RADS2_FLOCH
ID RADS2_FLOCH Reviewed; 2138 AA.
AC C5H882;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=Non-reducing polyketide synthase rads2 {ECO:0000303|PubMed:19101477};
DE Short=NR-PKS rads2 {ECO:0000303|PubMed:19101477};
DE EC=2.3.1.- {ECO:0000305|PubMed:19101477};
DE AltName: Full=Radicicol biosynthesis cluster protein s2 {ECO:0000303|PubMed:19101477};
GN Name=radS2 {ECO:0000303|PubMed:19101477};
OS Floropilus chiversii (Chaetomium chiversii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Floropilus.
OX NCBI_TaxID=2587399;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP DOMAIN.
RC STRAIN=CS-36-62;
RX PubMed=19101477; DOI=10.1016/j.chembiol.2008.10.006;
RA Wang S., Xu Y., Maine E.A., Wijeratne E.M., Espinosa-Artiles P.,
RA Gunatilaka A.A., Molnar I.;
RT "Functional characterization of the biosynthesis of radicicol, an Hsp90
RT inhibitor resorcylic acid lactone from Chaetomium chiversii.";
RL Chem. Biol. 15:1328-1338(2008).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of radicicol, a resorcylic acid lactone
CC (RAL) that irreversibly inhibits the HSP90 molecular chaperone, an
CC important target for cancer chemotherapy (PubMed:19101477). The cluster
CC encodes only two apparent post-PKS enzymes, a cytochrome P450
CC monooxygenase (radP) and a non-heme halogenase (radH) that introduce
CC the epoxide and the chlorine, respectively (PubMed:19101477). If this
CC cluster includes all the genes required for radicicol biosynthesis, the
CC remaining structural features of radicicol are presumably generated by
CC the PKSs rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise
CC if the R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in
CC contrast to the five iteration-three iteration split for the
CC hypothemycin PKSs (By similarity). The origin of the cis 5',6' double
CC bond is not known (By similarity). The radicicol R-PKS rads1 ER domain
CC may catalyze either double bond isomerization or reduction in the third
CC iteration (By similarity). {ECO:0000250|UniProtKB:B3FWT6,
CC ECO:0000269|PubMed:19101477}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:19101477}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm (By similarity). {ECO:0000250|UniProtKB:Q5B0D0,
CC ECO:0000305|PubMed:19101477}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein (By similarity).
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of radicicol
CC (PubMed:19101477). {ECO:0000269|PubMed:19101477}.
CC -!- BIOTECHNOLOGY: Radicicol is an important pharmacophore as an inhibitor
CC of heat shock protein 90 (Hsp90), an ATP-dependent chaperone involved
CC in the post-translational maturation and stabilization of over one
CC hundred proteins, and which activity has been implicated in diverse
CC pathologies ranging from oncology to neurodegenerative and infectious
CC diseases (PubMed:19101477). {ECO:0000305|PubMed:19101477}.
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DR EMBL; EU980390; ACM42403.1; -; Genomic_DNA.
DR AlphaFoldDB; C5H882; -.
DR SMR; C5H882; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR020802; PKS_thioesterase.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Transferase.
FT CHAIN 1..2138
FT /note="Non-reducing polyketide synthase rads2"
FT /id="PRO_0000443055"
FT DOMAIN 1666..1740
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:19101477"
FT REGION 11..249
FT /note="N-terminal acylcarrier protein transacylase (SAT)
FT domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 376..807
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 901..1184
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 1303..1607
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 1618..1666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1740..1781
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1807..1828
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1860..2006
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT COMPBIAS 1629..1659
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1740..1774
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1807..1826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 549
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 549
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 992
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1700
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2138 AA; 230531 MW; 8295FBAE61C47C3A CRC64;
MRLPQKTKTV LIFGDQTDSW LDGLDQVYKQ AGSTPWLQSF LDDLTDAINA ETKANMLDHA
LQESLGTFST LQELGERYRH TTDELGMAHA LLLHAVRAAT LLQWVKREPN LLGRDGQAEW
LGISGGLITL SARAISEDFD TLRNASLEVA RLFVRLCKFT SVRSRAAEDA PGTWGWAVVG
ISPDELRKRL DEFQQSAGIP SIKRAQVGVT GAGWSTVIGP PSVLEIVMKQ CPAVKSLAKN
PLNIHALQHT IKLSPADLNF IVGNNSAFLD LPLCCPGMNL WGMDEPGATY ANWGEMLKAI
CEQVLSRSLD IPHAVGKVNT KLDGVETIRV IQIGTTSHAP YLLGGLKGPG RHVSVQDAQS
LLQASVSTSS SQSGRIAIVG MAGRGPGCDN VDEFWDLIMS KQDLCREVPK DRFDVDEYYC
PNHGQGDKKC TMTTRFGCFM DKPGNFDSRF FHISPREAML MDPGHRQFLM STYEALEMAG
YSDGHAKATD PTRIAAFYGQ VSDDWHDQSH PTLGCDSYTL QGVQRAFGPG RIAWQFKWEG
PTYSLDSACA STTSSIHLAC MSLLSKDIDM AVAGAANILS FPHSFTCLSK AGVLSDTGNC
KTYRDDADGY CRADFVGTVV LKRLEDAVAH NDNILAVVLS SGRNHSGNST SITTSDAGAQ
ERLFRKVLRN AHVHPDDVSY VEMHGTGTQV GDPAEVGAVG NLFKHRRPAD GPIPVGSVKA
NFGHSEAAAG MASLLKCIKM FQTDTIPPQA GMPHALNPRF PPLSELNIKI PSEPKAFEKL
SKPRRILLNN FDAAGGNACM LLEDYSDTAG TKGADPRSSH VVATSARTQA AHHANRRRLL
EWLRANPTVS IEDVAYTTTA RRMHHPHRFA CTASSTQELI AKLEDSIDAR DTKSSPPSPI
VFVFGGQGSH YGGMGSELYR TSPRFRETVD LCANICEEHG FPSFLHLVTD DGIDMSTATT
VQTQLAVLVL EIGLAAFWKS VGVQPSMVVG HSLGEYAALH VAGVLSLVDV LYLVGRRALL
LLERCEEGAF TMLAVSMTAT AALDFLQSHP QYSSCSVSCI NSPTATVISG STEQIAQLQA
DLTGHSKALP VPYGFHSFQM DSVLADYCTL AEGVTFSAPK IPVASTLLGS VVNKHGTFNG
RYLSQQMRQA VDFVGALNVI KQKLADPIWL ELGPKGVCTS FVRATFSPSS STAEKTLSTL
AGPGPGADNK AASWPPISKC LAALYMQGIA IDWLALHEPY TSCLKMVTLP SYAWDMKDYW
ITYTDANKNA EAAALSPAAT PTAQQMISTC AQYVVQESPS SSKKIQVTFR ASLAESGFGA
IIGGHRMQRE PICPGSAFCE AGFAAAAYVL EANSRKDDAH IAKLVLRHPT MTRPLTKNLV
GPDGELLTTV IMEDASSNEI QVSWRASSAP SKGGLSYDLG SCVLEVRKDV QRLQADWDRT
SYFVKARMDE VVRTAQDGHG HRFQPDIFYI LFAPTVEYDS QYKCIKEAYV SSDFSEAVAE
IELREDPSST RFMASPYWGE SIVHLAGFTV NANPENHLTA SGTSFINSGF ENFEQTVAFE
AGKTYFTYVR VSRKDKGTRS CEVFVFDSDS RMIAQCSGLE FHEISNATLK QVLSGGKSKS
VLKPDNAAPL KAPEKKEDAT PTAPKKSADP GKEEEEEGDT ATPAAVGEFE VIIQTIAIET
GMDTSELTDD SALADLGVDS IMAIEVAARV SNATGRELTP SFVSEYPTIG DLRRAFAMAP
SSSSSTSASE SVSESLDDSS STSRSATPSS SMKETEAGFV EDDSLRKKPV ISAAAAVVTA
AGVAETQATK VQPQAPAATA ADNDSSPAPS VRIMLLQGRP AKSRGAADGS HAPPPFYMIA
DGTGSIATYI HLASSLQSKM PIYGIDSPFL RCPDRLTPEV GIPGAARLIV DALLKKQPDK
DVPFWIGGFS GGAMVAYEVC RQLSAAGRPV DGLLLIDMCA PRQVAAVPED DGEVGLAMFD
AVSGQDESGV WSATDGTRRH LGAMFSCVAT YNPEPLPPRG GGNTPAKRAA MIWARKGMID
RCVSSVRFRQ MLADRGISPE PYPGFMEDPK LGAVAWSLPH KTGADLGPNG WERYLGGDRL
LCMSIEADHL EMPTPGYAQL LGETMDKAFR YFRDGLMD
