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GTPSC_THYCA
ID   GTPSC_THYCA             Reviewed;         597 AA.
AC   R4JQT5; R4JGM8; R4JJJ6;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 2.
DT   03-AUG-2022, entry version 31.
DE   RecName: Full=Gamma-terpinene synthase, chloroplastic {ECO:0000303|PubMed:23624978};
DE            EC=4.2.3.114 {ECO:0000269|PubMed:23624978};
DE   AltName: Full=Terpene synthase 2 {ECO:0000303|PubMed:23624978};
DE            Short=TcTPS2 {ECO:0000303|PubMed:23624978};
DE   Flags: Precursor;
GN   Name=TPS2 {ECO:0000303|PubMed:23624978};
OS   Thymus caespititius (Cretan thyme) (Origanum caespititium).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   asterids; lamiids; Lamiales; Lamiaceae; Nepetoideae; Mentheae; Thymus.
OX   NCBI_TaxID=751871;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION,
RP   CATALYTIC ACTIVITY, AND PATHWAY.
RC   STRAIN=cv. C2; TISSUE=Flower;
RX   PubMed=23624978; DOI=10.1007/s00425-013-1884-2;
RA   Lima A.S., Schimmel J., Lukas B., Novak J., Barroso J.G., Figueiredo A.C.,
RA   Pedro L.G., Degenhardt J., Trindade H.;
RT   "Genomic characterization, molecular cloning and expression analysis of two
RT   terpene synthases from Thymus caespititius (Lamiaceae).";
RL   Planta 238:191-204(2013).
RN   [2]
RP   REVIEW ON CARVACROL, AND BIOTECHNOLOGY.
RX   PubMed=24915411; DOI=10.1080/10408398.2011.653458;
RA   Suntres Z.E., Coccimiglio J., Alipour M.;
RT   "The bioactivity and toxicological actions of carvacrol.";
RL   Crit. Rev. Food Sci. Nutr. 55:304-318(2015).
RN   [3]
RP   REVIEW ON THYMOL, AND BIOTECHNOLOGY.
RX   PubMed=29785774; DOI=10.1002/ptr.6109;
RA   Salehi B., Mishra A.P., Shukla I., Sharifi-Rad M., Contreras M.D.M.,
RA   Segura-Carretero A., Fathi H., Nasrabadi N.N., Kobarfard F.,
RA   Sharifi-Rad J.;
RT   "Thymol, thyme, and other plant sources: Health and potential uses.";
RL   Phytother. Res. 32:1688-1706(2018).
RN   [4]
RP   REVIEW ON CARVACROL AND THYMOL, AND BIOTECHNOLOGY.
RX   PubMed=29874939; DOI=10.1080/14786419.2018.1480618;
RA   Wang K., Jiang S., Yang Y., Fan L., Su F., Ye M.;
RT   "Synthesis and antifungal activity of carvacrol and thymol esters with
RT   heteroaromatic carboxylic acids.";
RL   Nat. Prod. Res. 33:1924-1930(2019).
RN   [5]
RP   REVIEW ON CARVACROL EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX   PubMed=33664752; DOI=10.3389/fpls.2020.601335;
RA   Javed H., Meeran M.F.N., Jha N.K., Ojha S.;
RT   "Carvacrol, a plant metabolite targeting viral protease (Mpro) and ACE2 in
RT   host cells can be a possible candidate for COVID-19.";
RL   Front. Plant Sci. 11:601335-601335(2020).
RN   [6]
RP   REVIEW ON CARVACROL EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX   PubMed=32448034; DOI=10.1080/07391102.2020.1772112;
RA   Kumar A., Choudhir G., Shukla S.K., Sharma M., Tyagi P., Bhushan A.,
RA   Rathore M.;
RT   "Identification of phytochemical inhibitors against main protease of COVID-
RT   19 using molecular modeling approaches.";
RL   J. Biomol. Struct. Dyn. 4:1-11(2020).
RN   [7]
RP   REVIEW ON CARVACROL DERIVATIVES, AND BIOTECHNOLOGY.
RX   PubMed=30836858; DOI=10.1080/07391102.2019.1590243;
RA   Zengin Kurt B., Durdagi S., Celebi G., Ekhteiari Salmas R., Sonmez F.;
RT   "Synthesis, anticholinesterase activity and molecular modeling studies of
RT   novel carvacrol-substituted amide derivatives.";
RL   J. Biomol. Struct. Dyn. 38:841-859(2020).
RN   [8]
RP   REVIEW ON PLANT ESSENTIAL OILS EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX   PubMed=32834111; DOI=10.1016/j.molstruc.2020.128823;
RA   Kulkarni S.A., Nagarajan S.K., Ramesh V., Palaniyandi V., Selvam S.P.,
RA   Madhavan T.;
RT   "Computational evaluation of major components from plant essential oils as
RT   potent inhibitors of SARS-CoV-2 spike protein.";
RL   J. Mol. Struct. 1221:128823-128823(2020).
RN   [9]
RP   REVIEW ON PLANT ESSENTIAL OILS EFFECTS ON COVID-19, AND BIOTECHNOLOGY.
RX   PubMed=33855010; DOI=10.3389/fchem.2021.642026;
RA   Yadalam P.K., Varatharajan K., Rajapandian K., Chopra P., Arumuganainar D.,
RA   Nagarathnam T., Sohn H., Madhavan T.;
RT   "Antiviral essential oil components against SARS-CoV-2 in pre-procedural
RT   mouth rinses for dental settings during COVID-19: A computational study.";
RL   Front. Chem. 9:642026-642026(2021).
CC   -!- FUNCTION: Involved in the biosynthesis of phenolic monoterpenes natural
CC       products thymol and carvacrol which have a broad range of biological
CC       activities acting as antimicrobial compounds, insecticides,
CC       antioxidants and pharmaceutical agents (PubMed:23624978). Monoterpene
CC       synthase which catalyzes the conversion of geranyl diphosphate (GPP) to
CC       gamma-terpinene and minor amounts of other monoterpenes (e.g. alpha-
CC       thujene, alpha-terpinene, myrcene, sabinene, (+)-R-limonene, alpha-
CC       pinene and alpha-phellandrene) (PubMed:23624978).
CC       {ECO:0000269|PubMed:23624978}.
CC   -!- CATALYTIC ACTIVITY: [Gamma-terpinene synthase, chloroplastic]:
CC       Reaction=(2E)-geranyl diphosphate = diphosphate + gamma-terpinene;
CC         Xref=Rhea:RHEA:32559, ChEBI:CHEBI:10577, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:58057; EC=4.2.3.114;
CC         Evidence={ECO:0000269|PubMed:23624978};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32560;
CC         Evidence={ECO:0000269|PubMed:23624978};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:E2E2P0};
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:E2E2P0};
CC       Note=Binds 3 Mg(2+) or Mn(2+) ions per subunit.
CC       {ECO:0000250|UniProtKB:E2E2P0};
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:23624978}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:A0A0M3Q1Q3}.
CC   -!- SUBCELLULAR LOCATION: Plastid, chloroplast {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=R4JQT5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=R4JQT5-2; Sequence=VSP_061121;
CC   -!- DOMAIN: The Asp-Asp-Xaa-Xaa-Asp/Glu (DDXXD/E) motif is important for
CC       the catalytic activity, presumably through binding to Mg(2+).
CC       {ECO:0000250|UniProtKB:Q9X839}.
CC   -!- BIOTECHNOLOGY: The monoterpenic phenol thymol is widely used as a
CC       fragrance and a flavoring ingredient in food and cosmetic industries
CC       (PubMed:29785774). Its derivatives have also several biological and
CC       pharmacological properties such as antimicrobial, antioxidant,
CC       anticarcinogenesis, anti-inflammatory and antispasmodic activities
CC       (PubMed:29785774, PubMed:29874939). Medical applications include the
CC       treatment of disorders affecting the respiratory, nervous, and
CC       cardiovascular systems (PubMed:29785774). It may also act as a growth
CC       enhancer and immunomodulator (PubMed:29785774). Thymol may also have
CC       antiviral activity toward COVID-19 by binding to the S1 receptor
CC       binding domain of the SARS-CoV-2 spike (S) glycoprotein
CC       (PubMed:32834111, PubMed:33855010). {ECO:0000303|PubMed:29785774,
CC       ECO:0000303|PubMed:29874939, ECO:0000303|PubMed:32834111,
CC       ECO:0000303|PubMed:33855010}.
CC   -!- BIOTECHNOLOGY: The monoterpenic phenol carvacrol is commonly used as a
CC       fragrance and a food flavoring ingredient and preservative
CC       (PubMed:24915411). Its derivatives exhibit also various biological and
CC       pharmacological properties including antioxidant, antibacterial,
CC       antifungal, insecticid, nematicid, anticancer, anti-inflammatory,
CC       hepatoprotective, spasmolytic, and vasorelaxant (PubMed:24915411,
CC       PubMed:29874939, PubMed:30836858, PubMed:33664752). Phytochemical
CC       inhibitor targeting the main SARS-CoV-2 viral protease (Mpro) and ACE2
CC       in human host cells, carvacrol is a possible candidate for treating
CC       COVID-19 (PubMed:33664752, PubMed:32448034). Carvacrol may also have
CC       antiviral activity toward COVID-19 by binding to the S1 receptor
CC       binding domain of the SARS-CoV-2 spike (S) glycoprotein
CC       (PubMed:32834111, PubMed:33855010). {ECO:0000303|PubMed:24915411,
CC       ECO:0000303|PubMed:29874939, ECO:0000303|PubMed:30836858,
CC       ECO:0000303|PubMed:32448034, ECO:0000303|PubMed:32834111,
CC       ECO:0000303|PubMed:33664752, ECO:0000303|PubMed:33855010}.
CC   -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR   EMBL; KC691293; AGK88261.1; -; Genomic_DNA.
DR   EMBL; KC691294; AGK88262.1; -; mRNA.
DR   EMBL; KC691295; AGK88263.1; -; mRNA.
DR   SMR; R4JQT5; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0009507; C:chloroplast; IEA:UniProtKB-SubCell.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0010333; F:terpene synthase activity; IEA:InterPro.
DR   GO; GO:0016102; P:diterpenoid biosynthetic process; IEA:InterPro.
DR   CDD; cd00684; Terpene_cyclase_plant_C1; 1.
DR   Gene3D; 1.10.600.10; -; 1.
DR   Gene3D; 1.50.10.130; -; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR034741; Terpene_cyclase-like_1_C.
DR   InterPro; IPR044814; Terpene_cyclase_plant_C1.
DR   InterPro; IPR001906; Terpene_synth_N.
DR   InterPro; IPR036965; Terpene_synth_N_sf.
DR   InterPro; IPR005630; Terpene_synthase_metal-bd.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   Pfam; PF01397; Terpene_synth; 1.
DR   Pfam; PF03936; Terpene_synth_C; 1.
DR   SFLD; SFLDG01019; Terpene_Cyclase_Like_1_C_Termi; 1.
DR   SUPFAM; SSF48239; SSF48239; 1.
DR   SUPFAM; SSF48576; SSF48576; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chloroplast; Lyase; Magnesium; Manganese;
KW   Metal-binding; Plastid; Transit peptide.
FT   TRANSIT         1..47
FT                   /note="Chloroplast"
FT                   /evidence="ECO:0000255"
FT   CHAIN           48..597
FT                   /note="Gamma-terpinene synthase, chloroplastic"
FT                   /id="PRO_0000453307"
FT   REGION          356..362
FT                   /note="Homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0M3Q1Q3"
FT   REGION          428..464
FT                   /note="Homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:A0A0M3Q1Q3"
FT   MOTIF           350..354
FT                   /note="DDXXD motif"
FT                   /evidence="ECO:0000250|UniProtKB:Q9X839"
FT   BINDING         350
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   BINDING         350
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   BINDING         354
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   BINDING         354
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   BINDING         494
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   BINDING         502
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1C9J6A7"
FT   VAR_SEQ         1..50
FT                   /note="MATLSMQVSILNKQLKNLNSFGMRASKLPLVARRVDVSTTRLRPICSASQ
FT                   -> MASL (in isoform 2)"
FT                   /id="VSP_061121"
FT   CONFLICT        3..4
FT                   /note="TL -> PP (in Ref. 1; AGK88262)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        12..15
FT                   /note="NKQL -> SKQV (in Ref. 1; AGK88262)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        30
FT                   /note="L -> M (in Ref. 1; AGK88262)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        50
FT                   /note="Q -> L (in Ref. 1; AGK88262)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   597 AA;  69296 MW;  92C597CDC04FDABC CRC64;
     MATLSMQVSI LNKQLKNLNS FGMRASKLPL VARRVDVSTT RLRPICSASQ QVEEETRRSG
     NYQASIWDNA FIQSFNTNKY RDEKHLNRKE ELIAQVKVLL NTKMEAVKQL ELIDDLRNLG
     LTYYFQDEFK KILTCIYNDH KCFKNEQVGD LYFTSLGFRL LRLHGFDVSE EVFSFFKNED
     GSDFKASLGE NTKDVLQLYE ASFLVRVGEV TLEQARVFST KILEKKVDEG INDEKLLAWI
     QHSLALPLHW RIQRLEARWF LDAYAARKDM NPLIFELGKI DFHIIQETQL EEVQEVSRWW
     TNSNLAEKLP FVRDRIVECY FWALGLFEPH EYGYQRKMAA IIITFVTIID DVYDVYGTLD
     ELQLFTDAIR KWDFESISTL PYYMQVCYLA LYTYASELAY DILKDQGFNS ISYLQRSWLS
     LVEGFFQEAK WYYAGYTPTL AEYLENAKVS ISSPTIISQV YFTLPNSTER TVVENVYGYH
     NILYLSGMIL RLADDLGTTQ FELKRGDVQK AIQCYMKDNN ATEKEGQEHV KYLLLEAWKE
     MNTAMADPDC PLSEDLVDAA ANLGRASQFI YLEGDGHGVQ HSEIHNQMGG LIFEPYV
 
 
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