Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding. Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production.
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The protein encoded by this gene belongs to the antizyme inhibitor family, which plays a role in cell growth and proliferation by maintaining polyamine homeostasis within the cell. Antizyme inhibitors are homologs of ornithine decarboxylase (ODC, the key enzyme in polyamine biosynthesis) that have lost the ability to decarboxylase ornithine; however, retain the ability to bind to antizymes. Antizymes negatively regulate intracellular polyamine levels by binding to ODC and targeting it for degradation, as well as by inhibiting polyamine uptake. Antizyme inhibitors function as positive regulators of polyamine levels by sequestering antizymes and neutralizing their effect. This gene encodes antizyme inhibitor 1, the first member of this gene family that is ubiquitously expressed, and is localized in the nucleus and cytoplasm. Overexpression of antizyme inhibitor 1 gene has been associated with increased proliferation, cellular transformation and tumorigenesis. Gene knockout studies showed that homozygous mutant mice lacking functional antizyme inhibitor 1 gene died at birth with abnormal liver morphology. [provided by RefSeq, Sep 2014]
ADC: Decarboxylates L-arginine to agmatine. Truncated splice isoforms probably lack activity. Belongs to the Orn/Lys/Arg decarboxylase class-II family. 5 isoforms of the human protein are produced by alternative splicing.
Protein type: Amino Acid Metabolism - arginine and proline; EC 18.104.22.168; Lyase; Mitochondrial
Chromosomal Location of Human Ortholog: 1p35.1
Cellular Component: axon; cis-Golgi network; cytoplasmic vesicle; cytosol; dendrite; ER-Golgi intermediate compartment membrane; nucleus; perikaryon; perinuclear region of cytoplasm; trans-Golgi network; transport vesicle
Molecular Function: arginine decarboxylase activity; ornithine decarboxylase activator activity; protein binding; putrescine transmembrane transporter activity
Biological Process: negative regulation of protein catabolic process; positive regulation of catalytic activity; putrescine biosynthetic process from ornithine; putrescine transport