alr Resolved · high auto-curated
H37Rv Rv3423c · MTBC0 - ·
408 aa · 3840194–3841420 (-) ·
RefSeq NP_217940.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | alanine racemase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Alanine racemase. Pfam: Ala_racemase_N (PF01168.27), Ala_racemase_C (PF00842.28). |
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 |
P9WQA9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Alanine racemase |
| EC (curated) |
EC 5.1.1.1
|
| Curated function | Catalyzes the interconversion of L-alanine and D-alanine. D-alanine plays a key role in peptidoglycan cross-linking. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | alr |
| eggNOG description | Catalyzes the interconversion of L-alanine and D- alanine. May also act on other amino acids |
| Orthologous group | COG0787 |
| EC number |
EC 5.1.1.1
|
| KEGG orthology |
K01775
|
| KEGG pathways |
map00473, map01100, map01502
|
| Gene Ontology (74) |
GO:0000270, GO:0003674, GO:0003824, GO:0005488, GO:0006022, GO:0006023, GO:0006024, GO:0006082, GO:0006520, GO:0006522, GO:0006523, GO:0006807 +62 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 | 0.258 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Ala_racemase_N | PF01168.27 | 1.0e-69 | 40–262 | Alanine racemase, N-terminal domain |
Ala_racemase_C | PF00842.28 | 3.0e-44 | 274–402 | Alanine racemase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tsaE (tRNA threonylcarbamoyladenosine biosynthesis protein), high confidence from genomic context alone (score 992 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3422c tsaE |
tRNA threonylcarbamoyladenosine biosynthesis protein | 996 | 992 ctx | neighborhood:882 fusion:695 coexpression:730 textmining:542 |
Rv2981c ddlA |
D-alanine--D-alanine ligase | 998 | 966 ctx | cooccurence:616 database:900 textmining:965 |
Rv2780 ald |
L-alanine dehydrogenase | 972 | 957 | coexpression:779 database:800 |
Rv2157c murF |
UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase | 987 | 935 ctx | fusion:835 cooccurence:590 textmining:816 |
Rv3421c tsaB hyp |
hypothetical protein | 955 | 906 ctx | neighborhood:881 textmining:548 |
Rv3419c gcp |
O-sialoglycoprotein endopeptidase | 916 | 887 ctx | neighborhood:881 |
Rv3420c rimI |
ribosomal-protein-alanine acetyltransferase RimI | 928 | 886 ctx | neighborhood:881 |
Rv0337c aspC |
aspartate aminotransferase | 865 | 807 | database:800 |
Rv1364c |
sigma factor regulatory protein | 739 | 740 ctx | neighborhood:544 coexpression:453 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 690 | 691 ctx | neighborhood:544 |
Rv1614 lgt |
prolipoprotein diacylglyceryl transferase | 682 | 671 | coexpression:600 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase | 687 | 657 | coexpression:646 |
Rv2155c murD |
UDP-N-acetylmuramoylalanine--D-glutamate ligase | 839 | 648 ctx | cooccurence:561 textmining:564 |
Rv2152c murC |
UDP-N-acetylmuramate--alanine ligase | 753 | 612 ctx | cooccurence:593 |
Rv1003 rsmI |
rRNA small subunit methyltransferase I | 564 | 564 ctx | cooccurence:432 |
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): alanine racemase
- Pfam (hmmscan --cut_ga): Ala_racemase_N PF01168.27 (E=1e-69), Ala_racemase_C PF00842.28 (E=3e-44)
- (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_217940.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ala_racemase_N (PF01168.27), Ala_racemase_C (PF00842.28)
- 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
COG0787 - Curated reference: UniProt P9WQA9 (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 —
88 functional partner(s); context anchor
tsaE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3423c|alr MKRFWENVGKPNDTTDGRGTTSLAMTPISQTPGLLAEAMVDLGAIEHNVRVLREHAGHAQLMAVVKADGYGHGATRVAQTALGAGAAELGVATVDEALALRADGITAPVLAWLHPPGIDFGPALLADVQVAVSSLRQLDELLHAVRRTGRTATVTVKVDTGLNRNGVGPAQFPAMLTALRQAMAEDAVRLRGLMSHMVYADKPDDSINDVQAQRFTAFLAQAREQGVRFEVAHLSNSSATMARPDLTFDLVRPGIAVYGLSPVPALGDMGLVPAMTVKCAVALVKSIRAGEGVSYGHTWIAPRDTNLALLPIGYADGVFRSLGGRLEVLINGRRCPGVGRICMDQFMVDLGPGPLDVAEGDEAILFGPGIRGEPTAQDWADLVGTIHYEVVTSPRGRITRTYREAENR