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UniProt release 2013_02

Published February 6, 2013


The smoke's devils

The first written evidence of the therapeutic and psychoactive use of Cannabis is attributed to the legendary emperor of China Shen-nung who lived some 5,000 years ago. He stated in his famous herbal “Pen-ts’ao Ching” that “the fruits of hemp, if taken in excess will allow ‘seeing devils’. If taken over a long term, it makes one communicate with spirits and lightens one’s body” (in An archaeological and historical account of Cannabis in China). Until 1942, Cannabis was listed in the United States Pharmacopoeia and it was only in 1971 that most European countries banned Cannabis by adopting the Convention on Psychotropic Substances established by the United Nations.

Although marijuana has been used for centuries, the biological processes underlying its psychoactive effects have long remained a mystery. It is only recently that the cannabinoid biosynthetic pathway has been elucidated. The production of Cannabis’ major psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), starts with the condensation of hexanoyl-CoA with three molecules of malonyl-CoA to yield olivetolic acid (OA). It was postulated that a type III polyketide synthase was catalyzing this reaction, although all type III PKSs from Cannabis characterized so far were only able to produce byproducts instead of OA. A few months ago, it was shown that the inability of OLS/TKS, a cloned tetraketide synthase, to synthesize OA was due to the absence of an accessory protein, olivetolic acid cyclase. In the presence of olivetolic acid cyclase, OA is synthesized. It is then geranylated to form cannabigerolic acid, which is further converted by oxidocyclase enzymes to the major cannabinoids, delta-9-tetrahydrocannabinolic acid (THCA) in “drug-type” Cannabis and cannabidiolic acid (CBDA) in “fiber-type” Cannabis. THCA and CBDA are decarboxylated by a non-enzymatic reaction during storage or smoking to give rise to their chemically neutral forms, THC (the neurologically active substance) and CBD, respectively.

Thanks to the recent publication of the complete sequence of the genome of Cannabis sativa, most enzymes involved in the THC/CBD biosynthetic pathway have been identified and manually annotated in UniProtKB/Swiss-Prot.

UniProtKB news

Cross-references to mycoCLAP

Cross-references have been added to mycoCLAP, a database of fungal genes encoding lignocellulose-active proteins.

mycoCLAP is available at

The format of the explicit links in the flat file is:

Resource abbreviation mycoCLAP
Resource identifier mycoCLAP identifier
Example P55296:
DR   mycoCLAP; MAN26A_PIRSP; -.

Show all the entries having a cross-reference to mycoCLAP.

Changes to keywords

New keyword: Modified keywords:

Changes to the controlled vocabulary for PTMs

New terms for the feature key ‘Modified residue’ (‘MOD_RES’ in the flat file):
  • (3R)-3-hydroxyarginine
  • (3S)-3-hydroxyhistidine