hemL Resolved · high auto-curated

H37Rv Rv0524 · MTBC0 mtbc0_000552 · 462 aa · 618292–619680 (+) · RefSeq NP_215038.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glutamate-1-semialdehyde 2,1-aminomutase
MTBC0 PGAP re-annotationglutamate-1-semialdehyde 2%2C1-aminomutase
Revised (this work)Glutamate-1-semialdehyde 2%2C1-aminomutase. Pfam: Aminotran_3 (PF00202.28).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WMN9 SwissProt · reviewed · Evidence at protein level
UniProt nameGlutamate-1-semialdehyde 2,1-aminomutase
EC (curated) EC 5.4.3.8

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namehemL
eggNOG descriptionAminotransferase
Orthologous groupCOG0001
EC number EC 5.4.3.8
KEGG orthology K01845
KEGG pathways map00860, map01100, map01110, map01120
KEGG modules M00121
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.16 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 16 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
Aminotran_3PF00202.28 1.5e-8746–449 Aminotransferase class-III

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: hemB (delta-aminolevulinic acid dehydratase), high confidence from genomic context alone (score 992 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0512 hemB delta-aminolevulinic acid dehydratase 997 992 ctx cooccurence:772 coexpression:622 database:900 textmining:689
Rv0509 hemA glutamyl-tRNA reductase 996 988 ctx cooccurence:771 database:900 textmining:706
Rv0525 hyp hypothetical protein 980 980 ctx neighborhood:882 coexpression:838
Rv0526 thioredoxin 991 974 ctx neighborhood:865 coexpression:816 textmining:675
Rv0527 ccdA cytochrome C-type biogenesis protein CcdA 970 915 ctx neighborhood:865 textmining:661
Rv0510 hemC porphobilinogen deaminase 955 915 ctx cooccurence:769 coexpression:564 textmining:502
Rv0529 ccsA cytochrome C-type biogenesis protein CcsA 935 909 ctx neighborhood:820 coexpression:412
Rv0528 transmembrane protein 872 855 ctx neighborhood:820
Rv2383c mbtB phenyloxazoline synthase 866 784 ctx neighborhood:544 experimental:417 textmining:408
Rv3266c rmlD dTDP-4-dehydrorhamnose reductase 745 746 coexpression:733
Rv3709c ask aspartokinase 733 718 coexpression:717
Rv0511 hemD uroporphyrin-III C-methyltransferase 821 706 ctx cooccurence:560 textmining:418
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 824 671 ctx cooccurence:556 textmining:489
Rv2947c pks15 polyketide synthase 669 654 ctx fusion:643
Rv2678c hemE uroporphyrinogen decarboxylase 886 624 ctx cooccurence:421 textmining:709

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: glutamate-1-semialdehyde 2,1-aminomutase
  • MTBC0 PGAP product: glutamate-1-semialdehyde 2%2C1-aminomutase
  • Pfam (hmmscan --cut_ga): Aminotran_3 PF00202.28 (E=2e-87)
  • (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_215038.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Aminotran_3 (PF00202.28)
  • 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 COG0001
  • Curated reference: UniProt P9WMN9 (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 — 64 functional partner(s); context anchor hemB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000552|Rv0524|hemL
MGSTEQATSRVRGAARTSAQLFEAACSVIPGGVNSPVRAFTAVGGTPRFITEAHGCWLIDADGNRYVDLVCSWGPMILGHAHPAVVEAVAKAAARGLSFGAPTPAETQLAGEIIGRVAPVERIRLVNSGTEATMSAVRLARGFTGRAKIVKFSGCYHGHVDALLADAGSGVATLGLCDDPQRPASPRSQSSRGLPSSPGVTGAAAADTIVLPYNDIDAVQQTFARFGEQIAAVITEASPGNMGVVPPGPGFNAALRAITAEHGALLILDEVMTGFRVSRSGWYGIDPVPADLFAFGKVMSGGMPAAAFGGRAEVMQRLAPLGPVYQAGTLSGNPVAVAAGLATLRAADDAVYTALDANADRLAGLLSEALTDAVVPHQISRAGNMLSVFFGETPVTDFASARASQTWRYPAFFHAMLDAGVYPPCSAFEAWFVSAALDDAAFGRIANALPAAARAAAQERPA