cycA Resolved · high auto-curated
H37Rv Rv1704c · MTBC0 mtbc0_001813 ·
556 aa · 1941801–1943471 (-) ·
RefSeq NP_216220.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-serine/alanine/glycine transporter protein CycA |
|---|---|
| MTBC0 PGAP re-annotation | amino acid permease |
| Revised (this work) | Amino acid permease. Pfam: AA_permease (PF00324.28), AA_permease_2 (PF13520.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33203
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | Probable D-serine/alanine/glycine transporter protein CycA |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | cycA |
| eggNOG description | permease |
| Orthologous group | COG1113 |
| KEGG orthology |
K03293, K11737, K16234
|
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 | 1.061 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 9 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 |
|---|---|---|---|---|
AA_permease | PF00324.28 | 5.7e-106 | 25–438 | Amino acid permease |
AA_permease_2 | PF13520.13 | 1.4e-38 | 29–451 | Amino acid permease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE22 (PPE family protein PPE22), high confidence from genomic context alone (score 716 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1705c PPE22 |
PPE family protein PPE22 | 716 | 716 ctx | neighborhood:714 |
Rv1703c |
methyltransferase | 673 | 673 ctx | neighborhood:664 |
Rv1706c PPE23 |
PPE family protein PPE23 | 566 | 566 ctx | neighborhood:564 |
Rv1979c |
permease | 430 | 259 | |
Rv3331 sugI |
sugar-transport integral membrane protein SugI | 449 | 232 | |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 535 | 90 | textmining:511 |
Rv3423c alr |
alanine racemase | 781 | 81 | textmining:772 |
Rv0407 fgd1 |
F420-dependent glucose-6-phosphate dehydrogenase | 587 | 73 | textmining:573 |
Rv3859c gltB |
glutamate synthase large subunit | 410 | 67 | |
Rv0701 rplC |
50S ribosomal protein L3 | 551 | 64 | textmining:540 |
Rv3261 fbiA |
2-phospho-L-lactate transferase | 421 | 64 | textmining:407 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 512 | 55 | textmining:506 |
Rv1305 atpE |
ATP synthase subunit C | 417 | 53 | textmining:410 |
Rv2447c folC |
folylpolyglutamate synthase FolC | 416 | 53 | textmining:409 |
Rv0006 gyrA |
DNA gyrase subunit A | 469 | 51 | textmining:464 |
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: D-serine/alanine/glycine transporter protein CycA
- MTBC0 PGAP product: amino acid permease
- Pfam (hmmscan --cut_ga): AA_permease PF00324.28 (E=6e-106), AA_permease_2 PF13520.13 (E=1e-38)
- (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_216220.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_permease (PF00324.28), AA_permease_2 (PF13520.13)
- 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
COG1113 - Curated reference: UniProt O33203 (TrEMBL, unreviewed; Inferred from homology)
- 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 —
26 functional partner(s); context anchor
PPE22 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001813|Rv1704c|cycA MPDDIAAADPTDTQPHLRRDLANRHIQLIAIGGAIGTGLFMGSGRTISLAGPAVMVVYGIIGFFVFFVLRAMGELLLSNLNYKSFVDFAADLLGPAAGFFVGWSYWFAWVVTGIADLVAITGYARFWWPGLPIWVPALVTVALILAVNLFSVRHFGELEFWFALIKVAAIVCLIAVGAILVATNFVSPHGVHATIENLWNDNGFFPTGFLGVVSGFQIAFFAYIGVELVGTAAAETADPRRTLPRAINAVPLRVAVFYIGALLAILAVVPWRQFASGESPFVTMFSLAGLAAAASVVNFVVVTAAASSANSGFFSTGRMLFGLADEGHAPAAFHQLNRGGVPAPALLLTAPLLLTSIPLLYAGRSVIGAFTLVTTVSSLLFMFVWAMIIISYLVYRRRHPQRHTDSVYKMPGGVVMCWAVLVFFAFVIWTLTTETETATALAWFPLWFVLLAVGWLVTQRRQSRRSFGFHCQVVGVRQQLGRGMARLAMKIHARPKLRSAVVVEPVSAGEPGARRSAKSVRKLASDDSQSAHCPVAVVGLADGGRDPQYHHDGPDR