cysQ Resolved · high auto-curated

H37Rv Rv2131c · MTBC0 mtbc0_002264 · 267 aa · 2419780–2420583 (-) · RefSeq NP_216647.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3'(2'),5'-bisphosphate nucleotidase CysQ
MTBC0 PGAP re-annotation3'(2')%2C5'-bisphosphate nucleotidase CysQ
Revised (this work)3'(2')%2C5'-bisphosphate nucleotidase CysQ. Pfam: Inositol_P (PF00459.31).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WKJ1 SwissProt · reviewed · Evidence at protein level
UniProt name3'-phosphoadenosine 5'-phosphate phosphatase
EC (curated) EC 3.1.3.11, EC 3.1.3.25, EC 3.1.3.7
Curated functionPhosphatase with a broad specificity. Its primary physiological function is to dephosphorylate 3'-phosphoadenosine 5'-phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Thus, plays a role in mycobacterial sulfur metabolism, since it can serve as a key regulator of the sulfate assimilation pathway by controlling the pools of PAP and PAPS in the cell. To a lesser extent, is also able to hydrolyze inositol 1-phosphate (I-1-P), fructose 1,6-bisphosphate (FBP) (to fructose 6-phosphate (F-6-P)) and AMP in vitro, but this might not be significant in vivo. Glucose-1-phosphate (G-1-P), p.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namecysQ
eggNOG descriptionInositol monophosphatase
Orthologous groupCOG1218
EC number EC 3.1.3.7
KEGG orthology K01082
KEGG pathways map00920, map01100, map01120, map01130
Gene Ontology (64) GO:0000103, GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006139, GO:0006163, GO:0006725 +52 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 0.122 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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)

PfamAccessioni-EvalueResiduesDescription
Inositol_PPF00459.31 1.1e-2545–240 Inositol monophosphatase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: mshC (cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase), high confidence from genomic context alone (score 814 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1286 cysC adenylyl-sulfate kinase 982 963 database:900 textmining:554
Rv1285 cysD sulfate adenylyltransferase subunit 2 940 930 database:900
Rv2392 cysH phosphoadenosine phosphosulfate reductase 968 911 database:900 textmining:659
Rv2837c nrnA bifunctional oligoribonuclease/PAP phosphatase NrnA 963 901 database:900 textmining:644
Rv2130c mshC cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase 823 814 ctx neighborhood:805
Rv2129c oxidoreductase 609 609 ctx neighborhood:555
Rv2132 hyp hypothetical protein 572 572 ctx neighborhood:572
Rv2764c thyA thymidylate synthase ThyA 566 567 coexpression:461
Rv2134c hyp hypothetical protein 563 563 ctx neighborhood:544
Rv0363c fba fructose-bisphosphate aldolase 561 562 database:500
Rv2136c uppP undecaprenyl-diphosphatase 560 561 ctx neighborhood:544
Rv2133c hyp hypothetical protein 550 550 ctx neighborhood:544
Rv2135c hyp hypothetical protein 573 549 ctx neighborhood:544
Rv2137c hyp hypothetical protein 545 546 ctx neighborhood:544
Rv0946c pgi glucose-6-phosphate isomerase 550 533 database:500

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: 3'(2'),5'-bisphosphate nucleotidase CysQ
  • MTBC0 PGAP product: 3'(2')%2C5'-bisphosphate nucleotidase CysQ
  • Pfam (hmmscan --cut_ga): Inositol_P PF00459.31 (E=1e-25)
  • (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_216647.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Inositol_P (PF00459.31)
  • 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 COG1218
  • Curated reference: UniProt P9WKJ1 (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 — 34 functional partner(s); context anchor mshC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002264|Rv2131c|cysQ
MVSPAAPDLTDDLTDAELAADLAADAGKLLLQVRAEIGFDQPWTLGEAGDRQANSLLLRRLQAERPGDAVLSEEAHDDLARLKSDRVWIIDPLDGTREFSTPGRDDWAVHIALWRRSSNGQPEITDAAVALPARGNVVYRTDTVTSGAAPAGVPGTLRIAVSATRPPAVLHRIRQTLAIQPVSIGSAGAKAMAVIDGYVDAYLHAGGQWEWDSAAPAGVMLAAGMHASRLDGSPLRYNQLDPYLPDLLMCRAEVAPILLGAIADAWR