UniProtKB - Q8GTB6 (THCAS_CANSA)
Protein
Tetrahydrocannabinolic acid synthase
Gene
N/A
Organism
Cannabis sativa (Hemp) (Marijuana)
Status
Functioni
Catalyzes the oxidative cyclization of the monoterpene moiety in cannabigerolic acid (CBGA), producing delta9-tetrahydrocannabinolate (THCA), the major cannabioid in drug-type Cannabis plants. Can also use cannabinerolic acid as substrate, but not cannabigerol or cannabinerol.1 Publication
Miscellaneous
THCA synthase might contribute to the self-defense of Cannabis plants by producing both THCA and hydrogen peroxide, but since these reaction products are toxic to the plant itself, THCA synthase must be secreted from secretory cells into the storage cavity to avoid cellular damage.
Catalytic activityi
- EC:1.21.3.73 Publications
Cofactori
FAD1 PublicationNote: Binds 1 FAD per subunit in a bicovalent manner.1 Publication
Activity regulationi
Inhibited by Hg2+.1 Publication
Kineticsi
kcat is 0.30 sec(-1) for cannabigerolate.
- KM=134 µM for cannabigerolic acid2 Publications
- KM=254 µM for cannabinerolic acid2 Publications
- Vmax=2.68 nmol/sec/mg enzyme with cannabigerolic acid as substrate2 Publications
- Vmax=0.37 nmol/sec/mg enzyme with cannabinerolic acid as substrate2 Publications
pH dependencei
Optimum pH is 5.5-6.0.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 114 | FAD (covalent; via 2 links, pros nitrogen)1 Publication | 1 | |
Binding sitei | 176 | FAD (covalent; via 2 links)1 Publication | 1 | |
Binding sitei | 292 | SubstrateCurated | 1 | |
Binding sitei | 417 | SubstrateCurated | 1 | |
Active sitei | 484 | Proton acceptorCurated | 1 |
GO - Molecular functioni
- Delta9-tetrahydrocannabinolate synthase activity Source: UniProtKB-EC
- FAD binding Source: InterPro
Keywordsi
Molecular function | Oxidoreductase |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-12033 |
BRENDAi | 1.21.3.7 1159 |
Names & Taxonomyi
Protein namesi | Recommended name: Tetrahydrocannabinolic acid synthase (EC:1.21.3.7)Short name: THCAS Alternative name(s): Delta(1)-tetrahydrocannabinolic acid synthase THCA synthase |
Organismi | Cannabis sativa (Hemp) (Marijuana) |
Taxonomic identifieri | 3483 [NCBI] |
Taxonomic lineagei | Eukaryota › Viridiplantae › Streptophyta › Embryophyta › Tracheophyta › Spermatophyta › Magnoliopsida › eudicotyledons › Gunneridae › Pentapetalae › rosids › fabids › Rosales › Cannabaceae › Cannabis |
Subcellular locationi
Extracellular region or secreted
- apoplast Source: UniProtKB-SubCell
Keywords - Cellular componenti
Apoplast, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 92 | H → A: No effect. 1 Publication | 1 | |
Mutagenesisi | 108 | R → A: Strongly reduced catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 110 | R → A: Strongly reduced catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 114 | H → A: Loss of FAD binding and loss of catalytic activity. 2 Publications | 1 | |
Mutagenesisi | 208 | H → A: No effect. 1 Publication | 1 | |
Mutagenesisi | 292 | H → A: Strongly reduced catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 417 | Y → F: Reduced catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 442 | E → Q: Slightly reduced catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 484 | Y → F: Loss of catalytic activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | 2 PublicationsAdd BLAST | 28 | |
ChainiPRO_0000421142 | 29 – 545 | Tetrahydrocannabinolic acid synthaseAdd BLAST | 517 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 37 ↔ 99 | 1 Publication | ||
Glycosylationi | 65 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 89 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 168 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 297 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 305 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 329 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 467 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 499 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Glycosylated when produced in a heterologous system. The deglycosylated THCA synthase has more catalytic activity than the glycosylated form.2 Publications
The FAD cofactor is bound via a bicovalent 6-S-cysteinyl, 8alpha-N1-histidyl FAD linkage.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PRIDEi | Q8GTB6 |
Expressioni
Tissue specificityi
Expressed in the secretory cells of glandular trichomes.1 Publication
Interactioni
Subunit structurei
Monomer.
2 PublicationsStructurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8GTB6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 77 – 251 | FAD-binding PCMH-typePROSITE-ProRule annotationAdd BLAST | 175 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 232 – 235 | Poly-Gly | 4 |
Sequence similaritiesi
Belongs to the oxygen-dependent FAD-linked oxidoreductase family.Curated
Keywords - Domaini
SignalPhylogenomic databases
KOi | K20501 |
Family and domain databases
Gene3Di | 3.30.43.10, 1 hit |
InterProi | View protein in InterPro IPR012951 BBE IPR016166 FAD-bd_PCMH IPR036318 FAD-bd_PCMH-like_sf IPR016167 FAD-bd_PCMH_sub1 IPR006094 Oxid_FAD_bind_N |
Pfami | View protein in Pfam PF08031 BBE, 1 hit PF01565 FAD_binding_4, 1 hit |
SUPFAMi | SSF56176 SSF56176, 1 hit |
PROSITEi | View protein in PROSITE PS51387 FAD_PCMH, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q8GTB6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MNCSAFSFWF VCKIIFFFLS FHIQISIANP RENFLKCFSK HIPNNVANPK
60 70 80 90 100
LVYTQHDQLY MSILNSTIQN LRFISDTTPK PLVIVTPSNN SHIQATILCS
110 120 130 140 150
KKVGLQIRTR SGGHDAEGMS YISQVPFVVV DLRNMHSIKI DVHSQTAWVE
160 170 180 190 200
AGATLGEVYY WINEKNENLS FPGGYCPTVG VGGHFSGGGY GALMRNYGLA
210 220 230 240 250
ADNIIDAHLV NVDGKVLDRK SMGEDLFWAI RGGGGENFGI IAAWKIKLVA
260 270 280 290 300
VPSKSTIFSV KKNMEIHGLV KLFNKWQNIA YKYDKDLVLM THFITKNITD
310 320 330 340 350
NHGKNKTTVH GYFSSIFHGG VDSLVDLMNK SFPELGIKKT DCKEFSWIDT
360 370 380 390 400
TIFYSGVVNF NTANFKKEIL LDRSAGKKTA FSIKLDYVKK PIPETAMVKI
410 420 430 440 450
LEKLYEEDVG AGMYVLYPYG GIMEEISESA IPFPHRAGIM YELWYTASWE
460 470 480 490 500
KQEDNEKHIN WVRSVYNFTT PYVSQNPRLA YLNYRDLDLG KTNHASPNNY
510 520 530 540
TQARIWGEKY FGKNFNRLVK VKTKVDPNNF FRNEQSIPPL PPHHH
Polymorphismi
Several isoforms of the active tetrahydrocannabinolic acid synthase found in the 'drug-type' cannabis plants exist due to polymorphism.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 63 | I → L in strain: 001. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB057805 mRNA Translation: BAC41356.1 AB212829 Genomic DNA Translation: BAE48241.1 AB212832 Genomic DNA Translation: BAE48244.1 AB212834 Genomic DNA Translation: BAE48246.1 AB212835 Genomic DNA Translation: BAE48247.1 AB212837 Genomic DNA Translation: BAE48249.1 AB212838 Genomic DNA Translation: BAE48250.1 AB183698 Genomic DNA Translation: BAD82947.1 AB183699 Genomic DNA Translation: BAD82948.1 AB183700 Genomic DNA Translation: BAD82949.1 AB183701 Genomic DNA Translation: BAD82950.1 AB183702 Genomic DNA Translation: BAD82951.1 AB183703 Genomic DNA Translation: BAD82952.1 AB183704 Genomic DNA Translation: BAD82953.1 AB183705 Genomic DNA Translation: BAD82954.1 |
Genome annotation databases
KEGGi | ag:BAC41356 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB057805 mRNA Translation: BAC41356.1 AB212829 Genomic DNA Translation: BAE48241.1 AB212832 Genomic DNA Translation: BAE48244.1 AB212834 Genomic DNA Translation: BAE48246.1 AB212835 Genomic DNA Translation: BAE48247.1 AB212837 Genomic DNA Translation: BAE48249.1 AB212838 Genomic DNA Translation: BAE48250.1 AB183698 Genomic DNA Translation: BAD82947.1 AB183699 Genomic DNA Translation: BAD82948.1 AB183700 Genomic DNA Translation: BAD82949.1 AB183701 Genomic DNA Translation: BAD82950.1 AB183702 Genomic DNA Translation: BAD82951.1 AB183703 Genomic DNA Translation: BAD82952.1 AB183704 Genomic DNA Translation: BAD82953.1 AB183705 Genomic DNA Translation: BAD82954.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3VTE | X-ray | 2.75 | A | 28-545 | [»] | |
SMRi | Q8GTB6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Proteomic databases
PRIDEi | Q8GTB6 |
Genome annotation databases
KEGGi | ag:BAC41356 |
Phylogenomic databases
KOi | K20501 |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-12033 |
BRENDAi | 1.21.3.7 1159 |
Family and domain databases
Gene3Di | 3.30.43.10, 1 hit |
InterProi | View protein in InterPro IPR012951 BBE IPR016166 FAD-bd_PCMH IPR036318 FAD-bd_PCMH-like_sf IPR016167 FAD-bd_PCMH_sub1 IPR006094 Oxid_FAD_bind_N |
Pfami | View protein in Pfam PF08031 BBE, 1 hit PF01565 FAD_binding_4, 1 hit |
SUPFAMi | SSF56176 SSF56176, 1 hit |
PROSITEi | View protein in PROSITE PS51387 FAD_PCMH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | THCAS_CANSA | |
Accessioni | Q8GTB6Primary (citable) accession number: Q8GTB6 Secondary accession number(s): Q33DQ4, Q5NTX8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 6, 2013 |
Last sequence update: | March 1, 2003 | |
Last modified: | September 18, 2019 | |
This is version 69 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Plant Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references