cysD Family assigned · medium auto-curated
H37Rv Rv1285 · MTBC0 mtbc0_001375 ·
332 aa · 1446892–1447890 (+) ·
RefSeq NP_215801.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | sulfate adenylyltransferase subunit 2 |
|---|---|
| MTBC0 PGAP re-annotation | sulfate adenylyltransferase subunit CysD |
| Revised (this work) | Sulfate adenylyltransferase subunit CysD. 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 |
P9WIK1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sulfate adenylyltransferase subunit 2 |
| EC (curated) |
EC 2.7.7.4
|
| Curated function | With CysN forms the ATP sulfurylase (ATPS) that catalyzes the adenylation of sulfate producing adenosine 5'-phosphosulfate (APS) and diphosphate, the first enzymatic step in sulfur assimilation pathway. APS synthesis involves the formation of a high-energy phosphoric-sulfuric acid anhydride bond driven by GTP hydrolysis by CysN coupled to ATP hydrolysis by CysD. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | cysD |
| eggNOG description | Sulfate adenylyltransferase subunit 2 |
| Orthologous group | COG0175 |
| EC number |
EC 2.7.7.4
|
| KEGG orthology |
K00957
|
| KEGG pathways |
map00230, map00261, map00450, map00920, map01100, map01120, map01130
|
| KEGG modules |
M00176, M00596
|
| Gene Ontology (42) |
GO:0000103, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006790, GO:0006950, GO:0006979, GO:0007154, GO:0008150, GO:0008152 +30 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 | 0.656 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
PAPS_reduct | PF01507.26 | 5.3e-47 | 63–285 | 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 | neighborhood:881 cooccurence:774 coexpression:998 experimental:999 database:900 textmining:947 |
Rv2399c cysT |
sulfate ABC transporter permease CysT | 974 | 972 | coexpression:675 database:900 |
Rv2400c subI |
sulfate ABC transporter substrate-binding lipoprotein SubI | 982 | 966 | coexpression:657 database:900 textmining:496 |
Rv2398c cysW |
sulfate ABC transporter permease CysW | 976 | 966 | coexpression:656 database:900 |
Rv2397c cysA1 |
sulfate ABC transporter ATP-binding protein CysA | 970 | 950 | coexpression:506 database:900 textmining:432 |
Rv2131c cysQ |
3'(2'),5'-bisphosphate nucleotidase CysQ | 940 | 930 | database:900 |
Rv2837c nrnA |
bifunctional oligoribonuclease/PAP phosphatase NrnA | 902 | 903 | database:900 |
Rv2613c |
AP-4-A phosphorylase | 902 | 903 | database:900 |
Rv2391 sirA |
sulfite reductase | 953 | 888 ctx | cooccurence:606 coexpression:660 textmining:602 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 906 | 861 | coexpression:808 |
Rv1287 |
HTH-type transcriptional regulator | 861 | 852 ctx | neighborhood:807 |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 934 | 749 ctx | cooccurence:688 textmining:748 |
Rv2064 cobG |
precorrin-3B synthase | 698 | 670 | coexpression:659 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 691 | 572 | coexpression:512 |
Rv1284 canA |
beta-carbonic anhydrase | 586 | 565 ctx | neighborhood:548 |
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: sulfate adenylyltransferase subunit 2
- MTBC0 PGAP product: sulfate adenylyltransferase subunit CysD
- Pfam (hmmscan --cut_ga): PAPS_reduct PF01507.26 (E=5e-47)
- (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_215801.1)
- 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 P9WIK1 (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 —
39 functional partner(s); context anchor
cysC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001375|Rv1285|cysD MAITINMVNPTGFIRYEDVEQEAMTSDVTVGPAPGQYQLSHLRLLEAEAIHVIREVAAEFERPVLLFSGGKDSIVMLHLALKAFRPGRLPFPVMHVDTGHNFDEVIATRDELVAAAGVRLVVASVQDDIDAGRVVETIPSRNPIQTVTLLRAIRENQFDAAFGGARRDEEKARAKERVFSFRDEFGQWDPKAQRPELWNLYNGRHHKGEHIRVFPLSNWTEFDIWSYIGAEQVRLPSIYFAHRRKVFQRDGMLLAVHRHMQPRADEPVFEATVRFRTVGDVTCTGCVESSASTVAEVIAETAVARLTERGATRADDRISEAGMEDRKRQGYF