hemZ Resolved · high auto-curated
H37Rv Rv1485 · MTBC0 mtbc0_001588 ·
344 aa · 1684822–1685856 (+) ·
RefSeq NP_216001.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ferrochelatase |
|---|---|
| MTBC0 PGAP re-annotation | ferrochelatase |
| Revised (this work) | Ferrochelatase. Pfam: Ferrochelatase (PF00762.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNE3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Coproporphyrin III ferrochelatase |
| EC (curated) |
EC 4.99.1.9
|
| Curated function | Involved in coproporphyrin-dependent heme b biosynthesis. Catalyzes the insertion of ferrous iron into coproporphyrin III to form Fe-coproporphyrin III. Has weaker activity with coproporphyrin I, protoporphyrin IX, deuteroporphyrin, 2,4 hydroxyethyl and 2,4 disulfonate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | hemH |
| eggNOG description | Catalyzes the ferrous insertion into protoporphyrin IX |
| Orthologous group | COG0276 |
| EC number |
EC 4.99.1.1, EC 4.99.1.9
|
| KEGG orthology |
K01772
|
| KEGG pathways |
map00860, map01100, map01110
|
| KEGG modules |
M00121
|
| Gene Ontology (45) |
GO:0003674, GO:0003824, GO:0004325, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006725, GO:0006778, GO:0006779, GO:0006783, GO:0006807 +33 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 | 0.087 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
Ferrochelatase | PF00762.25 | 1.7e-83 | 4–296 | Ferrochelatase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hemY (protoporphyrinogen oxidase), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2677c hemY |
protoporphyrinogen oxidase | 997 | 993 ctx | cooccurence:749 coexpression:712 database:900 textmining:582 |
Rv2676c hemQ hyp |
hypothetical protein | 964 | 958 ctx | fusion:881 coexpression:458 |
Rv2678c hemE |
uroporphyrinogen decarboxylase | 989 | 952 ctx | cooccurence:764 coexpression:773 textmining:788 |
Rv0958 |
magnesium chelatase | 926 | 917 | database:900 |
Rv0846c mmcO |
oxidase | 925 | 914 | database:900 |
Rv2850c |
magnesium chelatase | 942 | 911 | database:900 |
Rv1451 ctaB |
protoheme IX farnesyltransferase | 927 | 906 | database:900 |
Rv3841 bfrB |
bacterioferritin BfrB | 913 | 901 | database:900 |
Rv1876 bfrA |
bacterioferritin BfrA | 936 | 900 | database:900 |
Rv1484 inhA |
NADH-dependent enoyl-[ACP | 904 | 888 ctx | neighborhood:882 |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 879 | 862 ctx | neighborhood:857 |
Rv0510 hemC |
porphobilinogen deaminase | 891 | 613 | coexpression:408 textmining:731 |
Rv1480 hyp |
hypothetical protein | 550 | 551 ctx | neighborhood:544 |
Rv1481 |
membrane protein | 591 | 550 ctx | neighborhood:544 |
Rv1479 moxR1 |
transcriptional regulator MoxR1 | 726 | 547 ctx | neighborhood:544 textmining:422 |
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: ferrochelatase
- MTBC0 PGAP product: ferrochelatase
- Pfam (hmmscan --cut_ga): Ferrochelatase PF00762.25 (E=2e-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_216001.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ferrochelatase (PF00762.25)
- 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
COG0276 - Curated reference: UniProt P9WNE3 (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 —
48 functional partner(s); context anchor
hemY - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001588|Rv1485|hemZ MQFDAVLLLSFGGPEGPEQVRPFLENVTRGRGVPAERLDAVAEHYLHFGGVSPINGINRTLIAELEAQQELPVYFGNRNWEPYVEDAVTAMRDNGVRRAAVFATSAWSGYSSCTQYVEDIARARRAAGRDAPELVKLRPYFDHPLFVEMFADAITAAAATVRGDARLVFTAHSIPTAADRRCGPNLYSRQVAYATRLVAAAAGYCDFDLAWQSRSGPPQVPWLEPDVTDQLTGLAGAGINAVIVCPIGFVADHIEVVWDLDHELRLQAEAAGIAYARASTPNADPRFARLARGLIDELRYGRIPARVSGPDPVPGCLSSINGQPCRPPHCVASVSPARPSAGSP