Ethylene signaling (ETR/ERS receptor-CTR1-EIN2-EBF-EIN3/EIL1 module)

Ethylene signaling in land plants is a double-negative relay from the endoplasmic reticulum to the nucleus. Ethylene is perceived by a family of ER-membrane receptors related to bacterial two-component histidine kinases (in Arabidopsis ETR1 and ERS1 of subfamily 1 and ETR2, ERS2 and EIN4 of subfamily 2), which bind the gas through a copper cofactor in their N-terminal transmembrane domain. In the absence of ethylene the receptors keep the associated Raf-like protein kinase CTR1 active; CTR1 phosphorylates the cytosolic C-terminal domain of the NRAMP-like ER membrane protein EIN2, preventing its signalling. Ethylene binding inactivates the receptors and CTR1, so EIN2 is dephosphorylated and proteolytically cleaved; the released C-terminal fragment (EIN2-CEND) moves to the nucleus and also binds the 3' UTRs of EBF1 and EBF2 mRNAs, repressing their translation in cytoplasmic P-bodies. EBF1 and EBF2 are F-box substrate adaptors of SCF E3 ubiquitin ligases that continuously target the transcription factors EIN3 and EIL1 for proteasomal degradation; their inhibition, together with ethylene-induced turnover of the EBF proteins, stabilizes EIN3/EIL1 in the nucleus. EIN3/EIL1 bind EIN3-binding sites in target promoters and activate the ethylene transcriptional cascade (e.g. ERF1), including EBF2 and receptor genes as negative feedback. Ethylene biosynthesis (ACC synthase and ACC oxidase), receptor-associated regulators such as RTE1, and downstream ERF-family transcription factors are outside this module.

Arabidopsis thaliana proteins are used as representative members; each is grounded with its reviewed UniProtKB accession taken from the gene review folders (ETR1 P49333, ERS1 Q38846, CTR1 Q05609, EIN2 Q9S814, EBF1 Q9SKK0, EBF2 Q708Y0, EIN3 O24606, EIL1 Q9SLH0); every grounded member has a completed gene review. Only ETR1 and ERS1 are listed for the receptor family; ETR2, ERS2 and EIN4 (subfamily 2) are functionally equivalent receptors not reviewed here. The receptor annoton uses ethylene receptor activity (GO:0038199), matching the ETR1 and ERS1 reviews; the in vitro histidine kinase activity of subfamily 1 is not modeled as the signalling output because ERS1 His autophosphorylation is lost when assayed in the presence of both Mg2+ and Mn2+ and kinase activity is largely dispensable for receptor output. EIN2 is modeled with two annotons, matching its review: an ER-localized signalling adaptor (GO:0035591, CTR1 target, cleaved to release EIN2-CEND) and an mRNA 3'-UTR binding activity (GO:0003730) of EIN2-CEND that represses EBF1/EBF2 translation in P-bodies. The EIN2 chromatin/histone acetylation role is noted in the EIN2 review but omitted here to keep the relay minimal. The protease that cleaves EIN2 is not established, so no annoton is asserted for it. The SCF core subunits (ASK1/ASK2, CUL1, RBX1) are shared with other SCF ligases and are described rather than modeled. No PANTHER family ids are asserted. No production GO-CAM in gocams/index.tsv contains these Arabidopsis proteins (checked 2026-10-06 by AGI locus and accession), so no gocam_associations are given.