Rv3603c Family assigned · medium auto-curated
H37Rv Rv3603c · MTBC0 mtbc0_003821 ·
303 aa · 4068911–4069822 (-) ·
RefSeq NP_218120.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | Rossmann-like and DUF2520 domain-containing protein |
| Revised (this work) | Rossmann-like and DUF2520 domain-containing protein. Pfam: Rossmann-like (PF10727.16), F420_oxidored (PF03807.24), DUF2520 (PF10728.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06279
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved hypothetical alanine and leucine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Domain of unknown function (DUF2520) |
| Orthologous group | COG5495 |
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 | 0.182 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 17 synonymous, 8 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 |
|---|---|---|---|---|
Rossmann-like | PF10727.16 | 3.5e-60 | 5–128 | Rossmann-like domain |
F420_oxidored | PF03807.24 | 7.8e-05 | 13–93 | NADP oxidoreductase coenzyme F420-dependent |
DUF2520 | PF10728.15 | 1.6e-33 | 145–286 | Domain of unknown function (DUF2520) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: panC (pantothenate synthetase), high confidence from genomic context alone (score 986 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) |
|---|---|---|---|---|
Rv3602c panC |
pantothenate synthetase | 997 | 986 ctx | neighborhood:881 fusion:795 cooccurence:471 textmining:806 |
Rv3601c panD |
aspartate 1-decarboxylase | 940 | 915 ctx | neighborhood:881 |
Rv3600c coaX |
type III pantothenate kinase | 986 | 897 ctx | neighborhood:881 textmining:870 |
Rv3598c lysS |
lysine--tRNA ligase | 957 | 791 ctx | neighborhood:773 textmining:803 |
Rv3604c |
transmembrane protein | 740 | 740 ctx | neighborhood:740 |
Rv3597c lsr2 |
iron-regulated H-NS-like protein | 702 | 702 ctx | neighborhood:702 |
Rv3607c folB |
dihydroneopterin aldolase | 661 | 661 ctx | neighborhood:661 |
Rv3609c folE |
GTP cyclohydrolase I | 661 | 661 ctx | neighborhood:661 |
Rv3608c folP1 |
dihydropteroate synthase | 661 | 661 ctx | neighborhood:661 |
Rv3605c hyp |
hypothetical protein | 661 | 661 ctx | neighborhood:661 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 657 | 657 ctx | neighborhood:657 |
Rv2225 panB |
3-methyl-2-oxobutanoate hydroxymethyltransferase | 783 | 547 ctx | cooccurence:484 textmining:541 |
Rv2146c |
transmembrane protein | 526 | 526 ctx | cooccurence:499 |
Rv3596c clpC1 |
ATP-dependent protease ATP-binding subunit ClpC | 443 | 443 ctx | neighborhood:443 |
Rv3606c folK |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase | 427 | 427 ctx | neighborhood:427 |
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: Rossmann-like and DUF2520 domain-containing protein
- Pfam (hmmscan --cut_ga): Rossmann-like PF10727.16 (E=3e-60), F420_oxidored PF03807.24 (E=8e-05), DUF2520 PF10728.15 (E=2e-33)
- (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_218120.1)
- Domains: Pfam-A via hmmscan --cut_ga — Rossmann-like (PF10727.16), F420_oxidored (PF03807.24), DUF2520 (PF10728.15)
- 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
COG5495 - Curated reference: UniProt O06279 (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)
- 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
panC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003821|Rv3603c| MERFDGLRPARLKVGIISAGRVGTALGVALQRADHVVVACSAISHASRRRAQRRLPDTPVLPPLDVAASAELLLLAVTDSELAGLVSGLAATSAVRPQTIVAHTSGANGIGILAPLAQQGCIPLAIHPAMTFTGSDEDISRLPDTCFGITAADDVGYAIGQSLVLEMGGEPFCVREDARILYHAALAHASNHIVTVLADALEALRAALSGGELLGQQTVDDQPGGIVERIVGPLARAALENTLQRGQAALTGPVARGDAAAVADHLAALADVDAALAQAYRINALRTAQRAHAPADVVEVLTA