iunH Resolved · high auto-curated

H37Rv Rv3393 · MTBC0 mtbc0_003605 · 308 aa · 3833900–3834826 (+) · RefSeq NP_217910.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nucleoside hydrolase
MTBC0 PGAP re-annotationnucleoside hydrolase IunH
Revised (this work)Nucleoside hydrolase IunH. Pfam: IU_nuc_hydro (PF01156.25).

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

Curated reference (UniProt)

UniProt O50418 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable nucleoside hydrolase IunH

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred nameiunH
eggNOG descriptionnucleoside hydrolase
Orthologous groupCOG1957
EC number EC 3.2.2.1
KEGG orthology K01239, K01250
KEGG pathways map00230, map00760, map01100

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 1.445 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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)

PfamAccessioni-EvalueResiduesDescription
IU_nuc_hydroPF01156.25 7.1e-794–295 Inosine-uridine preferring nucleoside hydrolase

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

Closest characterised functional partner: rbsK (ribokinase RbsK), high confidence from genomic context alone (score 794 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3307 deoD purine nucleoside phosphorylase 963 917 database:900 textmining:583
Rv2202c adoK adenosine kinase 925 915 database:900
Rv2043c pncA pyrazinamidase/nicotinamidase PncA 928 913 database:900
Rv3313c add adenosine deaminase 918 910 database:900
Rv1151c cobB NAD-dependent protein deacylase 909 904 database:900
Rv2584c apt adenine phosphoribosyltransferase 982 903 database:900 textmining:832
Rv3624c hpt hypoxanthine-guanine phosphoribosyltransferase 967 901 database:900 textmining:688
Rv0212c nadR transcriptional regulator NadR 903 900 database:900
Rv2436 rbsK ribokinase RbsK 887 794 ctx cooccurence:726 textmining:478
Rv3315c cdd cytidine deaminase 620 575 database:500
Rv3392c cmaA1 cyclopropane mycolic acid synthase CmaA 573 573 ctx neighborhood:567
Rv3752c tadA cytidine/deoxycytidylate deaminase 575 559 database:500
Rv1629 polA DNA polymerase I 528 216 textmining:423
Rv0787A purS hyp hypothetical protein 709 164 textmining:667
Rv0994 moeA1 molybdopterin molybdenumtransferase 1 599 163 textmining:541

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: nucleoside hydrolase
  • MTBC0 PGAP product: nucleoside hydrolase IunH
  • Pfam (hmmscan --cut_ga): IU_nuc_hydro PF01156.25 (E=7e-79)
  • (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_217910.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IU_nuc_hydro (PF01156.25)
  • 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 COG1957
  • Curated reference: UniProt O50418 (TrEMBL, unreviewed; 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 — 37 functional partner(s); context anchor rbsK
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003605|Rv3393|iunH
MSVVFADVDTGIDDALAVIYLLASPDADLVGIASTGGNIAVGQVCANNLSLLELCGAADIPVSKGADEPLGGRWPDHPKFHGPKGIGYAELPASNRRLTDYDATTAWIAAAHSHAGDLIGLVTGPLTNLALALRAEPALPRLLRRLVIMGGMFDGQPITEWNIRVDPEAASEVFTAWAGQRQLPIVCGLDLTRRVAMTPDILARLASVCGSSPVMRVIEDALRFYFESHEARGHGYLAYMHDPLAAAVAMDPELLTTRTATVDVDPTGATVTDWSGKRNPNARIGMSVDPAVFFDRFVERIGRFARRT