UniProtKB - Q4WLW8 (FMQC_ASPFU)
Nonribosomal peptide synthetase fmqC
fmqC
Functioni
Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of the antitumor fumiquinazolines that confer a dual-usage capability to defend against phagocytes in the environment and animal hosts (PubMed:20225828, PubMed:20804163, PubMed:21899262, PubMed:24612080, PubMed:33705521).
The simplest member is fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic acid (Ant), tryptophan (Trp), and alanine (Ala) (PubMed:20225828).
The trimodular NRPS fmqA is responsible for FQF formation (PubMed:20225828).
Modules 1, 2 and 3 of fmqA are predicted to activate and load Ant, Trp and Ala, respectively, providing for the assembly of an Ant-Trp-Ala-S-enzyme intermediate that would undergo double cyclization for chain release and generation of the tricyclic 6-6-6 product fumiquinazoline F (PubMed:20225828).
The presence of an E domain predicted for module 2 of fmqA is consistent with epimerization of L-Trp to D-Trp during assembly to generate the R-stereocenter at C14 of FQF (PubMed:20225828).
The FAD-dependent monooxygenase fmqB and the monomodular NRPS fmqC then maturate FQF to FQA (PubMed:20804163).
FmqB oxidizes the 2',3'-double bond of the indole side chain of FQF, and fmqC activates L-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier protein domain, and acylates the oxidized indole for subsequent intramolecular cyclization to create the 6-5-5-imidazolindolone of FQA (PubMed:20804163).
The FAD-linked oxidoreductase fmqD introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring (PubMed:21899262).
FQC subsequently converts nonenzymatically to the known cyclic aminal FQD (PubMed:21899262).
5 Publications: Alkaloid biosynthesis Pathwayi
This protein is involved in Alkaloid biosynthesis.2 PublicationsView all proteins of this organism that are known to be involved in Alkaloid biosynthesis.
GO - Molecular functioni
- ligase activity Source: UniProtKB-KW
- phosphopantetheine binding Source: GO_Central
GO - Biological processi
- amino acid activation for nonribosomal peptide biosynthetic process Source: GO_Central
- bioluminescence Source: UniProtKB-KW
- fumigaclavine C biosynthetic process Source: AspGD
- fumiquinazoline A biosynthetic process Source: AspGD
- fumiquinazoline C biosynthetic process Source: AspGD
- nonribosomal peptide biosynthetic process Source: AspGD
- secondary metabolic process Source: AspGD
- secondary metabolite biosynthetic process Source: AspGD
Keywordsi
Molecular function | Ligase, Photoprotein |
Biological process | Luminescence, Virulence |
Names & Taxonomyi
Protein namesi | Recommended name: Nonribosomal peptide synthetase fmqC1 Publication (EC:6.3.2.-1 Publication)Alternative name(s): Fumiquinazoline biosynthesis cluster protein C1 Publication |
Gene namesi | Name:fmqC1 Publication Synonyms:NRPS111 Publication, pesL1 Publication ORF Names:AFUA_6G12050 |
Organismi | Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) (Aspergillus fumigatus) |
Taxonomic identifieri | 330879 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Aspergillaceae › Aspergillus › Aspergillus subgen. Fumigati › |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | FungiDB:Afu6g12050 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- cytoplasm Source: AspGD
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000416552 | 1 – 1160 | Nonribosomal peptide synthetase fmqCAdd BLAST | 1160 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 679 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphopantetheine, PhosphoproteinExpressioni
Inductioni
Interactioni
Subunit structurei
Interacts with the mitogen-activated protein kinase mpkA.
1 PublicationProtein-protein interaction databases
STRINGi | 746128.CADAFUBP00007607 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 642 – 719 | CarrierSequence analysis2 PublicationsAdd BLAST | 78 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 132 – 520 | AdenylationSequence analysis2 PublicationsAdd BLAST | 389 | |
Regioni | 749 – 1025 | CondensationSequence analysis2 PublicationsAdd BLAST | 277 |
Domaini
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG1178, Eukaryota |
HOGENOMi | CLU_000022_60_3_1 |
InParanoidi | Q4WLW8 |
OMAi | NDTRNAD |
OrthoDBi | 4243at2759 |
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.30.300.30, 1 hit 3.30.559.10, 1 hit 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR010071, AA_adenyl_domain IPR036736, ACP-like_sf IPR045851, AMP-bd_C_sf IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf IPR023213, CAT-like_dom_sf IPR001242, Condensatn IPR009081, PP-bd_ACP |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit PF00668, Condensation, 1 hit PF00550, PP-binding, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit |
TIGRFAMsi | TIGR01733, AA-adenyl-dom, 1 hit |
PROSITEi | View protein in PROSITE PS50075, CARRIER, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MPDLIQTKSV VLGYGVKMVL APAKAARSLL IREEAVWRFS LPRVLSTPTT
60 70 80 90 100
MLETTEPIAH ASELDKPSIV VTNTEVDSED NTSSVLGRYI PQKCLQNARL
110 120 130 140 150
AAVNSCVNEI FEARFRERPD APAVCAWDGS YTYRELNDRS SALAHKLRRR
160 170 180 190 200
GVQAEVLVAL LFEKSKFSVV AMHAVIKAGG AFQLWDPSLP VARLGGMFAE
210 220 230 240 250
SKAHLVLASA ANARLAAEIS ENVMVVDESL VPPWESAPLN PGTQPENALY
260 270 280 290 300
CVFTSGSTGK PKGFLMDHRA FCTCALGVGE LLGLNGASRL IQFSANSFDL
310 320 330 340 350
ATFDHILPFL CGACLCIPSE EERKGDLTRA FNRYRATHAV LTPTVSRLLE
360 370 380 390 400
PEKLTTLQVL LLAGEAPSRE DIRRWASTVG LLNGYSPAEA GCITIVNPSL
410 420 430 440 450
QESHPSKIGF PVSVVPWVVD PDDCNRLVPA GEVGELVLQG HTLARGYFGR
460 470 480 490 500
PDQSKAAFIP TPAWVRQFGY ETYGRLYRTG DLVRFDAEDE SLVYIGRKDS
510 520 530 540 550
QVKIRGQRLE LGEVEHALQQ FFPRPQIVVV ELLTAEDREP ALVGFVYQPG
560 570 580 590 600
SSQHMPAPPQ HQDNSLFLVA DDQFCADAQK ALASLRDILP PYMIPSDLLR
610 620 630 640 650
ISHLPMVPSG KTDRRLIRMR AVDLAPEERR KYSSVLGQSR DQPVTQLEES
660 670 680 690 700
LLGLWATCLK LPPSQIGVLD NFFHLGGGSL EAIHLAAEAR NMGFAELSSA
710 720 730 740 750
AVFQCPTIRE MAGMLDGVTA SVQEQDPRGC TSFQLESSLV AELLRKSQCT
760 770 780 790 800
LEDLQEGFLP LTPFQEKTAK MKPMHLLLDI PGIDHSRLEA AWALVLEKHI
810 820 830 840 850
SFRSIYVEHQ GRVYQAFLRQ PDTVSIPIRW CDEPVHECAA RFCEQDVDLI
860 870 880 890 900
LDGRPWWSMT RINNKIDSVL VLRLTHAQWD ALTLDVLFKD FMAAYESREL
910 920 930 940 950
SRRDLEFPAY MRFRLRHNAS PATVRFWSTF LHGSRLTQPL LLDGAAEVDP
960 970 980 990 1000
GNEAMVFVSQ QIPMLTPPHG ITLGSVFRAA WAFVLARYTG QEDVVFGEFV
1010 1020 1030 1040 1050
EGRSLLVKSV EKVTGCAAAE TPMRIVVSPT ASVRDLLKHS QEQYVARIPY
1060 1070 1080 1090 1100
ETCELEDIVP SSTSWPTDTT FNHILVIQHE PVLPPVALDG RPCPHRWAFH
1110 1120 1130 1140 1150
GRLEDVYVQM VFGPDTLHVG MSGPEIRLSR TIATQLVEKL ASTITQFNDR
1160
PEALLSEITV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAHF01000006 Genomic DNA Translation: EAL89046.1 |
RefSeqi | XP_751084.1, XM_745991.1 |
Genome annotation databases
EnsemblFungii | EAL89046; EAL89046; AFUA_6G12050 |
GeneIDi | 3508389 |
KEGGi | afm:AFUA_6G12050 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAHF01000006 Genomic DNA Translation: EAL89046.1 |
RefSeqi | XP_751084.1, XM_745991.1 |
3D structure databases
SMRi | Q4WLW8 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 746128.CADAFUBP00007607 |
Genome annotation databases
EnsemblFungii | EAL89046; EAL89046; AFUA_6G12050 |
GeneIDi | 3508389 |
KEGGi | afm:AFUA_6G12050 |
Organism-specific databases
VEuPathDBi | FungiDB:Afu6g12050 |
Phylogenomic databases
eggNOGi | KOG1178, Eukaryota |
HOGENOMi | CLU_000022_60_3_1 |
InParanoidi | Q4WLW8 |
OMAi | NDTRNAD |
OrthoDBi | 4243at2759 |
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.30.300.30, 1 hit 3.30.559.10, 1 hit 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR010071, AA_adenyl_domain IPR036736, ACP-like_sf IPR045851, AMP-bd_C_sf IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf IPR023213, CAT-like_dom_sf IPR001242, Condensatn IPR009081, PP-bd_ACP |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit PF00668, Condensation, 1 hit PF00550, PP-binding, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit |
TIGRFAMsi | TIGR01733, AA-adenyl-dom, 1 hit |
PROSITEi | View protein in PROSITE PS50075, CARRIER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FMQC_ASPFU | |
Accessioni | Q4WLW8Primary (citable) accession number: Q4WLW8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 18, 2012 |
Last sequence update: | July 5, 2005 | |
Last modified: | February 23, 2022 | |
This is version 99 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families