hpt Resolved · high auto-curated
H37Rv Rv3624c · MTBC0 mtbc0_003841 ·
216 aa · 4086958–4087608 (-) ·
RefSeq NP_218141.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypoxanthine-guanine phosphoribosyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | hypoxanthine phosphoribosyltransferase |
| Revised (this work) | Hypoxanthine phosphoribosyltransferase. Pfam: Pribosyltran (PF00156.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHQ9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Hypoxanthine-guanine phosphoribosyltransferase |
| EC (curated) |
EC 2.4.2.8
|
| Curated function | Purine salvage pathway enzyme that catalyzes the transfer of the ribosyl-5-phosphate group from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to the N9 position of the 6-oxopurines hypoxanthine and guanine to form the corresponding ribonucleotides IMP (inosine 5'-monophosphate) and GMP (guanosine 5'-monophosphate), with the release of PPi. Thus, specifically recycles hypoxanthine and guanine imported from the external medium, and converts them to IMP and GMP, respectively. Cannot use xanthine as substrate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | hpt |
| eggNOG description | Belongs to the purine pyrimidine phosphoribosyltransferase family |
| Orthologous group | COG0634 |
| EC number |
EC 2.4.2.8
|
| KEGG orthology |
K00760
|
| KEGG pathways |
map00230, map00983, map01100, map01110
|
| Gene Ontology (79) |
GO:0003674, GO:0003824, GO:0004422, GO:0006139, GO:0006163, GO:0006164, GO:0006177, GO:0006188, GO:0006725, GO:0006753, GO:0006793, GO:0006796 +67 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 | 0.888 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 |
|---|---|---|---|---|
Pribosyltran | PF00156.34 | 2.7e-21 | 48–197 | Phosphoribosyl transferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mesJ (tRNA(Ile)-lysidine synthase), high confidence from genomic context alone (score 987 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3625c mesJ |
tRNA(Ile)-lysidine synthase | 998 | 987 ctx | neighborhood:881 fusion:855 textmining:888 |
Rv3396c guaA |
GMP synthase | 973 | 940 | database:900 textmining:587 |
Rv3307 deoD |
purine nucleoside phosphorylase | 975 | 925 | database:900 textmining:693 |
Rv1021 mazG |
nucleoside triphosphate pyrophosphohydrolase | 923 | 923 | database:900 |
Rv0357c purA |
adenylosuccinate synthetase | 990 | 921 | database:900 textmining:882 |
Rv2584c apt |
adenine phosphoribosyltransferase | 993 | 917 | database:900 textmining:922 |
Rv0733 adk |
adenylate kinase | 940 | 916 ctx | fusion:887 |
Rv1389 gmk |
guanylate kinase | 963 | 915 | database:900 textmining:593 |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 932 | 912 | database:900 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 990 | 910 | database:900 textmining:893 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 911 | 905 | database:900 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 934 | 904 | database:900 |
Rv3410c guaB3 |
oxidoreductase | 920 | 904 | database:900 |
Rv3393 iunH |
nucleoside hydrolase | 967 | 901 | database:900 textmining:688 |
Rv3626c hyp |
hypothetical protein | 982 | 882 ctx | neighborhood:881 textmining:860 |
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: hypoxanthine-guanine phosphoribosyltransferase
- MTBC0 PGAP product: hypoxanthine phosphoribosyltransferase
- Pfam (hmmscan --cut_ga): Pribosyltran PF00156.34 (E=3e-21)
- (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_218141.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pribosyltran (PF00156.34)
- 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
COG0634 - Curated reference: UniProt P9WHQ9 (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 —
38 functional partner(s); context anchor
mesJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003841|Rv3624c|hpt MTPALVVGPAAWHAVHVTQSSSAITPGQTAELYPGDIKSVLLTAEQIQARIAELGEQIGNDYRELSATTGQDLLLITVLKGAVLFVTDLARAIPVPTQFEFMAVSSYGSSTSSSGVVRILKDLDRDIHGRDVLIVEDVVDSGLTLSWLSRNLTSRNPRSLRVCTLLRKPDAVHANVEIAYVGFDIPNDFVVGYGLDYDERYRDLSYIGTLDPRVYQ