SQTKS_PHOSC
ID SQTKS_PHOSC Reviewed; 2603 AA.
AC Q86ZD9;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Squalestatin tetraketide synthase {ECO:0000303|PubMed:15489970};
DE Short=SQTKS {ECO:0000303|PubMed:15489970};
DE EC=2.3.1.- {ECO:0000269|PubMed:15489970};
DE AltName: Full=Highly reducing polyketide synthase 1 {ECO:0000303|PubMed:11251290};
DE Short=HR-PKS 1 {ECO:0000303|PubMed:11251290};
DE AltName: Full=Squalestatin S1 biosynthesis cluster protein pks1 {ECO:0000303|PubMed:15489970};
GN Name=pks1 {ECO:0000303|PubMed:15489970};
OS Phoma sp. (strain C2932).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Didymellaceae; Phoma.
OX NCBI_TaxID=86977;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DOMAIN.
RX PubMed=11251290; DOI=10.1016/s1074-5521(00)90064-4;
RA Nicholson T.P., Rudd B.A., Dawson M., Lazarus C.M., Simpson T.J., Cox R.J.;
RT "Design and utility of oligonucleotide gene probes for fungal polyketide
RT synthases.";
RL Chem. Biol. 8:157-178(2001).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15489970; DOI=10.1039/b411973h;
RA Cox R.J., Glod F., Hurley D., Lazarus C.M., Nicholson T.P., Rudd B.A.,
RA Simpson T.J., Wilkinson B., Zhang Y.;
RT "Rapid cloning and expression of a fungal polyketide synthase gene involved
RT in squalestatin biosynthesis.";
RL Chem. Commun. (Camb.) 2004:2260-2261(2004).
CC -!- FUNCTION: Highly reducing polyketide synthase (HR-PKS); part of the
CC gene cluster that mediates the biosynthesis of squalestatin S1 (SQS1,
CC also known as zaragozic acid A), a lead compound for the treatment of
CC hyper-cholesterolemia by targeting squalene synthase (SS)
CC (PubMed:15489970). Pks1 is responsible for the biosynthesis of the
CC tetraketide sidechain of SQS1 (PubMed:15489970). The biosynthesis must
CC involve 3 rounds of chain extension. After the first and second rounds
CC methyl-transfer occurs, and in all rounds of extension the
CC ketoreductase and dehydratase are active. The enoyl reductase and C-MeT
CC are not active in the final round of extension (PubMed:15489970).
CC {ECO:0000269|PubMed:15489970}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:15489970}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:15489970}.
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DR EMBL; AY217789; AAO62426.1; -; mRNA.
DR AlphaFoldDB; Q86ZD9; -.
DR SMR; Q86ZD9; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
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; 3.40.50.150; -; 1.
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; IPR011032; GroES-like_sf.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
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; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2603
FT /note="Squalestatin tetraketide synthase"
FT /id="PRO_0000447824"
FT DOMAIN 2516..2593
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 32..458
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 463..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..931
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1000..1314
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1465..1665
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1892..2205
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2228..2406
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 464..509
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2553
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2603 AA; 284189 MW; 0F169C69C79777BB CRC64;
MVPYYQPASS CGSNTMAAMD EHQHNEDATI PIAIIGMSCR FPGNATSPEK LWELCAQGRS
AWSSIPKSRF RQEGFYNPNA ERVGTSHVVG GHFLEEDPSL FDASFFNLSA EAAKTMDPQF
RLQLESVYEA MESAGITLEH IAGSDTSVYA GACFRDYHDS LVRDPDLVPR FLLTGNGAAM
SSNRVSHFYD LRGASMTVDT GCSTTLTALH LACQGLRNRE SKTSIVTGAN VILNPDMFVT
MSSLGLLGPE GKSHTFDARA NGYGRGEGIA TVIIKRLDDA LRAQDPIRCI IRGTALNQDG
RTATLTSPSQ TAQSDLIRAC YRAAALDPND TAFLAAHGTG TRTGDAVEIA AAADVFGEKR
SPERPLWIGS VKTNIGHSEA TSGLASVIQA ALALEKGLIP PNINFKEPNE KLGQVSAAVR
VPSNLQKWPS VSGVRRASVN NFGYGGANAH VILESGIPGH TPIANGSGRS NGTGNGHNGA
NGTTNGHNGT NGTTNGHFDA TQATNGHYGT DETPDYAPLD SFVISISAKE EASARSMVTN
LADYLRTLQV QDETKHFKSI AHTLGSHRSM FKWTAAKSIT GPEELIAAAE GGQFQASRAL
ERTRLGFVFT GQGAQWFAMG RELINTYPVF RQSLDRADRY LKEFGCEWSI IDELSRDAEN
SNVNDMTLSP PLCTAVQISL VQLLESWGIV PTAVTGHSSG EIAAAYAAGA LDFKSAMAVT
YFRGEVGLAC QDKIVGKGGM IAVGLGPEDA EDRIARVQSG KIVVACINSQ SSVTVSGDLS
GIVELEDLLK AEGVFARRVK VQAAYHSHHM QVIANGYLTS LKDMLKPTKK FGKIIYSSPT
TGRRETNAKL MASAQHWVNN MLSPVRFAES FQNMCFSNRN SSQSEEIFQD VDIVLEVGPH
GMLQGPIQQM MSLPIFERAR LPYISCLLRG QSAVHTMQTV AAGLMGWGYR VDMVAVNFPQ
GTYGVKILHD LPSYPWNHDN SHWWEPRLNK AHRQRVHPPH DLLGSLIVGR DLREPTWRHF
IRVQDIPWIR DHVVQSALVY PGAGFICMAM EAMVQLHELR DSQSRKVAGY RLAEVDILRA
MLIPDTSEGL EAHISLRPCS TKLLLTNEWY DFCVSSVGDD DKFVDHCRGR ITIEFDTSGS
ADTPRTSLRE RSRSTGLMRS VDPSNLYSFL RAQGIYHGPI FQNLKTISSR KDHSESSFVV
ANTASVMPNG FQSPHVIHPT TLDSIFQGAY TALPGAGLDQ NTAMIPRSIQ ELYLSSALTS
DVGQCLVSDT SLIRYDGQSF TVNVDVSSKA DSEHTPVLEI KGLRNQSVGQ MAPQPGDSSN
NDLCFKLDWA PDISSVKQER LKEKFGFPLD PTEADIIMGL RQACIHFIHR SLQSLTAPDR
DQLDWHQKRF YDWMVLQIQL AEEDRLAPNS SAWLQCSSSD EQKLLENVRA SSVNGQMVVH
VGKSMLAILR HEIAPLELML QDKLLYRYYT DAIKWDRSYQ QIDQLVKLHA HKCPTAKIIE
IGAGTGGCTR AVLDALSNQG IARCAQYDFT DVSSGFFEAA QQKFAAFDDV IRFQKLDIEK
DIEMQGFECG SYDLVIASQV LHATGKMEHT MANVRKLLKP GGKLLLVETT RDEMDLQLVF
GLLPGWWLSS EEERQMSPSL STNSWEKVLK KTGFDGLDIE LRDCDSDEFY SFSVMMATAS
STIASSSMAF AIVYGEVPLP DQFLDDMKTA ISSSAVSDPV VGHLDSIDAT GKFCIFIEDP
ETDILSSPDE KSYASIQKLV TRCKGLIWVS RGGAMHGTRP NSSLKTGLLR TLRLEYTEKR
FISLDLDSAR PQWNHDSITT INEVLCGALA QNADSSIKDS EFAEQDGQLF VPRISCDIAR
NEDLSSDSNS PAQMEPFHQP GKLLQMGIKT PGLIDTLQFS KTDATDNLPN DYIEIEPKAF
GLNFRDVMVA MGQLEESIMG FECAGVVRRV GPSSAGHNIK VGDRVCALLG GQWTNTVRVH
WHSVAPIPQA MDWETAASIP IVFVTAYISL VKIARMQAGE TVLIHAASGG VGQAAIILAK
HVGAEIFATV GTDEKRDLLI KEYKIPDDHI FSSRNALFAK SIRQRTNGKG VDVVLNCLAG
GLLQESFDCL ADFGRFIEIG KRDIELNHCL NMGMFARSAT FTAVDLIAIG RDRSYMFAEA
LPKIMTLLQE KAIRPVTPIS IYKIGDIETA FRLMQAGKHM GKIVITAPED AMVPVITRPP
KLQLRPDASY LIVGGLGGIG RSLCKNFVEN GARSLVLLSR NANVSQQSGE FLDELRSTGC
IVGVVDCDIS SKTQVEATML RLKKDMLPIR GIVHAGMVLQ DSVFERMSLD DYNTAIRPKV
QGSWNLHSGL SDCDLDFFIM LSSLAGVSGS ASQANYTAGG AYQDALAKYR RAQGLSAVSI
DLGMVQSVGY VAETKGVAER LVRMGYSPIS EMEVLKIVEH AITNPPPEAS SAQIITGIST
KPGRHWTESS WLQDARFATL RERARDVKEL SNSQGGAQDK QLAAGQELSM ATSLVEAIDV
VGRAITAKLA TMFLIAAESI IASKSLSEYG VDSLVAVELR NWLAAQLSSD VSVFDVTQSQ
SLTALATTVA TKSSRIDKSL LVA
