Rv3728 Resolved · high auto-curated
H37Rv Rv3728 · MTBC0 mtbc0_003953 ·
1065 aa · 4198994–4202191 (+) ·
RefSeq NP_218245.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | MFS transporter |
| Revised (this work) | MFS transporter. Pfam: Sugar_tr (PF00083.31), MFS_1 (PF07690.22), cNMP_binding (PF00027.36), Patatin (PF01734.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69695
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | Probable conserved two-domain membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismG Carbohydrate transport and metabolismP Inorganic ion transport and metabolismT Signal transduction mechanisms
|
|---|---|
| eggNOG description | Major facilitator superfamily |
| Orthologous group | COG0477 |
| KEGG orthology |
K07001
|
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) pseudogene candidate
| pN/pS | 0.616 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 18 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 2.89% of strains (4193) · clonal |
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 |
|---|---|---|---|---|
Sugar_tr | PF00083.31 | 5.6e-09 | 43–210 | Sugar (and other) transporter |
MFS_1 | PF07690.22 | 2.3e-39 | 47–275 | Major Facilitator Superfamily |
cNMP_binding | PF00027.36 | 9.5e-20 | 547–630 | Cyclic nucleotide-binding domain |
Patatin | PF01734.28 | 1.1e-29 | 806–964 | Patatin-like phospholipase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3727 (oxidoreductase), medium confidence from genomic context alone (score 647 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1714 |
oxidoreductase | 900 | 895 | coexpression:796 database:431 |
Rv1715 fadB3 |
3-hydroxybutyryl-CoA dehydrogenase FadB | 810 | 804 | coexpression:797 |
Rv1716 hyp |
hypothetical protein | 791 | 791 | coexpression:785 |
Rv1718 hyp |
hypothetical protein | 730 | 730 | coexpression:730 |
Rv1358 |
transcriptional regulator | 722 | 655 | experimental:440 |
Rv3727 |
oxidoreductase | 770 | 647 ctx | neighborhood:529 |
Rv2488c |
LuxR family transcriptional regulator | 714 | 645 | experimental:440 |
Rv2438c nadE |
glutamine-dependent NAD(+) synthetase | 660 | 629 ctx | neighborhood:544 |
Rv1527c pks5 |
polyketide synthase | 769 | 613 | database:431 textmining:429 |
Rv2048c pks12 |
polyketide synthase | 765 | 605 | database:431 textmining:429 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 785 | 598 | database:431 textmining:489 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 760 | 598 | database:431 textmining:429 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 759 | 596 | database:431 textmining:429 |
Rv0386 |
transcriptional regulator | 672 | 593 | experimental:440 |
Rv1990A |
Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g | 612 | 591 | database:431 |
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: membrane protein
- MTBC0 PGAP product: MFS transporter
- Pfam (hmmscan --cut_ga): Sugar_tr PF00083.31 (E=6e-09), MFS_1 PF07690.22 (E=2e-39), cNMP_binding PF00027.36 (E=1e-19), Patatin PF01734.28 (E=1e-29)
- (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_218245.1)
- Domains: Pfam-A via hmmscan --cut_ga — Sugar_tr (PF00083.31), MFS_1 (PF07690.22), cNMP_binding (PF00027.36), Patatin (PF01734.28)
- 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
COG0477 - Curated reference: UniProt O69695 (TrEMBL, unreviewed; Inferred from homology)
- 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 —
132 functional partner(s); context anchor
Rv3727 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003953|Rv3728| MHTVATNNAAPVIAAGPVGPSRRRRRVHAPLTRRRQPSSSAVLLVAAFGAFLAFLDSTIVNVAFPDIQRHFHSDISDLSWMLNAYNIVFAAFLVAAGRLADLMGRKRVFILGVALFTVASGLCAIAESVGELVAFRVLQGIGAAVLVPASLGLVVEAFPAERRAHGVNLWGAAGAIAAGLGPPIGGALIEADGWRWVFLVNLPLGVFAVLAARRALVENRAAGRRRVPDVRGAVLLAFALGLLTLGLIKGPDWGWASLPTSGSLLAAAVAMVGFVMSSRHHPAPMVEPTLLRIQSFVAGTGLTAVASAGFYAYLLTHVLFLNYVWGYTLLEAGMAVAPAALVAAVVAAVLGRVADRHGYRFIVGIGALIWAASLLWYLKVVGSQPDFLGEWLPGQILQGIGVGATFPLLGSAALARLAKGGSYATASAVTGTIRQVGAVIGVAVLVILVGTPAPGAAEEALRHGWALAAICFVAVGIGALSLGRIRPVPAAVEPPPGPPVAPLGARRPPRPAPVASPAAAVAPTPKTSREVNLLEALRFARPDTQQIELQAGSYLFHAGDVSDALYVVRSGRLQVLAGDGAKDEVVAELGRGQVVGELGVLLDAPRSASVRAVRDSSLMRVTKAEFAKIADAGVLGALAGVLAKRQHQTRVASQRTTPEVVVAVVGVDANAPVAMVATELCRALSTRLRAVAPGRVDCDGLERAEQTADRVVLHAAVGDARWREFCLRVADRVVLVASNPAVPVAPLPTRATGADLVLAGRPAGREHRRAWEQLITPRSMHVVRREFVADDLRVLATRIAGRSVGLVLSGGAARACAHLGVLEELEAAGVTVDRFAGTSMGAIIAALAASGLDAAGVDAQIYEHFVRKSHGDYTLPSKGLIRGKRTQSTLRTIFGDHLVEELPKHFRCVSVDLLARRPVVHRQGPLADVVGCSMRLPFLYAPLPYGGTLHVDGGVLDNVPVTTLVGKDGPLIAVNVASGGNPSPASGGHRRGKPRVPGLTDTLLRTMTISSAMASEKVLAQADLVIKPNPIGVGLMEYHQIDRAREAGRIAAREALPQIMELVHG