Tbio OAZ1 Ornithine decarboxylase antizyme 1

Protein Summary

Description

Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome (PubMed:17900240, PubMed:26305948, PubMed:26443277). Triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC (PubMed:26305948). Stabilizes AZIN2 by interfering with its ubiquitination (PubMed:17900240). Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol (PubMed:12097147). The protein encoded by this gene belongs to the ornithine decarboxylase antizyme family, which plays a role in cell growth and proliferation by regulating intracellular polyamine levels. Expression of antizymes requires +1 ribosomal frameshifting, which is enhanced by high levels of polyamines. Antizymes in turn bind to and inhibit ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis; thus, completing the auto-regulatory circuit. This gene encodes antizyme 1, the first member of the antizyme family, that has broad tissue distribution, and negatively regulates intracellular polyamine levels by binding to and targeting ODC for degradation, as well as inhibiting polyamine uptake. Antizyme 1 mRNA contains two potential in-frame AUGs; and studies in rat suggest that alternative use of the two translation initiation sites results in N-terminally distinct protein isoforms with different subcellular localization. Alternatively spliced transcript variants have also been noted for this gene. [provided by RefSeq, Dec 2014]

Uniprot Accession IDs

• P54368
• O43382
• Q14989
• Q92595
• Q9UPL9
• AZ1

Gene Name

• OAZ1

Ensembl ID

• ENST00000602676
• ENSP00000473381
• ENSG00000104904

Symbol

• OAZ
• AZ1
• AZI
• OAZ

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
disease perturbation	0.99
virus perturbation	0.88
transcription factor perturbation	0.84
transcription factor binding site profile	0.76

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Ornithine Decarboxylase Antizyme 1

DTO Classes

Protein / Enzyme Modulator / Ornithine Decarboxylase Antizyme 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 47.21   (req: < 5)

Gene RIFs: 23   (req: <= 3)

Antibodies: 105   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 47.21   (req: >= 5)

Gene RIFs: 23   (req: > 3)

Antibodies: 105   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 6

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0