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DADIS_PANGI
ID   DADIS_PANGI             Reviewed;         769 AA.
AC   Q08IT1; A0A0B4U5C5; D2K761; G3M1G1; Q75W18;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   03-AUG-2022, entry version 50.
DE   RecName: Full=Dammarenediol II synthase {ECO:0000303|PubMed:23484102, ECO:0000303|PubMed:29509695, ECO:0000303|Ref.5};
DE            Short=Dammarenediol synthase {ECO:0000303|PubMed:23484102, ECO:0000303|PubMed:29509695, ECO:0000303|Ref.5};
DE            Short=PgDDS {ECO:0000303|PubMed:25981048, ECO:0000303|PubMed:29509695};
DE            EC=4.2.1.125 {ECO:0000269|PubMed:17088293, ECO:0000269|PubMed:23484102};
GN   Name=DDS {ECO:0000303|PubMed:24198659, ECO:0000303|PubMed:29509695};
GN   Synonyms=DS {ECO:0000303|PubMed:23484102, ECO:0000303|PubMed:30577538,
GN   ECO:0000303|Ref.5}, PNA {ECO:0000303|PubMed:29509695};
OS   Panax ginseng (Korean ginseng).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; campanulids; Apiales; Araliaceae; Panax.
OX   NCBI_TaxID=4054;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Root;
RX   PubMed=16962103; DOI=10.1016/j.febslet.2006.08.044;
RA   Tansakul P., Shibuya M., Kushiro T., Ebizuka Y.;
RT   "Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside
RT   biosynthesis, in Panax ginseng.";
RL   FEBS Lett. 580:5143-5149(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP   SPECIFICITY, AND INDUCTION BY METHYL JASMONATE.
RX   PubMed=17088293; DOI=10.1093/pcp/pcl032;
RA   Han J.Y., Kwon Y.S., Yang D.C., Jung Y.R., Choi Y.E.;
RT   "Expression and RNA interference-induced silencing of the dammarenediol
RT   synthase gene in Panax ginseng.";
RL   Plant Cell Physiol. 47:1653-1662(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Han J.Y., Choi Y.E.;
RT   "Dammarenediol synthase gene in Panax ginseng.";
RL   Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   TISSUE=Root;
RX   PubMed=23484102; DOI=10.1155/2013/285740;
RA   Hu W., Liu N., Tian Y., Zhang L.;
RT   "Molecular cloning, expression, purification, and functional
RT   characterization of dammarenediol synthase from Panax ginseng.";
RL   Biomed. Res. Int. 2013:285740-285740(2013).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Hou S., Han M., Liu C., Yang L.;
RT   "Cloning and expression analysis of HMGR, SS, SE, DS, and bAS genes in
RT   Panax ginseng.";
RL   Submitted (JUN-2014) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 390-769.
RA   Wu W.R., Zhou H., Liu L., Huang B.M.;
RT   "Application of nested PCR and direct sequencing to discover single
RT   nucleotide polymorphisms in cDNA sequence of dammaranediol synthase gene of
RT   Panax ginseng.";
RL   Submitted (JUL-2014) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   INDUCED BY HEAVY METAL STRESS.
RX   PubMed=23232757; DOI=10.1007/s00128-012-0891-5;
RA   Balusamy S.R.D., Kim Y.-J., Rahimi S., Senthil K.S., Lee O.R., Lee S.,
RA   Yang D.-C.;
RT   "Transcript pattern of cytochrome P450, antioxidant and ginsenoside
RT   biosynthetic pathway genes under heavy metal stress in Panax ginseng
RT   Meyer.";
RL   Bull. Environ. Contam. Toxicol. 90:194-202(2013).
RN   [8]
RP   INDUCTION BY DCCD.
RX   PubMed=23467002; DOI=10.1016/j.jbiotec.2013.02.012;
RA   Huang C., Qian Z.-G., Zhong J.-J.;
RT   "Enhancement of ginsenoside biosynthesis in cell cultures of Panax ginseng
RT   by N,N'-dicyclohexylcarbodiimide elicitation.";
RL   J. Biotechnol. 165:30-36(2013).
RN   [9]
RP   GENE FAMILY.
RX   PubMed=24198659; DOI=10.5142/jgr.2013.37.332;
RA   Kim D.S., Song M., Kim S.-H., Jang D.-S., Kim J.-B., Ha B.-K., Kim S.H.,
RA   Lee K.J., Kang S.-Y., Jeong I.Y.;
RT   "The improvement of ginsenoside accumulation in Panax ginseng as a result
RT   of gamma-irradiation.";
RL   J. Ginseng Res. 37:332-340(2013).
RN   [10]
RP   INDUCTION BY VANADATE.
RX   DOI=10.1016/j.procbio.2013.05.019;
RA   Huang C., Zhong J.-J.;
RT   "Elicitation of ginsenoside biosynthesis in cell cultures of Panax ginseng
RT   by vanadate.";
RL   Process Biochem. 48:1227-1234(2013).
RN   [11]
RP   INDUCTION BY TWEEN 80.
RX   PubMed=24889095; DOI=10.1002/bab.1256;
RA   Liang Y., Wu J., Li Y., Li J., Ouyang Y., He Z., Zhao S.;
RT   "Enhancement of ginsenoside biosynthesis and secretion by Tween 80 in Panax
RT   ginseng hairy roots.";
RL   Biotechnol. Appl. Biochem. 62:193-199(2015).
RN   [12]
RP   FUNCTION, AND BIOTECHNOLOGY.
RX   PubMed=25981048; DOI=10.1007/s00299-015-1806-9;
RA   Chun J.-H., Adhikari P.B., Park S.-B., Han J.-Y., Choi Y.-E.;
RT   "Production of the dammarene sapogenin (protopanaxadiol) in transgenic
RT   tobacco plants and cultured cells by heterologous expression of PgDDS and
RT   CYP716A47.";
RL   Plant Cell Rep. 34:1551-1560(2015).
RN   [13]
RP   FUNCTION, AND INDUCTION BY ASPERGILLUS NIGER.
RX   PubMed=27746309; DOI=10.1016/j.jbiotec.2016.10.011;
RA   Li J., Liu S., Wang J., Li J., Liu D., Li J., Gao W.;
RT   "Fungal elicitors enhance ginsenosides biosynthesis, expression of
RT   functional genes as well as signal molecules accumulation in adventitious
RT   roots of Panax ginseng C. A. Mey.";
RL   J. Biotechnol. 239:106-114(2016).
RN   [14]
RP   REVIEW.
RX   PubMed=29378087; DOI=10.1002/bab.1649;
RA   Lu J., Li J., Wang S., Yao L., Liang W., Wang J., Gao W.;
RT   "Advances in ginsenoside biosynthesis and metabolic regulation.";
RL   Biotechnol. Appl. Biochem. 65:514-522(2018).
RN   [15]
RP   REVIEW, AND NOMENCLATURE.
RX   PubMed=29509695; DOI=10.3390/molecules23030589;
RA   Yang J.-L., Hu Z.-F., Zhang T.-T., Gu A.-D., Gong T., Zhu P.;
RT   "Progress on the studies of the key enzymes of ginsenoside biosynthesis.";
RL   Molecules 23:0-0(2018).
RN   [16]
RP   DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND INDUCTION BY ABIOTIC FACTORS.
RX   PubMed=30577538; DOI=10.3390/molecules24010014;
RA   Zhang T., Han M., Yang L., Han Z., Cheng L., Sun Z., Yang L.;
RT   "The effects of environmental factors on ginsenoside biosynthetic enzyme
RT   gene expression and saponin abundance.";
RL   Molecules 24:0-0(2018).
CC   -!- FUNCTION: Component of the dammarane-type triterpene saponins (e.g.
CC       ginsenosides or panaxosides) biosynthetic pathway (PubMed:17088293,
CC       PubMed:23484102, PubMed:25981048, PubMed:27746309, PubMed:29378087).
CC       Oxydosqualene cyclase that produces specifically the 20S isomer of the
CC       triterpene dammarenediol II (PubMed:17088293, PubMed:23484102,
CC       PubMed:25981048). {ECO:0000269|PubMed:17088293,
CC       ECO:0000269|PubMed:23484102, ECO:0000269|PubMed:25981048,
CC       ECO:0000269|PubMed:27746309, ECO:0000303|PubMed:29378087}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dammarenediol-II = (S)-2,3-epoxysqualene + H2O;
CC         Xref=Rhea:RHEA:30855, ChEBI:CHEBI:15377, ChEBI:CHEBI:15441,
CC         ChEBI:CHEBI:62416; EC=4.2.1.125;
CC         Evidence={ECO:0000269|PubMed:17088293, ECO:0000269|PubMed:23484102};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30857;
CC         Evidence={ECO:0000269|PubMed:23484102};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P48449}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P48449}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in flower buds, leaves, stems, petioles
CC       and roots. {ECO:0000269|PubMed:17088293, ECO:0000269|PubMed:30577538}.
CC   -!- DEVELOPMENTAL STAGE: Rapid decrease in leaves from the leaf opened to
CC       the green fruit stage (PubMed:30577538). Slight increase in roots from
CC       the leaf opened to the green fruit stage (PubMed:30577538).
CC       {ECO:0000269|PubMed:30577538}.
CC   -!- INDUCTION: Up-regulated by methyl jasmonate (PubMed:17088293). Induced
CC       by N,N'-dicyclohexylcarbodiimide (DCCD) in a nitric oxide (NO)
CC       dependent manner thus leading to increased ginsenosides accumulation
CC       (PubMed:23467002). Induced by A.niger mycelium-derived elicitor, thus
CC       improving ginsenosides production in adventitious roots culture
CC       (PubMed:27746309). Triggered by vanadate (Ref.10). Induced by Tween 80
CC       (PubMed:24889095). Accumulates under heavy metal stress in the presence
CC       of CuCl(2) and CdCl(2) (PubMed:23232757). Influenced in roots and
CC       leaves by relative humidity and photosynthetically active radiation
CC       (PAR), and in leaves by rain (PubMed:30577538).
CC       {ECO:0000269|PubMed:17088293, ECO:0000269|PubMed:23232757,
CC       ECO:0000269|PubMed:23467002, ECO:0000269|PubMed:24889095,
CC       ECO:0000269|PubMed:27746309, ECO:0000269|PubMed:30577538,
CC       ECO:0000269|Ref.10}.
CC   -!- BIOTECHNOLOGY: Transgenic tobacco plants coexpressing PgDDS and
CC       PgPPDS1/CYP716A47 accumulate dammarene sapogenin (protopanaxadiol,
CC       PPD). {ECO:0000269|PubMed:25981048}.
CC   -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC       {ECO:0000305}.
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DR   EMBL; AB265170; BAF33291.1; -; mRNA.
DR   EMBL; AB122080; BAD15332.1; -; mRNA.
DR   EMBL; GU183405; ACZ71036.1; -; mRNA.
DR   EMBL; JN596111; AEO27862.1; -; mRNA.
DR   EMBL; KJ939266; AJV26447.1; -; mRNA.
DR   EMBL; KM232664; AJC01927.1; -; mRNA.
DR   EMBL; KM232668; AJC01931.1; -; mRNA.
DR   AlphaFoldDB; Q08IT1; -.
DR   SMR; Q08IT1; -.
DR   KEGG; ag:BAF33291; -.
DR   BioCyc; MetaCyc:MON-13444; -.
DR   BRENDA; 4.2.1.125; 7895.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005811; C:lipid droplet; IEA:InterPro.
DR   GO; GO:0016866; F:intramolecular transferase activity; IEA:InterPro.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0010038; P:response to metal ion; IEP:UniProtKB.
DR   GO; GO:0002238; P:response to molecule of fungal origin; IEP:UniProtKB.
DR   GO; GO:1902438; P:response to vanadate(3-); IEP:UniProtKB.
DR   GO; GO:0016135; P:saponin biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0016104; P:triterpenoid biosynthetic process; IDA:UniProtKB.
DR   CDD; cd02892; SQCY_1; 1.
DR   InterPro; IPR032696; SQ_cyclase_C.
DR   InterPro; IPR032697; SQ_cyclase_N.
DR   InterPro; IPR018333; Squalene_cyclase.
DR   InterPro; IPR002365; Terpene_synthase_CS.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   PANTHER; PTHR11764; PTHR11764; 1.
DR   Pfam; PF13243; SQHop_cyclase_C; 1.
DR   Pfam; PF13249; SQHop_cyclase_N; 1.
DR   SFLD; SFLDG01016; Prenyltransferase_Like_2; 1.
DR   SUPFAM; SSF48239; SSF48239; 2.
DR   TIGRFAMs; TIGR01787; squalene_cyclas; 1.
DR   PROSITE; PS01074; TERPENE_SYNTHASES; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Isomerase; Isoprene biosynthesis; Lyase; Membrane;
KW   Repeat; Transmembrane; Transmembrane helix.
FT   CHAIN           1..769
FT                   /note="Dammarenediol II synthase"
FT                   /id="PRO_0000412837"
FT   TRANSMEM        612..632
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REPEAT          457..501
FT                   /note="PFTB 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          518..563
FT                   /note="PFTB 2"
FT                   /evidence="ECO:0000255"
FT   REPEAT          595..635
FT                   /note="PFTB 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          644..685
FT                   /note="PFTB 4"
FT                   /evidence="ECO:0000255"
FT   REPEAT          706..747
FT                   /note="PFTB 5"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        488
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            421
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            477
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   SITE            616
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P48449"
FT   CONFLICT        4..6
FT                   /note="QKG -> LKV (in Ref. 3; ACZ71036 and 2; BAD15332)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        6
FT                   /note="G -> V (in Ref. 4; AEO27862 and 5; AJV26447)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        310
FT                   /note="N -> I (in Ref. 2; BAD15332)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        446
FT                   /note="A -> V (in Ref. 2; BAD15332)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   769 AA;  88343 MW;  16B4C0F7FC58EC73 CRC64;
     MWKQKGAQGN DPYLYSTNNF VGRQYWEFQP DAGTPEEREE VEKARKDYVN NKKLHGIHPC
     SDMLMRRQLI KESGIDLLSI PPLRLDENEQ VNYDAVTTAV KKALRLNRAI QAHDGHWPAE
     NAGSLLYTPP LIIALYISGT IDTILTKQHK KELIRFVYNH QNEDGGWGSY IEGHSTMIGS
     VLSYVMLRLL GEGLAESDDG NGAVERGRKW ILDHGGAAGI PSWGKTYLAV LGVYEWEGCN
     PLPPEFWLFP SSFPFHPAKM WIYCRCTYMP MSYLYGKRYH GPITDLVLSL RQEIYNIPYE
     QIKWNQQRHN CCKEDLYYPH TLVQDLVWDG LHYFSEPFLK RWPFNKLRKR GLKRVVELMR
     YGATETRFIT TGNGEKALQI MSWWAEDPNG DEFKHHLARI PDFLWIAEDG MTVQSFGSQL
     WDCILATQAI IATNMVEEYG DSLKKAHFFI KESQIKENPR GDFLKMCRQF TKGAWTFSDQ
     DHGCVVSDCT AEALKCLLLL SQMPQDIVGE KPEVERLYEA VNVLLYLQSR VSGGFAVWEP
     PVPKPYLEML NPSEIFADIV VEREHIECTA SVIKGLMAFK CLHPGHRQKE IEDSVAKAIR
     YLERNQMPDG SWYGFWGICF LYGTFFTLSG FASAGRTYDN SEAVRKGVKF FLSTQNEEGG
     WGESLESCPS EKFTPLKGNR TNLVQTSWAM LGLMFGGQAE RDPTPLHRAA KLLINAQMDN
     GDFPQQEITG VYCKNSMLHY AEYRNIFPLW ALGEYRKRVW LPKHQQLKI
 
 
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