OAZ1 ornithine decarboxylase antizyme 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: OAZ1provided by HGNC
Official Full Name: ornithine decarboxylase antizyme 1provided by HGNC
Primary source: HGNC:HGNC:8095
See related: Ensembl:ENSG00000104904 MIM:601579
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AZ1; AZI; OAZ
Summary: 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]
Expression: Ubiquitous expression in bone marrow (RPKM 404.8), lymph node (RPKM 286.9) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19p13.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	19	NC_000019.10 (2269486..2273488)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (2269520..2273487)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Data show the the interplay between the enzyme ornithine decarboxylase (ODC) and two regulatory proteins: antizyme (Az) and inhibitor (AzIN).
Title: Structural basis of antizyme-mediated regulation of polyamine homeostasis.
the effects of AZ on cell growth are independent of polyamines.
Title: Antizyme (AZ) regulates intestinal cell growth independent of polyamines.
Results show that ornithine decarboxylase antizyme 1 (OAZ1) simultaneously inhibits the proliferation and induces the differentiation of oral cancer cells.
Title: Effects of ornithine decarboxylase antizyme 1 on the proliferation and differentiation of human oral cancer cells.
To further understand its functions in CML pathogenesis, OAZ1 was overexpressed, and PCR array analysis was used to monitor the expression of key genes commonly involved in leukemia development.
Title: Assay of OAZ1 mRNA levels in chronic myeloid leukemia combined with application of leukemia PCR array identified relevant gene changes affected by antizyme.
Gene expression studies have identified altered expression of ornithine decarboxylase antizyme 1 in suicide completers with a history of mood disorders.
Title: Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide.
This study demomistrated that H3K4me3 modification plays an important role in up regulation of AOAZ1 in prefrontal cortex.
Title: Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide.
In the absence of amino acids, mTORC1 is inhibited, whereas mTORC2 is activated, leading to the inhibition of global protein synthesis and increased AZ1 synthesis via a cap-independent mechanism.
Title: Amino acids regulate expression of antizyme-1 to modulate ornithine decarboxylase activity.
AZ_95-176 is the minimal AZ peptide that is fully functioning in the binding of ODC and AZI and inhibition of their function.
Title: Minimal antizyme peptide fully functioning in the binding and inhibition of ornithine decarboxylase and antizyme inhibitor.
the differences in residues 125 and 140 in ODC and AZI are responsible for the differential antizyme-binding affinities
Title: Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor.
Data show that OAZ promotes the removal of Mps1 from centrosomes, and centrosome overproduction caused by reducing OAZ activity requires Mps1.
Title: Antizyme restrains centrosome amplification by regulating the accumulation of Mps1 at centrosomes.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Aurora A signaling, organism-specific biosystem (from Pathway Interaction Database)
Aurora A signaling, organism-specific biosystem
Aurora A signaling
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
Metabolism of polyamines, organism-specific biosystem (from REACTOME)
Metabolism of polyamines, organism-specific biosystemPolyamines is a family of molecules (i.e. putrescine, spermine, spermidine) derived from ornithine according to a decarboxylation/condensative process. More recently, it has been demonstrated that ar...
Nucleotide Metabolism, organism-specific biosystem (from WikiPathways)
Nucleotide Metabolism, organism-specific biosystemThe pathway outlined above focuses on purine metabolism and in particular that of guanine metabolism.
Regulation of ornithine decarboxylase (ODC), organism-specific biosystem (from REACTOME)
Regulation of ornithine decarboxylase (ODC), organism-specific biosystemPolyamines increase the production of antizyme (AZ). The carboxy-terminal half of antizyme interacts with ODC, generating an inactive AZ:ODC heterodimer complex. A carboxy-terminal domain of ODC is ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:495122

RH71137 (e-PCR)
- UniSTS:53041

OAZ1 (e-PCR)
- UniSTS:278862

D19S850 (e-PCR)
- UniSTS:154197

Homology

Homologs of the OAZ1 gene: The OAZ1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 242 organisms have orthologs with human gene OAZ1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ornithine decarboxylase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
ornithine decarboxylase inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
negative regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
negative regulation of polyamine transmembrane transport	IEA Inferred from Electronic Annotation more info
polyamine biosynthetic process	IEA Inferred from Electronic Annotation more info
positive regulation of intracellular protein transport	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
regulation of cellular amino acid metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ornithine decarboxylase antizyme 1

Names: ODC-Az; antizyme 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001301020.1 → NP_001287949.1 ornithine decarboxylase antizyme 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate, in-frame acceptor splice site at the second exon compared to variant 1. The resulting isoform (2) lacks 2 internal amino acids compared to isoform 1.

Source sequence(s)

BC100291, BM423450, HY050868

Consensus CDS

CCDS77214.1

UniProtKB/TrEMBL

J3QQY4

Related

ENSP00000463955.3, ENST00000582888.8

Conserved Domains (1) summary

pfam02100
Location:136 → 215

ODC_AZ; Ornithine decarboxylase antizyme
NM_004152.3 → NP_004143.1 ornithine decarboxylase antizyme 1 isoform 1

See identical proteins and their annotated locations for NP_004143.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC100291, HY050868

Consensus CDS

CCDS58639.1

UniProtKB/Swiss-Prot

P54368

Related

ENSP00000473381.1, ENST00000602676.6

Conserved Domains (1) summary

pfam02100
Location:138 → 217

ODC_AZ; Ornithine decarboxylase antizyme