hemN Resolved · high auto-curated
H37Rv Rv2388c · MTBC0 - ·
375 aa · 2682015–2683142 (-) ·
RefSeq NP_216904.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxygen-independent coproporphyrinogen III oxidase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Oxygen-independent coproporphyrinogen III oxidase. Pfam: Radical_SAM (PF04055.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WP73
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Heme chaperone HemW |
| Curated function | Probably acts as a heme chaperone, transferring heme to an unknown acceptor. Binds one molecule of heme per monomer, possibly covalently (By similarity). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemN |
| eggNOG description | Involved in the biosynthesis of porphyrin-containing compound |
| Orthologous group | COG0635 |
| Gene Ontology (37) |
GO:0003674, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006725, GO:0006778, GO:0006779, GO:0006807, GO:0008150, GO:0008152 +25 more
|
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 | 0.37 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.63% of strains (913) · clonal |
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 |
|---|---|---|---|---|
Radical_SAM | PF04055.28 | 1.3e-20 | 10–182 | Radical SAM superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rpfD (resuscitation-promoting factor RpfD), medium confidence from genomic context alone (score 642 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2389c rpfD |
resuscitation-promoting factor RpfD | 726 | 642 ctx | neighborhood:640 |
Rv2390c hyp |
hypothetical protein | 826 | 571 ctx | neighborhood:570 textmining:611 |
Rv2879c rlmN |
Conserved hypothetical protein; Specifically methylates position 2 of adenine 2503 in 23S rRNA and position 2 of adenine 37 in tRNAs; Belong | 605 | 564 ctx | cooccurence:546 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 661 | 558 | database:500 |
Rv3859c gltB |
glutamate synthase large subunit | 687 | 545 ctx | neighborhood:544 |
Rv2880c |
Rv2880c, (MTCY274.11c), len: 275 aa. Conserved hypothetical protein, highly similar in N-terminus to others e.g. O86754|SC6A9.22c hypothetic | 549 | 503 ctx | cooccurence:479 |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 503 | 503 ctx | cooccurence:458 |
Rv3232c ppk2 |
polyphosphate kinase | 501 | 502 | coexpression:473 |
Rv2391 sirA |
sulfite reductase | 503 | 496 ctx | neighborhood:488 |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 508 | 490 ctx | neighborhood:482 |
Rv0213c |
methyltransferase | 518 | 446 | coexpression:420 |
Rv2148c hyp |
hypothetical protein | 442 | 443 | |
Rv2733c miaB |
(dimethylallyl)adenosine tRNA methylthiotransferase | 509 | 438 | |
Rv0408 pta |
phosphate acetyltransferase | 600 | 434 | coexpression:416 |
Rv1292 argS |
arginine--tRNA ligase | 414 | 414 | coexpression:413 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): oxygen-independent coproporphyrinogen III oxidase
- Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=1e-20)
- (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_216904.1)
- Domains: Pfam-A via hmmscan --cut_ga — Radical_SAM (PF04055.28)
- 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
COG0635 - Curated reference: UniProt P9WP73 (SwissProt, reviewed; 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 —
35 functional partner(s); context anchor
rpfD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2388c|hemN MPGQPFGVYLHVPFCLTRCGYCDFNTYTPAQLGGVSPDRWLLALRAELELAAAKLDAPTVHTVYVGGGTPSLLGGERLATLLDMVRDHFVLAPDAEVSTEANPESTWPEFFATIRAAGYTRVSLGMQSVAPRVLATLDRVHSPGRAAAAATEAIAEGFTHVNLDLIYGTPGESDDDLVRSVDAAVQAGVDHVSAYALVVEHGTALARRVRRGELAAPDDDVLAHRYELVDARLSAAGFAWYEVSNWCRPGGECRHNLGYWDGGQWWGAGPGAHGYIGVTRWWNVKHPNTYAEILAGATLPVAGFEQLGADALHTEDVLLKVRLRQGLPLARLGAAERERAEAVLADGLLDYHGDRLVLTGRGRLLADAVVRTLLG