ID   MFR6_PHOSM              Reviewed;         419 AA.
AC   A0A3G1DJL2;
DT   18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT   13-FEB-2019, sequence version 1.
DT   25-MAY-2022, entry version 12.
DE   RecName: Full=Squalene synthase R6 {ECO:0000303|PubMed:27056201};
DE            Short=SQS {ECO:0000305};
DE            Short=SS {ECO:0000303|PubMed:27056201};
DE            EC=2.5.1.21 {ECO:0000305|PubMed:27056201};
DE   AltName: Full=Squalestatin S1 biosynthesis cluster protein R6 {ECO:0000303|PubMed:27056201};
GN   Name=R6 {ECO:0000303|PubMed:27056201};
OS   Phoma sp. (strain ATCC 20986 / MF5453).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Didymellaceae; Phoma.
OX   NCBI_TaxID=1828523;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RX   PubMed=27056201; DOI=10.1039/c6cc02130a;
RA   Bonsch B., Belt V., Bartel C., Duensing N., Koziol M., Lazarus C.M.,
RA   Bailey A.M., Simpson T.J., Cox R.J.;
RT   "Identification of genes encoding squalestatin S1 biosynthesis and in vitro
RT   production of new squalestatin analogues.";
RL   Chem. Commun. (Camb.) 52:6777-6780(2016).
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:27056201). 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:27056201,
CC       ECO:0000305|PubMed:27056201}.
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   -!- 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   -!- 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   -!- INDUCTION: Expression is induced on squalestatin S1-producing YMG
CC       medium. {ECO:0000269|PubMed:27056201}.
CC   -!- SIMILARITY: Belongs to the phytoene/squalene synthase family.
CC       {ECO:0000305}.
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DR   EMBL; KU946987; AMY15074.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A3G1DJL2; -.
DR   SMR; A0A3G1DJL2; -.
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   2: Evidence at transcript level;
KW   Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism; Magnesium;
KW   Membrane; Multifunctional enzyme; NADP; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..419
FT                   /note="Squalene synthase R6"
FT                   /id="PRO_0000447843"
FT   TRANSMEM        397..417
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   419 AA;  48180 MW;  A668042133C89887 CRC64;
     MVSARGILYY LSHPQELRPM IQWKVFHGLA HQRDEKNESP DVQACYYYLA LTSRSFVAVC
     QQLDPELLMP ICIFYLVLRG LDTIEDDMTL STEVKEPLLR NFHTTIYDQS WTFHDSGPDE
     KDRELLVHFD CVAREFAKVK DEYKVIITDI TKKMGNGMAD FVVNGELTGV RKIEDYELYC
     HYVAGVVGEG LTRLFVEAKV AEPSLLENPK LIESMGQFLQ QTNIIRDVRE DHDEVRHFWP
     KEVWAKYADD FDQLVSPIPQ NRQKALQCSS EMVLMALNRA DDCLNYISGV REQSVFNFVA
     IPQSMAIATL ELCFQNPAIF DKNIKITKGT ACQLMMDSTQ DMQHVCQAFR RHARRIQKKN
     NPKDPHFHDI NAACNKIERF IDGRYPNLQD EQAKADTMYL VVLLLGILGV AAAVLMAKR