Rv3707c Resolved · high
H37Rv Rv3707c · MTBC0 - ·
336 aa · 4150030–4151040 (-) ·
RefSeq NP_218224.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | AraH2: endo-D-arabinofuranase, founding member (with AraH1/Rv1754c) of glycoside hydrolase family GH183 (Pfam DUF4185). Cleaves the D-arabinan core of arabinogalactan / lipoarabinomannan, i.e. mycobacterial cell-wall remodelling/degradation. NOTE: RefSeq/PGAP still annotate this gene as a hypothetical protein; it was characterised experimentally by Behrens et al. 2023. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
I6Y4C4
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF4185 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4185) |
| Orthologous group | COG0739 |
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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF4185 | PF13810.13 | 1.1e-50 | 11–325 | Domain of unknown function (DUF4185) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 93.2 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
8an0-assembly1_A |
1.00 | 0.90 | 2.4e-42 sig | 8an0-assembly1_A Endo-D-arabinofuranase AraH2 from Mycobacterium tuberculosis |
8ic1-assembly1_A |
1.00 | 0.76 | 1.1e-15 sig | 8ic1-assembly1_A endo-alpha-D-arabinanase EndoMA1 D51N mutant from Microbacterium arabinogalactanolyticum in complex with arabinooligosaccharides |
8hhv-assembly1_A |
1.00 | 0.74 | 1.6e-15 sig | 8hhv-assembly1_A endo-alpha-D-arabinanase EndoMA1 from Microbacterium arabinogalactanolyticum |
6xn0-assembly2_B |
1.00 | 0.53 | 6.4e-07 sig | 6xn0-assembly2_B Crystal structure of GH43_1 enzyme from Xanthomonas citri |
1w2t-assembly2_B |
1.00 | 0.52 | 5.8e-07 sig | 1w2t-assembly2_B beta-fructosidase from Thermotoga maritima in complex with raffinose |
3qef-assembly1_A |
1.00 | 0.60 | 6.1e-06 sig | 3qef-assembly1_A The structure and function of an arabinan-specific alpha-1,2-arabinofuranosidase identified from screening the activities of bacterial GH43 glycoside hydrolases |
6xn1-assembly2_B |
1.00 | 0.52 | 3.8e-06 sig | 6xn1-assembly2_B Crystal structure of the GH43_1 enzyme from Xanthomonas citri complexed with xylose |
1uyp-assembly4_D |
1.00 | 0.52 | 2.8e-06 sig | 1uyp-assembly4_D The three-dimensional structure of beta-fructosidase (invertase) from Thermotoga maritima |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pirG (cell surface protein), high confidence from genomic context alone (score 770 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) |
|---|---|---|---|---|
Rv3810 pirG |
cell surface protein | 770 | 770 ctx | cooccurence:769 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 762 | 762 ctx | cooccurence:761 |
Rv3709c ask |
aspartokinase | 757 | 758 ctx | neighborhood:755 |
Rv3708c asd |
aspartate-semialdehyde dehydrogenase | 757 | 757 ctx | neighborhood:755 |
Rv3593 lpqF |
lipoprotein LpqF | 753 | 754 ctx | cooccurence:750 |
Rv2743c hyp |
hypothetical protein | 753 | 753 ctx | cooccurence:752 |
Rv0817c lmeA hyp |
hypothetical protein | 748 | 749 ctx | cooccurence:747 |
Rv0518 hyp |
hypothetical protein | 717 | 718 ctx | cooccurence:716 |
Rv0479c |
membrane protein | 701 | 702 ctx | cooccurence:700 |
Rv0383c ttfA hyp |
hypothetical protein | 700 | 700 ctx | cooccurence:700 |
Rv3906c hyp |
hypothetical protein | 690 | 691 ctx | cooccurence:689 |
Rv1275 lprC |
lipoprotein LprC | 680 | 680 ctx | cooccurence:679 |
Rv0315 |
beta-1,3-glucanase | 673 | 673 ctx | cooccurence:672 |
Rv3710 leuA |
2-isopropylmalate synthase | 672 | 672 ctx | neighborhood:670 |
Rv1780 hyp |
hypothetical protein | 670 | 670 ctx | cooccurence:670 |
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
- MTBC0 PGAP product: hypothetical protein (not yet updated by RefSeq)
- Pfam: DUF4185 = glycoside hydrolase family GH183
- Foldseek: endo-D-arabinofuranase AraH2 (PDB 8AN0, E=2e-42, TM=0.90) -- the strongest structural hit in the genome
- Experimentally characterised as AraH2 by Behrens et al. 2023
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_218224.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4185 (PF13810.13)
- 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
COG0739 - Curated reference: UniProt I6Y4C4 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 93.2, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
96 functional partner(s); context anchor
pirG - Primary literature: Behrens MA, Lahiri S, et al. (2023). Identification of D-arabinan-degrading enzymes in mycobacteria Nature Communications. doi:10.1038/s41467-023-37839-5 PMID:37076525
Ancestral MTBC0 protein sequence
>H37Rv|Rv3707c| MLRIGPTAGTGTPTGDYGIGATDLCEFVEFPSQLLQVCGDSFAGQGVGFGGWYAPVALHVDTESIDDPAGVRYTGVTGVGTPLLADPTPPGDSQLPAGVVQINRRNYLMVTTTKDLQPQNSRLVRAEAARGGWQTVSGSRRNAAYQDGRQTQISGYYDPVPTPDSPTGWVYIVADSFTRGEPAVLYRATPESFTDRSRWQGWAGGPDGGWNKPPTPLWPDQLGEMSIRQIDGQTVLSYFNASTGNMEVRVAHHPTSLGAAPVTTVVRHDEWPEPAESLPPPYDNRLAQPYGGYISPGSTIDELRIFVSQWDTRARQNGPYRVIQFAVNPFKPWSDP