ppsB Resolved · high auto-curated

H37Rv Rv2932 · MTBC0 mtbc0_003115 · 1538 aa · 3272069–3276685 (+) · RefSeq NP_217448.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phthiocerol synthesis polyketide synthase type I PpsB
MTBC0 PGAP re-annotationphthiocerol type I polyketide synthase PpsB
Revised (this work)Phthiocerol type I polyketide synthase PpsB. Pfam: ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), SpnB_Rossmann (PF22953.4), KR (PF08659.17), adh_short (PF00106.32), PP-binding (PF00550.32).

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

Curated reference (UniProt)

UniProt P9WQE5 SwissProt · reviewed · Evidence at protein level
UniProt namePhenolphthiocerol/phthiocerol polyketide synthase subunit B
EC (curated) EC 2.3.1.292
Curated functionPart of the PpsABCDE complex involved in the biosynthesis of the lipid core common to phthiocerols and phenolphthiocerols by successive additions of malonyl-CoA or methylmalonyl-CoA extender units. PpsA can accept as substrate the activated forms of either icosanoyl (C20), docosanoyl (C22) or lignoceroyl (C24) groups from FadD26, or a (4-hydroxyphenyl)-C17 or (4-hydroxyphenyl)-C19 fatty acyl from FadD29. PpsA initiates the biosynthesis and extends its substrate using a malonyl-CoA extender unit. The PpsB and PpsC proteins add the second and third malonyl-CoA extender units. PpsD adds an (R)-me.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred nameppsB
eggNOG descriptionsynthase
Orthologous groupCOG1020
EC number EC 2.3.1.261
KEGG orthology K12430, K12440, K12441
Gene Ontology (66) GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006066, GO:0006082, GO:0006629, GO:0006631 +54 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 0.164 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 17 synonymous, 8 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
ketoacyl-syntPF00109.33 2.8e-10134–283 Beta-ketoacyl synthase, N-terminal domain
Ketoacyl-synt_CPF02801.29 2.9e-41291–405 Beta-ketoacyl synthase, C-terminal domain
KAsynt_C_assocPF16197.12 3.2e-11409–515 Ketoacyl-synthetase C-terminal extension
Acyl_transf_1PF00698.27 5.6e-115561–882 Acyl transferase domain
SpnB_RossmannPF22953.4 5.8e-12989–1136 Polyketide synthase extender module SpnB, Rossmann fold domain
KRPF08659.17 1.9e-481152–1327 KR domain
adh_shortPF00106.32 3.3e-121155–1308 short chain dehydrogenase
PP-bindingPF00550.32 2.0e-121431–1494 Phosphopantetheine attachment site

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

Closest characterised functional partner: fas (fatty acid synthase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2524c fas fatty acid synthase 999 1000 ctx neighborhood:544 coexpression:846 experimental:994 database:549 textmining:699
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 998 996 ctx neighborhood:892 experimental:458 database:900 textmining:545
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 997 996 ctx neighborhood:800 coexpression:802 database:900
Rv2930 fadD26 fatty-acid--CoA ligase FadD26 995 993 ctx neighborhood:801 coexpression:779 database:650
Rv2935 ppsE phthiocerol synthesis polyketide synthase type I PpsE 990 988 ctx neighborhood:798 database:900
Rv2934 ppsD phthiocerol synthesis polyketide synthase type I PpsD 987 986 ctx neighborhood:780 database:900
Rv2383c mbtB phenyloxazoline synthase 994 981 ctx neighborhood:544 coexpression:881 experimental:473 textmining:744
Rv0101 nrp peptide synthetase Nrp 985 972 ctx neighborhood:527 cooccurence:563 coexpression:768 experimental:473 textmining:501
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 976 969 coexpression:671 experimental:787 database:549
Rv2928 tesA thioesterase TesA 937 919 ctx cooccurence:719 database:500
Rv1181 pks4 polyketide beta-ketoacyl synthase 940 915 ctx neighborhood:481 database:720
Rv2380c mbtE peptide synthetase 926 902 ctx cooccurence:584 coexpression:452 experimental:473
Rv2948c fadD22 p-hydroxybenzoyl--AMP ligase 903 891 coexpression:770
Rv3800c pks13 polyketide synthase 941 890 ctx neighborhood:544 coexpression:660 textmining:484
Rv2950c fadD29 long-chain-fatty-acid--AMP ligase FadD29 903 876 database:650

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: phthiocerol synthesis polyketide synthase type I PpsB
  • MTBC0 PGAP product: phthiocerol type I polyketide synthase PpsB
  • Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=3e-101), Ketoacyl-synt_C PF02801.29 (E=3e-41), KAsynt_C_assoc PF16197.12 (E=3e-11), Acyl_transf_1 PF00698.27 (E=6e-115), SpnB_Rossmann PF22953.4 (E=6e-12), KR PF08659.17 (E=2e-48), adh_short PF00106.32 (E=3e-12), PP-binding PF00550.32 (E=2e-12)
  • (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_217448.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), SpnB_Rossmann (PF22953.4), KR (PF08659.17), adh_short (PF00106.32), PP-binding (PF00550.32)
  • 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 COG1020
  • Curated reference: UniProt P9WQE5 (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 — 314 functional partner(s); context anchor fas
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003115|Rv2932|ppsB
MMRTAFSRISGMTAQQRTSLADEFDRVSRIAVAEPVAVVGIGCRFPGDVDGPESFWDFLVAGRNAISTVPADRWDAEAFYHPDPLTPGRMTTKWGGFVPDVAGFDAEFFGITPREAAAMDPQQRMLLEVAWEALEHAGIPPDSLGGTRTAVMMGVYFNEYQSMLAASPQNVDAYSGTGNAHSITVGRISYLLGLRGPAVAVDTACSSSLVAVHLACQSLRLRETDLALAGGVSITLRPETQIAISAWGLLSPQGRCAAFDAAADGFVRGEGAGVVVLKRLTDAVRDGDQVLAVVRGSAVNQDGRSNGVTAPNTAAQCDVIADALRSGDVAPDSVNYVEAHGTGTVLGDPIEFEALAATYGHGGDACALGAVKTNIGHLEAAAGIAGFIKATLAVQRATIPPNLHFSQWNPAIDAASTRFFVPTQNSPWPTAEGPRRAAVSSFGLGGTNAHVIIEQGSELAPVSEGGEDTGVSTLVVTGKTAQRMAATAQVLADWMEGPGAEVAVADVAHTVNHHRARQATFGTVVARDRAQAIAGLRALAAGQHAPGVVSHQDGSPGPGTVFVYSGRGSQWAGMGRQLLADEPAFAAAVAELEPVFVEQAGFSLRDVIATGKELVGIEQIQLGLIGMQLTLTELWRSYGVQPDLVIGHSMGEVAAAVVAGALTPAEGLRVTATRARLMAPLSGQGGMALLGLDAAATEALIADYPQVTVGIYNSPRQTVIAGPTEQIDELIARVRAQNRFASRVNIEVAPHNPAMDALQPAMRSELADLTPRTPTIGIISTTYADLHTQPIFDAEHWATNMRNPVRFQQAIASAGSGADGAYHTFIEISAHPLLTQAIADTLEDAHRPTKSAAKYLSIGTLQRDADDTVTFRTNLYTADIAHPPHTCHPPEPHPTIPTTPWQHTHHWIATTHPSTAAPEDPGSNKVVVNGQSTSESRALEDWCHQLAWPIRPAVSADPPSTAAWLVVADNELCHELARAADSRVDSLSPPALAAGSDPAALLDALRGVDNVLYAPPVPGELLDIESAYQVFHATRRLAAAMVASSATAISPPKLFIMTRNAQPISEGDRANPGHAVLWGLGRSLALEHPEIWGGIIDLDDSMPAELAVRHVLTAAHGTDGEDQVVYRSGARHVPRLQRRTLPGKPVTLNADASQLVIGATGNIGPHLIRQLARMGAKTIVAMARKPGALDELTQCLAATGTDLIAVAADATDPAAMQTLFDRFGTELPPLEGIYLAAFAGRPALLSEMTDDDVTTMFRPKLDALALLHRLSLKSPVRHFVLFSSVSGLLGSRWLAHYTATSAFLDSFAGARRTMGLPATVVDWGLWKSLADVQKDATQISAESGLQPMADEVAIGALPLVMNPDAAVATVVVAADWPLLAAAYRTRGALRIVDDLLPAPEDVGKGESEFRTSLRSCPAEKRRDMLFDHVGALAATVMGMPPTEPLDPSAGFFQLGMDSLMSVTLQRALSESLGEFLPASVVFDYPTVYSLTDYLATVLPELLEIGATAVATQQATDSYHELTEAELLEQLSERLRGTQ