sap Resolved · high auto-curated

H37Rv Rv3821 · MTBC0 mtbc0_004050 · 237 aa · 4310083–4310796 (+) · RefSeq NP_218338.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane protein
MTBC0 PGAP re-annotationsulfolipid-1 biosynthesis transporter Sap
Revised (this work)Sulfolipid-1 biosynthesis transporter Sap. Pfam: SfLAP (PF11139.15).

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

Curated reference (UniProt)

UniProt O07802 SwissProt · reviewed · Evidence at protein level
UniProt nameSulfolipid-1 exporter Sap
Curated functionRequired for the transport across the inner membrane of sulfolipid-1 (SL-1), which is a major cell wall lipid of pathogenic mycobacteria. Could also transport SL1278 (2-palmitoyl-3-(C43)-phthioceranyl-alpha, alpha'-D-trehalose-2'-sulfate), which is the precursor of SL-1. May potentiate SL-1 levels and confer specificity for sulfolipids over structurally similar glycolipids.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionSap, sulfolipid-1-addressing protein
Orthologous group2F6DN

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 1.356 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 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
SfLAPPF11139.15 4.0e-575–235 Sap, sulfolipid-1-addressing protein

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

Closest characterised functional partner: papA2 (trehalose-2-sulfate acyltransferase), medium confidence from genomic context alone (score 549 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3822 chp1 hyp hypothetical protein 850 707 ctx neighborhood:703 textmining:511
Rv3820c papA2 trehalose-2-sulfate acyltransferase 681 549 ctx neighborhood:542
Rv1337 integral membrane protein 517 55 textmining:510
Rv0227c membrane protein 440 55 textmining:432
Rv0295c stf0 hyp hypothetical protein 549 53 textmining:544
Rv1275 lprC lipoprotein LprC 442 51 textmining:437
Rv2169c transmembrane protein 518 50 textmining:514
Rv1799 lppT lipoprotein LppT 440 50 textmining:435
Rv3823c mmpL8 integral membrane transport protein MmpL8 406 47 textmining:403
Rv0625c transmembrane protein 548 46 textmining:546
Rv3271c integral membrane protein 547 44 textmining:546
Rv3064c integral membrane protein 544 44 textmining:543
Rv0585c integral membrane protein 653 41 textmining:653

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: integral membrane protein
  • MTBC0 PGAP product: sulfolipid-1 biosynthesis transporter Sap
  • Pfam (hmmscan --cut_ga): SfLAP PF11139.15 (E=4e-57)
  • (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_218338.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SfLAP (PF11139.15)
  • 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 2F6DN
  • Curated reference: UniProt O07802 (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 — 13 functional partner(s); context anchor papA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004050|Rv3821|sap
MWSTVLVLALSVICEPVRIGLVVLMLNRRRPLLHLLTFLCGGYTMAGGVAMVTLVVLGATPLAGHFSVAEVQIGTGLIALLIAFALTTNVIGKHVRRATHARVGDDGGRVLRESVPPSGAHKLAVRARCFLQGDSLYVAGVSGLGAALPSANYMGAMAAILASGATPATQALAVVTFNVVAFTVAEVPLVSYLAAPRKTRAFMAALQSWLRSRSRRDAALLVAAGGCLMLTLGLSNL