Rv1754c Resolved · high
H37Rv Rv1754c · MTBC0 mtbc0_001867 ·
563 aa · 1997815–1999506 (-) ·
RefSeq NP_216270.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4185 domain-containing protein |
| Revised (this work) | AraH1: endo-D-arabinanase of glycoside hydrolase family GH183 (Pfam DUF4185). With AraH2 (Rv3707c), cleaves the D-arabinan of arabinogalactan/lipoarabinomannan, with a distinct substrate preference; involved in mycobacterial cell-wall modification/degradation. |
Curated reference (UniProt)
| UniProt |
O06790
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| eggNOG description | Domain of unknown function (DUF4185) |
| Orthologous group | COG4409 |
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 | 1.156 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 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 | 4.1e-119 | 234–559 | Domain of unknown function (DUF4185) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 83.6 (confident). 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 |
|---|---|---|---|---|
8ic1-assembly1_A |
1.00 | 0.84 | 3.9e-36 sig | 8ic1-assembly1_A endo-alpha-D-arabinanase EndoMA1 D51N mutant from Microbacterium arabinogalactanolyticum in complex with arabinooligosaccharides |
8hhv-assembly1_A |
1.00 | 0.84 | 4.9e-36 sig | 8hhv-assembly1_A endo-alpha-D-arabinanase EndoMA1 from Microbacterium arabinogalactanolyticum |
8glv-assembly1_Gs |
0.01 | 0.09 | 4.7e+00 | 8glv-assembly1_Gs 96-nm repeat unit of doublet microtubules from Chlamydomonas reinhardtii flagella |
6u42-assembly1_5F |
0.01 | 0.08 | 4.2e+00 | 6u42-assembly1_5F Natively decorated ciliary doublet microtubule |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3668c (protease), high confidence from genomic context alone (score 754 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) |
|---|---|---|---|---|
Rv3668c |
protease | 769 | 754 ctx | cooccurence:601 |
Rv0888 spmT hyp |
hypothetical protein | 764 | 733 | coexpression:732 |
Rv0312 hyp |
hypothetical protein | 714 | 696 | coexpression:625 |
Rv0431 |
tuberculin-like peptide | 679 | 679 ctx | cooccurence:676 |
Rv0053 rpsF |
30S ribosomal protein S6 | 631 | 632 | experimental:405 |
Rv3707c hyp |
hypothetical protein | 579 | 579 ctx | cooccurence:573 |
Rv1288 hyp |
hypothetical protein | 568 | 541 | |
Rv3499c mce4A |
Mce family protein Mce4A | 537 | 537 ctx | cooccurence:455 |
Rv0979A rpmF |
50S ribosomal protein L32 | 534 | 534 | experimental:405 |
Rv3443c rplM |
50S ribosomal protein L13 | 533 | 534 | experimental:405 |
Rv0682 rpsL |
30S ribosomal protein S12 | 556 | 532 | experimental:405 |
Rv2890c rpsB |
30S ribosomal protein S2 | 550 | 528 | experimental:405 |
Rv0720 rplR |
50S ribosomal protein L18 | 527 | 528 | experimental:405 |
Rv0714 rplN |
50S ribosomal protein L14 | 526 | 526 | experimental:405 |
Rv1642 rpmI |
50S ribosomal protein L35 | 529 | 511 | experimental:405 |
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: DUF4185 domain-containing protein
- Pfam: DUF4185 = glycoside hydrolase family GH183
- Foldseek: endo-alpha-D-arabinanase EndoMA1 (PDB 8IC1, E=4e-36, TM=0.84)
- Experimentally characterised as AraH1 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_216270.1)
- 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
COG4409 - Curated reference: UniProt O06790 (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 83.6, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
114 functional partner(s); context anchor
Rv3668c - 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
>mtbc0_001867|Rv1754c| MYRYQVRVQQRRSEMNRWVATRSRRHTYQWITDHKSPRDHYRHISELRTSIATSSPGRCDMSPIPRIVSVSLAWAAAIGLMVPIGLAPPAMAAPCSGDAANAPPPPSAIVTDPGATALGPVRPGHGPIPTGRKPRGANDRAPLPKLGPLISALLNPGARNAAPLQQQALVPRANPGPNPAPNPPATGPQPPNATQLTPNPAPAPDPAPAAAPDPGATLAGATTSLAEWVTGPDSPNKTLERFGISGTDLGIPWDNGDPANRQVLMIFGDTFGYCAVDGHQWRYNTLFRSQDRDLGNGVHVTSGDASNRYSGSPVRQPGFSKQLINSIKWARDETGIIPTAGIAVGKTQYVNFMSIRNWGRDGEWTTNYSGIAVSKDNGQTWGVFPGTIRASGPDSGGKARFVPGNENFQMGAYLKSNDGYLYSFGTPPGRGGSAYLARVPQRFVPDLTKYQYWNGDSNSWVPNKPDAATPVIPGPVGEMSVQYNTYLKQYLALYTNGMNDVVARTAPAPQGPWSAEQMLVSSWQMPGGIYAPMMHPWSTGKDVYFNLSLWSAYNVMLMHTVLP