Rv3531c Family assigned · low auto-curated · to review
H37Rv Rv3531c · MTBC0 mtbc0_003748 ·
375 aa · 3991494–3992621 (-) ·
RefSeq NP_218048.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 3u07-assembly2_B Crystal Structure of the VPA0106 protein from Vibrio parahaemol (prob 1.00, TM 0.41). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
I6XHH2
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DUF1214 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Conserved Protein |
| Orthologous group | COG5361 |
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 | 0.327 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 10 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.1 (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 |
|---|---|---|---|---|
6ans-assembly2_D |
1.00 | 0.83 | 1.5e-32 sig | 6ans-assembly2_D Crystal structure of a putative uncharacterized protein from Burkholderia cenocepacia |
3u07-assembly2_B |
1.00 | 0.41 | 3.8e-11 sig | 3u07-assembly2_B Crystal Structure of the VPA0106 protein from Vibrio parahaemolyticus. Northeast Structural Genomics Consortium Target VpR106. |
3u07-assembly3_C |
1.00 | 0.43 | 3.0e-10 sig | 3u07-assembly3_C Crystal Structure of the VPA0106 protein from Vibrio parahaemolyticus. Northeast Structural Genomics Consortium Target VpR106. |
8jun-assembly1_B |
0.97 | 0.23 | 4.3e-06 sig | 8jun-assembly1_B Cryo-EM structure of SIDT1 E555Q mutant |
5w6h-assembly1_C |
0.77 | 0.46 | 3.5e-02 | 5w6h-assembly1_C Crystal structure of Bacteriophage CBA120 tailspike protein 4 enzymatically active domain (TSP4dN, orf213) |
3lkj-assembly1_B |
0.75 | 0.35 | 7.4e-03 sig | 3lkj-assembly1_B Small Molecule Inhibition of the TNF Family Cyokine CD40 Ligand Through a Subunit Fracture Mechanism |
1o6u-assembly3_E |
0.69 | 0.49 | 7.6e-02 | 1o6u-assembly3_E The Crystal Structure of Human Supernatant Protein Factor |
6qe7-assembly3_C |
0.63 | 0.19 | 8.4e-05 sig | 6qe7-assembly3_C anti-sigma factor domain-containing protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3530c (oxidoreductase), high confidence from genomic context alone (score 972 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) |
|---|---|---|---|---|
Rv3529c hyp |
hypothetical protein | 975 | 975 ctx | neighborhood:881 cooccurence:774 |
Rv3530c |
oxidoreductase | 996 | 972 ctx | neighborhood:882 cooccurence:646 textmining:870 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 817 | 817 ctx | cooccurence:766 |
Rv0310c hyp |
hypothetical protein | 785 | 786 ctx | cooccurence:746 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 769 | 769 ctx | cooccurence:735 |
Rv3542c chsH2 hyp |
hypothetical protein | 731 | 731 ctx | cooccurence:728 |
Rv3568c hsaC |
extradiol dioxygenase | 728 | 728 ctx | cooccurence:716 |
Rv3541c chsH1 hyp |
hypothetical protein | 707 | 707 ctx | cooccurence:704 |
Rv3521 hyp |
hypothetical protein | 704 | 704 ctx | cooccurence:703 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 700 | 700 ctx | cooccurence:664 |
Rv1817 |
flavoprotein | 666 | 666 ctx | cooccurence:665 |
Rv3552 |
CoA-transferase subunit beta | 653 | 653 ctx | cooccurence:651 |
Rv3551 |
CoA-transferase subunit alpha | 641 | 641 ctx | cooccurence:639 |
Rv3527 hyp |
hypothetical protein | 638 | 638 ctx | cooccurence:540 |
Rv0311 hyp |
hypothetical protein | 636 | 637 ctx | cooccurence:635 |
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: hypothetical protein
- Foldseek best: 6ans-assembly2_D Crystal structure of a putative uncharacterized protein from Bu (prob 1.00, E=1e-32, TM=0.83)
- (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_218048.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG5361 - Curated reference: UniProt I6XHH2 (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 95.1, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
42 functional partner(s); context anchor
Rv3530c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003748|Rv3531c| MYSDPLREAIAEAEQLVAAAPHIETEADLLEGLQYLAGCIAGCMHLAFDYERDHPFLQSGTGPFTKMGLDNPDTLYFGTRLQANRDYVVSGRRGTTTDLSFQLLGGEYTDYNVPASQAAFDDRELDIAADGSFEWRLRPSAPGQLVIREVYGDWSQQRGTLAIARLDTVGTAPPPLTRELMEKRYATAGSQLVNRVKTWLQFPQWFYLNIPVNTMVAPRLTPGGLATQYSSAGHFELRPGQALVITVPVSDAPYLGFQLGSMWYISLDYINHQTSLNASQAQADPDGKVRIVVAEQNPGVTNWVETLGHRRGFLQFRWQRVSRELTEADGPTVELVDFDAIPAALPHYQHNKISEDDWRARIALRQRQIATRMLG