CLZ20_COCLU
ID CLZ20_COCLU Reviewed; 415 AA.
AC A0A345BJQ0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 25-MAY-2022, entry version 14.
DE RecName: Full=Squalene synthase clz20 {ECO:0000303|PubMed:28605916};
DE Short=SQS clz20 {ECO:0000305};
DE Short=SS clz20 {ECO:0000303|PubMed:28605916};
DE EC=2.5.1.21 {ECO:0000305|PubMed:28605916};
DE AltName: Full=Squalestatin S1 biosynthesis cluster protein clz20 {ECO:0000303|PubMed:28605916};
DE AltName: Full=Zaragozic acid A biosynthesis cluster protein 20 {ECO:0000303|PubMed:28605916};
DE Flags: Fragment;
GN Name=clz20 {ECO:0000303|PubMed:28605916};
OS Cochliobolus lunatus (Filamentous fungus) (Curvularia lunata).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae; Curvularia.
OX NCBI_TaxID=5503;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 74067;
RX PubMed=28605916; DOI=10.1021/acs.orglett.7b01534;
RA Liu N., Hung Y.S., Gao S.S., Hang L., Zou Y., Chooi Y.H., Tang Y.;
RT "Identification and heterologous production of a benzoyl-primed
RT tricarboxylic acid polyketide intermediate from the zaragozic acid A
RT biosynthetic pathway.";
RL Org. Lett. 19:3560-3563(2017).
CC -!- FUNCTION: Squalene synthase; part of the gene cluster that mediates the
CC biosynthesis of squalestatin S1 (SQS1, also known as zaragozic acid A),
CC a heavily oxidized fungal polyketide that offers potent cholesterol
CC lowering activity by targeting squalene synthase (SS)
CC (PubMed:28605916). Catalyzes the condensation of 2 two farnesyl
CC pyrophosphate moieties to form squalene (By similarity). The presence
CC of a gene encoding a squalene synthase supports the identification of
CC the cluster as being responsible for SQS1 production and suggests a
CC likely mechanism for self-resistance (Probable).
CC {ECO:0000250|UniProtKB:P29704, ECO:0000269|PubMed:28605916,
CC ECO:0000305|PubMed:28605916}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADH = 2 diphosphate +
CC NAD(+) + squalene; Xref=Rhea:RHEA:32299, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (2E,6E)-farnesyl diphosphate + H(+) + NADPH = 2 diphosphate
CC + NADP(+) + squalene; Xref=Rhea:RHEA:32295, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15440, ChEBI:CHEBI:33019, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:175763; EC=2.5.1.21;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P29704};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 1/3. {ECO:0000250|UniProtKB:P29704}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC {ECO:0000305}.
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DR EMBL; MF806533; AXF50663.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A345BJQ0; -.
DR SMR; A0A345BJQ0; -.
DR UniPathway; UPA00767; UER00751.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004310; F:farnesyl-diphosphate farnesyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0051996; F:squalene synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00683; Trans_IPPS_HH; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR002060; Squ/phyt_synthse.
DR InterPro; IPR006449; Squal_synth-like.
DR InterPro; IPR019845; Squalene/phytoene_synthase_CS.
DR InterPro; IPR044844; Trans_IPPS_euk-type.
DR InterPro; IPR033904; Trans_IPPS_HH.
DR PANTHER; PTHR11626; PTHR11626; 1.
DR Pfam; PF00494; SQS_PSY; 1.
DR SFLD; SFLDG01018; Squalene/Phytoene_Synthase_Lik; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR TIGRFAMs; TIGR01559; squal_synth; 1.
DR PROSITE; PS01044; SQUALEN_PHYTOEN_SYN_1; 1.
DR PROSITE; PS01045; SQUALEN_PHYTOEN_SYN_2; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Membrane; Multifunctional enzyme; NADP; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..>415
FT /note="Squalene synthase clz20"
FT /id="PRO_0000452640"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT NON_TER 415
FT /evidence="ECO:0000305"
SQ SEQUENCE 415 AA; 47890 MW; F61559D3BD8B50BC CRC64;
MVSTRGVLYY LLRPKELRPI LQWKALHGLG HQRDEKNESP DVKACYQYLA LTSRSFAAVC
QQLDRELLMP ICIFYLILRG LDTIEDDMTL SKEVKEPLLR NFYTTIYDQT WTFNDSGTDE
KDRELLVHFD CVAREFHKIK DEYKIIITDI TKQMGNGMAD FVVSGDLTGI QKIKDYELYC
HYVAGVVGDG LTRLFVEANV ADPSLLKNPR LIESMGQFLQ QTNIIRDVRE DHDEVRHFWP
KEVWSKYAQD FDHLVSPKPQ DRKKALQCSS EMVLMALNRA DDCLNYMAGV REQTVFNFVA
IPQSMAIATL ELCFQNPAIF DKNIKITKGA TCQLMIDSTQ DLQHVCQAFR RYARRIKKKN
HPEDPHFHDI NAACNKIDRF IDDRYPNLQD EQAKADTMYL AVLVLGVFGV VAAIL
