Rv3365c Resolved · high auto-curated
H37Rv Rv3365c · MTBC0 mtbc0_003580 ·
876 aa · 3801579–3804209 (-) ·
RefSeq NP_217882.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | sensor histidine kinase |
| Revised (this work) | Sensor histidine kinase. Pfam: DUF8316 (PF26990.1), HATPase_c (PF02518.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
Q93IG6
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | histidine kinase |
| EC (curated) |
EC 2.7.13.3
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
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 | 0.8 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 13 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 |
|---|---|---|---|---|
DUF8316 | PF26990.1 | 2.5e-07 | 75–332 | Domain of unknown function (DUF8316) |
HATPase_c | PF02518.32 | 2.6e-11 | 524–633 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3362c (ATP/GTP-binding protein), high confidence from genomic context alone (score 978 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3363c hyp |
hypothetical protein | 997 | 981 ctx | neighborhood:882 cooccurence:772 textmining:881 |
Rv3362c |
ATP/GTP-binding protein | 992 | 978 ctx | neighborhood:882 cooccurence:758 textmining:656 |
Rv3364c hyp |
hypothetical protein | 994 | 973 ctx | neighborhood:882 cooccurence:769 textmining:810 |
Rv3361c mfpA hyp |
hypothetical protein | 963 | 888 ctx | neighborhood:882 textmining:691 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 759 | 730 | experimental:422 database:538 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 742 | 727 | database:590 |
Rv1734c hyp |
hypothetical protein | 725 | 714 | experimental:401 database:538 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 723 | 712 | experimental:401 database:538 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 722 | 712 | experimental:401 database:538 |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 711 | 695 | database:586 |
Rv0977 PE_PGRS16 |
PE-PGRS family protein PE_PGRS16 | 705 | 695 ctx | cooccurence:694 |
Rv1157c hyp |
hypothetical protein | 678 | 662 ctx | cooccurence:660 |
Rv2542 hyp |
hypothetical protein | 638 | 638 ctx | cooccurence:636 |
Rv3877 eccD1 |
ESX-1 secretion system protein EccD1 | 633 | 634 ctx | cooccurence:632 |
Rv3143 |
response regulator | 639 | 626 |
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: hypothetical protein
- MTBC0 PGAP product: sensor histidine kinase
- Pfam (hmmscan --cut_ga): DUF8316 PF26990.1 (E=2e-07), HATPase_c PF02518.32 (E=3e-11)
- (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_217882.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF8316 (PF26990.1), HATPase_c (PF02518.32)
- 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
COG0642 - Curated reference: UniProt Q93IG6 (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 —
113 functional partner(s); context anchor
Rv3362c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003580|Rv3365c| MTMFARPTIPVAAAASDISAPAQPARGKPQQRPPSWSPRNWPVRWKVFTIALLPLVVAMVLAGLRVEAAMASTSGLRLVAARAEMIPAITKYMSALDVAVLASSTGHDVEGAQKNFTARKYELQTRLADTDVIADVRSGVNTLLNGGQALLDKVLADSIGLRDRVTAYAPLLLTAQNVIDASVRVDSEQIRTQVQGLSRAVGARGQMTMQEILVTRGADLAEPQLRSAMVTLAGTEPSTLFGMSAALGAGSPDTKNLQQQMVTRMAIMSDPAVALVNNPELLHSIQITRDIAEQVITDTTEAVTKSVQSQATDRRDAAIRDAVLVLAAIATAIVVVLVVARTLVGPMRVLRDGALKVAHTDLDGEIAAVRAGDEPIPEPLAVYTTEEIGQVAHAVDELHTRALLLAGEETRLRLLVNEMFETMSRRSRSLVDQQLSVIDQLERNEEDPARLDSLFRLDHLAARLRRNSANLLVLAGAQITRDHREPVPLSTVISAAVSEVEDYRRVDIARVPDCAVVGAAAGGVIHLLAELIDNALRYSSPTTPVRVAAAIGSEGSVLLRISDSGLGMTDADRRMANMRLRAGGEVTPDSARHMGLFVVGRLAGRHGIRVGLRGPVTGEQGTGTTAEVYLPLAVLEGTAPAQPPKPRVFAIKPPCPEPAAADPTDVPAAIGPLPPVTLLPRRTPGSSGIADVPAQPMQQRRRELKTPWWEDRFQQEPKQPPAPEPRPAPPPAKPAPPAGPVDDDVIYRRMLSEMVGDPHELAHSPDLDWKSVWDHGWSAAAEAADKPVQSRTDYGLPVREPGARLVPGAAVPEGPDREHPGAALASNGGLHPGRAPRHAAAVRDPDAVRASISSHFGGVRTGRSHARESSQGPNQQ