Rv3605c Family assigned · low
H37Rv Rv3605c · MTBC0 mtbc0_003823 ·
158 aa · 4071409–4071885 (-) ·
RefSeq NP_218122.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3180 domain-containing protein |
| Revised (this work) | Polytopic integral membrane protein with 4 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
Curated reference (UniProt)
| UniProt |
O06277
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Probable conserved secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF3180) |
| Orthologous group | 2DRQG |
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 | 0.061 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 1 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 |
|---|---|---|---|---|
DUF3180 | PF11377.14 | 3.7e-38 | 9–146 | Protein of unknown function (DUF3180) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 90.6 (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 |
|---|---|---|---|---|
8fih-assembly1_C |
0.30 | 0.46 | 2.3e+00 | 8fih-assembly1_C Multi-state design of two-state switchable hinge proteins |
8ii8-assembly1_A |
0.30 | 0.36 | 1.0e+00 | 8ii8-assembly1_A X-ray crystal structure of pink-colored protein from Pleurotus salmoneostramineus in complex with natural chromophore |
8tsh-assembly1_L |
0.28 | 0.80 | 9.2e+00 | 8tsh-assembly1_L S. thermodepolymerans KpsMT(E151Q)-KpsE in complex with ATP |
8zah-assembly2_B |
0.21 | 0.47 | 4.0e+00 | 8zah-assembly2_B Crystal structure of the channel protein CorA from Campylobacter jejuni |
5voz-assembly1_S |
0.18 | 0.37 | 3.1e+00 | 5voz-assembly1_S Yeast V-ATPase in complex with Legionella pneumophila effector SidK (rotational state 3) |
8zak-assembly2_B |
0.18 | 0.47 | 5.1e+00 | 8zak-assembly2_B Crystal structure of the channel protein CorA from Campylobacter jejuni in complex with Ni2+ |
8zak-assembly1_A |
0.16 | 0.50 | 6.2e+00 | 8zak-assembly1_A Crystal structure of the channel protein CorA from Campylobacter jejuni in complex with Ni2+ |
8rtd-assembly1_H |
0.10 | 0.34 | 4.6e+00 | 8rtd-assembly1_H Stalk-Arches-IMC structure from the fully-assembled R388 type IV secretion system determined by cryo-EM. |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: folE (GTP cyclohydrolase I), high confidence from genomic context alone (score 887 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) |
|---|---|---|---|---|
Rv3609c folE |
GTP cyclohydrolase I | 887 | 887 ctx | neighborhood:881 |
Rv3606c folK |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase | 882 | 882 ctx | neighborhood:882 |
Rv3608c folP1 |
dihydropteroate synthase | 882 | 882 ctx | neighborhood:882 |
Rv3607c folB |
dihydroneopterin aldolase | 882 | 882 ctx | neighborhood:882 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 812 | 812 ctx | neighborhood:812 |
Rv3604c |
transmembrane protein | 780 | 780 ctx | neighborhood:734 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 767 | 767 ctx | cooccurence:767 |
Rv2179c |
3'-5' exoribonuclease | 746 | 746 ctx | cooccurence:746 |
Rv2468c hyp |
hypothetical protein | 741 | 741 ctx | cooccurence:741 |
Rv0948c |
chorismate mutase | 730 | 730 ctx | cooccurence:730 |
Rv3412 hyp |
hypothetical protein | 728 | 728 ctx | cooccurence:728 |
Rv2170 |
GCN5-like N-acetyltransferase | 722 | 722 ctx | cooccurence:722 |
Rv1638A hyp |
hypothetical protein | 714 | 714 ctx | cooccurence:714 |
Rv3311 hyp |
hypothetical protein | 699 | 699 ctx | cooccurence:699 |
Rv3004 cfp6 |
low molecular weight protein antigen 6 | 696 | 696 ctx | cooccurence:696 |
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
- DeepTMHMM: 4 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.
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_218122.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3180 (PF11377.14)
- 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
2DRQG - Curated reference: UniProt O06277 (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 90.6, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
89 functional partner(s); context anchor
folE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003823|Rv3605c| MGPTRKRDLTAAVVGAAAVGYLLVAVLYRWFPPITVWTGLSLLAVAVAEALWARYVRVKISDGEIGDGPGWLHPLVVARSLMVAKASAWVGALVTGWWIGVLAYFLPRRSWLRAAAEDTTGTVVAAGSALALVVAALWLQHCCKSPQDPTEHADGAES