THE plant hormone auxin has a central role in many aspects of plant growth and development1,2. By screening for mutants of Arabidopsis that are resistant to exogenous auxin, we have identified several genes that are required for normal auxin response3. One of these genes, AXR1, is defined by recessive mutations that confer auxin resistance to the roots, rosettes and inflorescences of mutant plants4-6. In addition, axr1 mutants display a variety of morphological defects that are consistent with a reduction in auxin sensitivity5. Here we isolate the AXR1 gene using a map-based approach and report that AXR1 encodes a new protein with significant sequence similarity to the ubiquitin-activating enzyme E1. The AXR1 protein is highly diverged from previously characterized E1 enzymes, however, and lacks a key cysteine residue that is essential for E1 activity7. AXR1 may therefore define a new class of enzymes in the ubiquitin pathway or it may have a novel function in cellular regulation which is unrelated to ubiquitin conjugation.