cysC Resolved · high auto-curated
H37Rv Rv1286 · MTBC0 mtbc0_001376 ·
614 aa · 1447890–1449734 (+) ·
RefSeq NP_215802.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenylyl-sulfate kinase |
|---|---|
| MTBC0 PGAP re-annotation | adenylyl-sulfate kinase |
| Revised (this work) | Adenylyl-sulfate kinase. Pfam: GTP_EFTU (PF00009.34), GTP-eEF1A_C (PF22594.3), APS_kinase (PF01583.27), AAA_33 (PF13671.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNM5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional enzyme CysN/CysC [Includes: Sulfate adenylyltransferase subunit 1 |
| EC (curated) |
EC 2.7.1.25, EC 2.7.7.4
|
| Curated function | With CysD 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..; FUNCTION: APS kinase catalyzes the synthesis of activated sulfate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | cysN |
| eggNOG description | Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. CysN NodQ subfamily |
| Orthologous group | COG0529 |
| EC number |
EC 2.7.1.25, EC 2.7.7.4
|
| KEGG orthology |
K00955, K00956
|
| KEGG pathways |
map00230, map00261, map00450, map00920, map01100, map01120, map01130
|
| KEGG modules |
M00176, M00596
|
| Gene Ontology (55) |
GO:0000103, GO:0003674, GO:0003824, GO:0004020, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006790, GO:0006793 +43 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 | 0.471 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 11 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 |
|---|---|---|---|---|
GTP_EFTU | PF00009.34 | 2.2e-40 | 5–188 | Elongation factor Tu GTP binding domain |
GTP-eEF1A_C | PF22594.3 | 4.0e-28 | 314–414 | GTP-eEF1A C-terminal domain-like |
APS_kinase | PF01583.27 | 1.9e-66 | 442–593 | Adenylylsulphate kinase |
AAA_33 | PF13671.13 | 1.2e-06 | 446–560 | AAA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cysD (sulfate adenylyltransferase subunit 2), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2400c subI |
sulfate ABC transporter substrate-binding lipoprotein SubI | 999 | 1000 | coexpression:998 database:900 textmining:765 |
Rv1285 cysD |
sulfate adenylyltransferase subunit 2 | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:998 experimental:999 database:900 textmining:947 |
Rv2399c cysT |
sulfate ABC transporter permease CysT | 999 | 1000 | coexpression:999 database:900 textmining:487 |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 999 | 1000 ctx | cooccurence:653 coexpression:984 experimental:999 database:900 textmining:637 |
Rv2398c cysW |
sulfate ABC transporter permease CysW | 999 | 1000 | coexpression:999 database:900 textmining:905 |
Rv2397c cysA1 |
sulfate ABC transporter ATP-binding protein CysA | 999 | 999 | coexpression:984 database:900 textmining:418 |
Rv2391 sirA |
sulfite reductase | 996 | 993 ctx | cooccurence:464 coexpression:985 textmining:515 |
Rv2064 cobG |
precorrin-3B synthase | 992 | 987 | coexpression:985 textmining:418 |
Rv1859 modC |
molybdenum ABC transporter ATP-binding protein ModC | 991 | 987 | coexpression:984 textmining:418 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 990 | 963 ctx | neighborhood:544 coexpression:908 textmining:745 |
Rv2131c cysQ |
3'(2'),5'-bisphosphate nucleotidase CysQ | 982 | 963 | database:900 textmining:554 |
Rv2837c nrnA |
bifunctional oligoribonuclease/PAP phosphatase NrnA | 911 | 911 | database:900 |
Rv2613c |
AP-4-A phosphorylase | 903 | 904 | database:900 |
Rv1287 |
HTH-type transcriptional regulator | 867 | 853 ctx | neighborhood:807 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 946 | 831 ctx | neighborhood:544 coexpression:645 textmining:694 |
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: adenylyl-sulfate kinase
- MTBC0 PGAP product: adenylyl-sulfate kinase
- Pfam (hmmscan --cut_ga): GTP_EFTU PF00009.34 (E=2e-40), GTP-eEF1A_C PF22594.3 (E=4e-28), APS_kinase PF01583.27 (E=2e-66), AAA_33 PF13671.13 (E=1e-06)
- (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_215802.1)
- Domains: Pfam-A via hmmscan --cut_ga — GTP_EFTU (PF00009.34), GTP-eEF1A_C (PF22594.3), APS_kinase (PF01583.27), AAA_33 (PF13671.13)
- 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
COG0529 - Curated reference: UniProt P9WNM5 (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 —
109 functional partner(s); context anchor
cysD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001376|Rv1286|cysC MTTLLRLATAGSVDDGKSTLIGRLLYDSKAVMEDQWASVEQTSKDRGHDYTDLALVTDGLRAEREQGITIDVAYRYFATPKRKFIIADTPGHIQYTRNMVTGASTAQLVIVLVDARHGLLEQSRRHAFLASLLGIRHLVLAVNKMDLLGWDQEKFDAIRDEFHAFAARLDVQDVTSIPISALHGDNVVTKSDQTPWYEGPSLLSHLEDVYIAGDRNMVDVRFPVQYVIRPHTLEHQDHRSYAGTVASGVMRSGDEVVVLPIGKTTRITAIDGPNGPVAEAFPPMAVSVRLADDIDISRGDMIARTHNQPRITQEFDATVCWMADNAVLEPGRDYVVKHTTRTVRARIAGLDYRLDVNTLHRDKTATALKLNELGRVSLRTQVPLLLDEYTRNASTGSFILIDPDTNGTVAAGMVLRDVSARTPSPNTVRHRSLVTAQDRPPRGKTVWFTGLSGSGKSSVAMLVERKLLEKGISAYVLDGDNLRHGLNADLGFSMADRAENLRRLSHVATLLADCGHLVLVPAISPLAEHRALARKVHADAGIDFFEVFCDTPLQDCERRDPKGLYAKARAGEITHFTGIDSPYQRPKNPDLRLTPDRSIDEQAQEVIDLLESSS