N‐terminal cysteine oxidases (NCOs) use molecular oxygen to oxidise the amino‐
terminal cysteine of specific proteins, thereby initiating the proteolytic N‐degron
pathway. To expand the characterisation of the plant family of NCOs (plant cysteine
oxidases [PCOs]), we performed a phylogenetic analysis across different taxa in
terms of sequence similarity and transcriptional regulation. Based on this survey, we
propose a distinction of PCOs into two main groups. A‐type PCOs are conserved
across all plant species and are generally unaffected at the messenger RNA level by
oxygen availability. Instead, B‐type PCOs appeared in spermatophytes to acquire
transcriptional regulation in response to hypoxia. The inactivation of two A‐type
PCOs in Arabidopsis thaliana, PCO4 and PCO5, is sufficient to activate the anaerobic
response in young seedlings, whereas the additional removal of B‐type PCOs leads
to a stronger induction of anaerobic genes and impairs plant growth and
development. Our results show that both PCO types are required to regulate the
anaerobic response in angiosperms. Therefore, while it is possible to distinguish two
clades within the PCO family, we conclude that they all contribute to restrain the
anaerobic transcriptional programme in normoxic conditions and together generate
a molecular switch to toggle the hypoxic response