UniProtKB - Q4WLW5 (FMQA_ASPFU)
Nonribosomal peptide synthetase fmqA
fmqA
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 PublicationsKineticsi
- KM=18 µM for anthranilate1 Publication
- KM=230 µM for ATP1 Publication
- KM=17 µM for salicylic acid1 Publication
- KM=29 µM for 2-chlorobenzoic acid1 Publication
- KM=32 µM for 4-chlorobenzoic acid1 Publication
- KM=74 µM for benzoic acid1 Publication
- KM=416 µM for 3-aminobenzoic acidATP1 Publication
- KM=1900 µM for 4-aminobenzoic acid1 Publication
: 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
- acyl carrier activity Source: GO_Central
- ligase activity Source: UniProtKB-KW
- phosphopantetheine binding Source: GO_Central
GO - Biological processi
- fumiquinazoline C biosynthetic process Source: AspGD
- nonribosomal peptide biosynthetic process Source: AspGD
- secondary metabolic process Source: AspGD
Keywordsi
Molecular function | Ligase |
Biological process | Virulence |
Names & Taxonomyi
Protein namesi | Recommended name: Nonribosomal peptide synthetase fmqA1 Publication (EC:6.3.2.-1 Publication)Alternative name(s): Fumiquinazoline biosynthesis cluster protein A1 Publication |
Gene namesi | Name:fmqA1 Publication Synonyms:NRPS121 Publication, pesM1 Publication ORF Names:AFUA_6G12080 |
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:Afu6g12080 |
Subcellular locationi
Other locations
- Cytoplasmic vesicle 1 Publication
Note: Does not localize to endocytic vesicles, vacuoles nor mitochondria (PubMed:24612080).1 Publication
Other locations
- cytoplasm Source: GO_Central
- cytoplasmic vesicle Source: AspGD
Keywords - Cellular componenti
Cytoplasmic vesiclePathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000416553 | 1 – 3955 | Nonribosomal peptide synthetase fmqAAdd BLAST | 3955 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 840 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 | |
Modified residuei | 1917 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 | |
Modified residuei | 3459 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 |
Keywords - PTMi
Phosphopantetheine, PhosphoproteinProteomic databases
PRIDEi | Q4WLW5 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Interacts with the mitogen-activated protein kinase mpkA.
1 PublicationProtein-protein interaction databases
STRINGi | 746128.CADAFUBP00007610 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 806 – 879 | Carrier 1PROSITE-ProRule annotation2 PublicationsAdd BLAST | 74 | |
Domaini | 1880 – 1956 | Carrier 2PROSITE-ProRule annotation2 PublicationsAdd BLAST | 77 | |
Domaini | 3422 – 3498 | Carrier 3PROSITE-ProRule annotation2 PublicationsAdd BLAST | 77 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 293 – 691 | Adenylation 1Sequence analysis2 PublicationsAdd BLAST | 399 | |
Regioni | 916 – 1187 | Condensation 1Sequence analysis2 PublicationsAdd BLAST | 272 | |
Regioni | 1371 – 1766 | Adenylation 2Sequence analysis2 PublicationsAdd BLAST | 396 | |
Regioni | 1970 – 2261 | EpimeraseSequence analysis2 PublicationsAdd BLAST | 292 | |
Regioni | 2438 – 2724 | Condensation 2Sequence analysis2 PublicationsAdd BLAST | 287 | |
Regioni | 2906 – 3299 | Adenylation 3Sequence analysis2 PublicationsAdd BLAST | 394 | |
Regioni | 3541 – 3805 | Condensation 3Sequence analysis2 PublicationsAdd BLAST | 265 |
Domaini
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG1176, Eukaryota KOG1178, Eukaryota |
HOGENOMi | CLU_000022_60_4_1 |
InParanoidi | Q4WLW5 |
OMAi | YEWLMAF |
OrthoDBi | 4243at2759 |
Family and domain databases
Gene3Di | 1.10.1200.10, 3 hits 3.30.300.30, 3 hits 3.30.559.10, 4 hits 3.40.50.12780, 3 hits |
InterProi | View protein in InterPro IPR010071, AA_adenyl_domain IPR036736, ACP-like_sf IPR045851, AMP-bd_C_sf IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf IPR023213, CAT-like_dom_sf IPR001242, Condensatn IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR006162, Ppantetheine_attach_site |
Pfami | View protein in Pfam PF00501, AMP-binding, 3 hits PF00668, Condensation, 4 hits PF00550, PP-binding, 3 hits |
SMARTi | View protein in SMART SM00823, PKS_PP, 3 hits |
SUPFAMi | SSF47336, SSF47336, 3 hits |
TIGRFAMsi | TIGR01733, AA-adenyl-dom, 3 hits |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 2 hits PS50075, CARRIER, 3 hits PS00012, PHOSPHOPANTETHEINE, 2 hits |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MERLEAKNQT TKHGERMAPQ RYSVLRDEKC LFPVRNDGKL LVDEWRVTEL
60 70 80 90 100
AISSGEKGLK LCRTTCPTAG ADPRYLAAAA WALLLWRFAE VDTVQIGLQD
110 120 130 140 150
IPPGANEDIL EAGLKRGMKV LAASRRQVQL LNELWQGDTW SISDADPTCY
160 170 180 190 200
SYFDTGIVIC RGNSQDCLAK CRSPNQLRKA NGEACNVLLV LELDLDSNWR
210 220 230 240 250
KCFLAYKTTV LTDIQATHLK SSFEEVVELA RAGRGIPLSE ICLVSRRQLD
260 270 280 290 300
QIGKWNERAL VQPKFKAMHQ VVHDRATDRR HHPAVIAADR ALSYSELETL
310 320 330 340 350
SLKVAYRLRG SGVQPGDLIP VCFCKSSWAI VAMLAINKLG AAFVPLDPSQ
360 370 380 390 400
PVNRLKSITR QLDATLAVTS PENQSLVEDL VTTTVVVSET TVSELVDVHN
410 420 430 440 450
EIVLPACDPG APAYCLFTSG STGKPKGCVV DHAALASVAT HSHALHLGPT
460 470 480 490 500
SRVLQFASFT FGVSLIEVWC TLAAGGTVCL PSDSDRVSRL ADAIRSMGVD
510 520 530 540 550
WCILTPTVLA TLEPEAVPNL RTILVAGEPL KKAQFSLWAE RARLFQAYGF
560 570 580 590 600
TEWAGICCVS PQIRSIGDVG IIGTPANARC WLVEPGNPNQ LAPIGAVAEL
610 620 630 640 650
AVEGPSLAQG YLHDPEKTAA TLIPPPRWRA QYGHADGKRI YTTGDLVYYD
660 670 680 690 700
SNGMLRYVSR KDRQVKIRGQ RIDLAEPEYH IAQACCTIRN VVLDAIVPAD
710 720 730 740 750
SNGDAILVAF VLPSRDESSS NGGHDSPLFA VPDDHFTSSV RQLTSFLEDK
760 770 780 790 800
LPDYMVPRLF LQLKETPVTI TGKIARQKLR EAAEALRHDE LVALAGLETR
810 820 830 840 850
VLPPNTHKET LIHQLVVELL HLPPEMVGMN HNFFSLGGDS VSVMKLVSRA
860 870 880 890 900
KRVGLSFTVK DVFRSPQLGD LARLTDVVNS GAAQHMPPFS LLDRGAQPGL
910 920 930 940 950
LSMAAKICQV ESSMIQDIYP CTPLQEGMMT LSAAKAGSYI ARFVYRLEEH
960 970 980 990 1000
VDSPRFRRAW EMTVEATPIL RTRIISASDG RLYQVVIQEK FRWDDDGQPS
1010 1020 1030 1040 1050
GECVQNGQDR HMLLGEPLTH AALVRDRNQD GSLSTVFVLT MHHSVCDRWS
1060 1070 1080 1090 1100
VGLIMDSVET AYTGQTLTTN SMGPFLQYIQ QLQGGDAFWR SQFVGVKAEV
1110 1120 1130 1140 1150
FPSLPSPEYT PTPTETIDLS VELRDAVPGG HTIANAIRLA WALVISHYTS
1160 1170 1180 1190 1200
CSDVVFGVTI SGRAVPVPDI ERIIGPIIAT VPLRVRLKES STVLEALKAI
1210 1220 1230 1240 1250
QDQSMEMIPF EQLGLRQIRK LSPEAEEACN FQSQLVVQPA WGDENRSLFA
1260 1270 1280 1290 1300
TCEAGAAAEG GFAAYALSMI CQLVGSSQID VRTEFDPKVI QAPIMQRIVH
1310 1320 1330 1340 1350
HFVYTLQYLL AHPDARVAEI PVVSPGEKQL LRQWNGIVPP ASHQCVHEII
1360 1370 1380 1390 1400
QQRQIERPTS TAVWAWDGQL TYAELGELSD RLAEYLATKG VQPEVIVPVC
1410 1420 1430 1440 1450
LEKSYWTTVA MLGISKAGGA FALLDPSQPE QRLQSICHQL NSAVILTSEK
1460 1470 1480 1490 1500
NRDLAGKLAS HPIVLSLQSS RRWGHGPAKQ APATARPDHT LYVAFTSGST
1510 1520 1530 1540 1550
GTPKGVVIEH RSFCTSALAL NRITGVNSES RMLQFAGYSF DGSIMEMLSA
1560 1570 1580 1590 1600
LMAGACVCVP SEFQRRNELV AAAAKFELTH AHLTPSVARH LLRGNPEFTK
1610 1620 1630 1640 1650
TLVSVGEPMT ASDVADWASN GQCKVMNGYG PAECAVSTTI QAAVTSASDP
1660 1670 1680 1690 1700
KNIGFPVAGV CWVVHPENHD ILLPPGAVGE LLIEGPTLAR GYLNEPDKTA
1710 1720 1730 1740 1750
AAFIPLPAWI KDIRPEQPHG RLYKSGDLVR YNADGSFQYI GRRDSQIKLR
1760 1770 1780 1790 1800
GQRIELDEVE KHVYQCWPGV IAVVAVEMVS FTPATQTLVA FVVVEEHVDT
1810 1820 1830 1840 1850
TGDILAAPTQ EFTGQVAVAQ ARLREAIPAF MVPEIFIPLL VLPQSASGKT
1860 1870 1880 1890 1900
DRRRLRSIAT ACTREKLAAY GAVGTGTKRE PTSVAEREMQ AIWAQALNLP
1910 1920 1930 1940 1950
LAEIGMDDSF YQLGGDSITA MQVVAHARSK GLAVTMDSIL RLKSISKIMS
1960 1970 1980 1990 2000
HESSLSPAIV HIDEEEDVWF ALSPIQQMFF DRQPSGWDRF SQVFLLRVSQ
2010 2020 2030 2040 2050
PVTASQLQMA LHTLVSKHPM LRARFAKQHD GSWRQVITSK IQESYRCRSH
2060 2070 2080 2090 2100
RLNRRSSVDG VVSSGACSLS IQKGPLIAVD LMSREDGAQY LSIVIHHLVV
2110 2120 2130 2140 2150
DLVSWRIILA DLEAMLRGEN PMANHSTPFQ TWCRLQAEYA RQYLSPQHAF
2160 2170 2180 2190 2200
PTDLPDHYHQ DPSVFWGLAG QPNLVRDSRR QVFTLDEHTT RQLLGAANAA
2210 2220 2230 2240 2250
FATRTDEVLH AVLLYSFLKV FPHRIAPLTF SEGHGREPWD SAIDLSQTVG
2260 2270 2280 2290 2300
WFTTMWPVVA ELQQNHSFLE VVCRVKDARR AVPCNGWAYF VSRYLNPSGR
2310 2320 2330 2340 2350
QAFQQFHPVE LVFNYAGEYQ QFNQAGAFFI PDMPEYQGSL DAGEQIQRFG
2360 2370 2380 2390 2400
IFEVFASVVR GCLQFQFMYN RYMKHQLEIQ KWIESCRQTL IEGCSTLIAA
2410 2420 2430 2440 2450
KPSRTLSDFP LLPLTYSTLR ELLDVTLPTA GVSVENVEDI YPCSPSQRGM
2460 2470 2480 2490 2500
LIAQAKAAHN YNASVTWSIR SRIDSRPNVA RLKAAWCEVV KRHAILRTVF
2510 2520 2530 2540 2550
VESPWPESYM DQVVLQNVSP EFVFCRGSDS LPQSISSPGQ TRWSKGQCQH
2560 2570 2580 2590 2600
IMRVWERDNG DILCRLDLSH AIMDRTTLAI IQKDLSLAYD ERLLPGRAPL
2610 2620 2630 2640 2650
YRDYISYIYQ QDSESARQYW QGYLEGVEPC EFPTLNPVDP SITKEWGNLY
2660 2670 2680 2690 2700
RTLEDRRRLE EFCRTHSVTP WNVAGLAWAM VLRSFTRTDS VCFGYVKSGR
2710 2720 2730 2740 2750
DLPIDGIAGT AGPVFNPLPC RVHLTERLTV RETIGRLQEE YLQSLAHQSF
2760 2770 2780 2790 2800
PLSDIHRLAG VTSGVLFNTS VAVQTEVASE AEEAKRSLEF TTVAMEDGTE
2810 2820 2830 2840 2850
DDMVITLVPR GGELVLHLRH RSRTLTTDQA STVLATFEKA LCSILANAEA
2860 2870 2880 2890 2900
PMTSIDVFSD HDKAILWSRN RRVPDAVESC VHELIQKHCV ERPHSPAVNA
2910 2920 2930 2940 2950
WDGAFTYGQL DELSSRLAVY LAAQGVGPNV VVPLCFEKTR WTPIAMMGVM
2960 2970 2980 2990 3000
KAGGAFLLLD PSYPLQRLKD ICADIDCRLV VSSTTHEAMS RELASTVVVV
3010 3020 3030 3040 3050
GEDRHHWQLE NTSHTITMPK VRPADALYVV FTSGSTGKPK GVVIEHRSYC
3060 3070 3080 3090 3100
SGALDHIRSY NLTPQSRVLQ FSSYAFDISI VEQLSVLIAG GCICVISESQ
3110 3120 3130 3140 3150
RKNSLGEAAT ALQANHAMLI PSVARLVRHE DLSTITSLSL AGECMQETDV
3160 3170 3180 3190 3200
SYWAQHVRLM NGYGPAECSA LSLVQPCVLP HSDPHDIGYP VGSVAWVVDP
3210 3220 3230 3240 3250
HDHHKLVPNG AVGELLIEGP IVGRGYINNA EKTAEVFIEP PTWLRTLRGH
3260 3270 3280 3290 3300
CTSRLYKTGD LVRANPSGSL SILGRKDRQV KLRGQRLELG EVEANVQHCF
3310 3320 3330 3340 3350
PGALDVVADL LPSSRGGKPQ LVAMVFQNAE RAARIAPESD SKLIAEPSVD
3360 3370 3380 3390 3400
FMQSATTAET RLRQTVPNFM VPSMFLPLAQ IPRTHSDKVD RNSLLKAVAA
3410 3420 3430 3440 3450
MSSIELQAYK ASVDAGHCST RAPSTEEEKK LAEIWADVLK VPVEHIGADD
3460 3470 3480 3490 3500
NFLLSGGDSI DAMKAAAFCR AAGMALSVAD IFAHPVLSDL AKVAVPKSLN
3510 3520 3530 3540 3550
GSSTSHQPFS LSPVDSPKDL HMSLMEQGLV PPGSALADLL PGTQAQQFFI
3560 3570 3580 3590 3600
ERGTFHSYNF SIRGPLDRCR LQKTCTAILS RHSILRTKFL QYEGRLIQIV
3610 3620 3630 3640 3650
LDNLETPFTH YTTDGDLLEF CKSLWERDLA ALDGLGRLPC KFTLVSRSEQ
3660 3670 3680 3690 3700
EHVFTIQISH AQWDGVSIPR LFSDIAAIYN QIPLPSTTHF ADYVYHRSSR
3710 3720 3730 3740 3750
DERPAFDFWK KYLRGSSMPV PFPATNCQDR EHKTQWTFQG IKNPRLPAGI
3760 3770 3780 3790 3800
TMASLVKAAC GFHLCQLLSQ NDVVFGHTVN GRNLALDNVE ALLGCCLNFI
3810 3820 3830 3840 3850
PLRVMLQPSW TVLDLLAHVQ EQYTRALPHE HLELRDIFRH STPWPADTQL
3860 3870 3880 3890 3900
SFIVQHQNIE LHHNIALDGL QVQYSKFAQF DPLTEVWIFS EPHPDRLEIQ
3910 3920 3930 3940 3950
VCANTRVLSE DQARALCRRL CDLIEFFSAS PDCPLSKVVD HMDRPGLLAE
EKVLN
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAHF01000006 Genomic DNA Translation: EAL89049.1 |
RefSeqi | XP_751087.1, XM_745994.1 |
Genome annotation databases
EnsemblFungii | EAL89049; EAL89049; AFUA_6G12080 |
GeneIDi | 3508392 |
KEGGi | afm:AFUA_6G12080 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAHF01000006 Genomic DNA Translation: EAL89049.1 |
RefSeqi | XP_751087.1, XM_745994.1 |
3D structure databases
SMRi | Q4WLW5 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 746128.CADAFUBP00007610 |
Proteomic databases
PRIDEi | Q4WLW5 |
Genome annotation databases
EnsemblFungii | EAL89049; EAL89049; AFUA_6G12080 |
GeneIDi | 3508392 |
KEGGi | afm:AFUA_6G12080 |
Organism-specific databases
VEuPathDBi | FungiDB:Afu6g12080 |
Phylogenomic databases
eggNOGi | KOG1176, Eukaryota KOG1178, Eukaryota |
HOGENOMi | CLU_000022_60_4_1 |
InParanoidi | Q4WLW5 |
OMAi | YEWLMAF |
OrthoDBi | 4243at2759 |
Family and domain databases
Gene3Di | 1.10.1200.10, 3 hits 3.30.300.30, 3 hits 3.30.559.10, 4 hits 3.40.50.12780, 3 hits |
InterProi | View protein in InterPro IPR010071, AA_adenyl_domain IPR036736, ACP-like_sf IPR045851, AMP-bd_C_sf IPR020845, AMP-binding_CS IPR000873, AMP-dep_Synth/Lig IPR042099, ANL_N_sf IPR023213, CAT-like_dom_sf IPR001242, Condensatn IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR006162, Ppantetheine_attach_site |
Pfami | View protein in Pfam PF00501, AMP-binding, 3 hits PF00668, Condensation, 4 hits PF00550, PP-binding, 3 hits |
SMARTi | View protein in SMART SM00823, PKS_PP, 3 hits |
SUPFAMi | SSF47336, SSF47336, 3 hits |
TIGRFAMsi | TIGR01733, AA-adenyl-dom, 3 hits |
PROSITEi | View protein in PROSITE PS00455, AMP_BINDING, 2 hits PS50075, CARRIER, 3 hits PS00012, PHOSPHOPANTETHEINE, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | FMQA_ASPFU | |
Accessioni | Q4WLW5Primary (citable) accession number: Q4WLW5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 18, 2012 |
Last sequence update: | July 5, 2005 | |
Last modified: | February 23, 2022 | |
This is version 110 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