Rv3656c Still unknown · low auto-curated
H37Rv Rv3656c · MTBC0 mtbc0_003874 ·
68 aa · 4119154–4119360 (-) ·
RefSeq NP_218173.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF4244 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF4244. Function unknown. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69624
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | DUF4244 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF4244) |
| Orthologous group | 2EHCF |
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 | 0.724 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
DUF4244 | PF14029.12 | 3.6e-23 | 13–65 | Protein of unknown function (DUF4244) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3657c (membrane protein), high confidence from genomic context alone (score 874 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) |
|---|---|---|---|---|
Rv3655c hyp |
hypothetical protein | 900 | 900 ctx | neighborhood:851 |
Rv3657c |
membrane protein | 983 | 874 ctx | neighborhood:835 textmining:870 |
Rv3659c |
conjugal transfer protein | 982 | 859 ctx | neighborhood:851 textmining:881 |
Rv3658c |
transmembrane protein | 857 | 857 ctx | neighborhood:851 |
Rv3654c hyp |
hypothetical protein | 968 | 853 ctx | neighborhood:851 textmining:796 |
Rv3660c ssd hyp |
hypothetical protein | 950 | 758 ctx | neighborhood:754 textmining:803 |
Rv0948c |
chorismate mutase | 709 | 710 ctx | cooccurence:708 |
Rv3605c hyp |
hypothetical protein | 653 | 653 ctx | cooccurence:653 |
Rv3793 embC |
arabinosyltransferase C | 634 | 635 ctx | cooccurence:633 |
Rv2179c |
3'-5' exoribonuclease | 625 | 625 ctx | cooccurence:625 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 625 | 625 ctx | cooccurence:624 |
Rv3795 embB |
arabinosyltransferase B | 620 | 620 ctx | cooccurence:620 |
Rv3794 embA |
arabinosyltransferase A | 606 | 606 ctx | cooccurence:606 |
Rv3231c hyp |
hypothetical protein | 525 | 525 ctx | cooccurence:522 |
Rv2927c sepIVA hyp |
hypothetical protein | 516 | 517 ctx | cooccurence:515 |
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: DUF4244 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF4244 PF14029.12 (E=4e-23)
- (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_218173.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4244 (PF14029.12)
- 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
2EHCF - Curated reference: UniProt O69624 (TrEMBL, unreviewed; Predicted)
- 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 64.9, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
24 functional partner(s); context anchor
Rv3657c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003874|Rv3656c| MLVITMFRVLVARMTALAVDESGMSTVEYAIGTIAAAAFGAILYTVVTGDSIVSALNRIIGRALSTKV