMIDDGHGGSVEGFQVHLGGHLGLDAGFGRKLRQHKVTSDELGDYIDRVVRNFVKHRSEGERFAQWVIRAEEDDLR