Details for: OAZ3

Gene ID: 51686

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: OAZ3

Ensembl ID: ENSG00000143450

Description: ornithine decarboxylase antizyme 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural progenitor cell CL0011020
    CSI 2.76
    rCSI 12.13%
    PRS 99.28
  • GABAergic neuron CL0000617
    CSI 2.23
    rCSI 7.48%
    PRS 99.61

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Ornithine decarboxylase antizyme 3, encoded by the [OAZ3](/details-gene/51686) gene, is a protein-coding gene located on chromosome 1q21.3. It functions as a key negative regulator in polyamine metabolism, specifically through its ornithine decarboxylase inhibitor activity. Polyamines are essential for cell growth and proliferation, and their levels are tightly controlled. [OAZ3](/details-gene/51686) contributes to this regulation by binding to and targeting ornithine decarboxylase (ODC) for degradation. **Overall** expression data highlight its significant role in the nervous system, with high cell significance index (CSI) scores in [neural progenitor cell](/details-cell/CL0011020) and [GABAergic neuron](/details-cell/CL0000617). Research has also identified it as a spermatogenesis stage-specific antizyme, suggesting tissue-specific roles in both neural development and reproduction [Link](https://doi.org/10.1073/pnas.070055897). ## Cellular Roles and Expression Landscape The expression profile of [OAZ3](/details-gene/51686) suggests a specialized function within the central nervous system. **Overall**, it demonstrates a high CSI in both [neural progenitor cell](/details-cell/CL0011020) (CSI: 2.76) and mature [GABAergic neuron](/details-cell/CL0000617) (CSI: 2.23). This indicates that [OAZ3](/details-gene/51686) is not only a significant component of progenitor cells undergoing differentiation but also remains an important functional element in a specific subset of terminally differentiated neurons. Its role in regulating polyamine levels may be critical for both maintaining the progenitor state and supporting the metabolic demands of mature neuronal function. Beyond the nervous system, literature has established a distinct and critical role for [OAZ3](/details-gene/51686) in male reproduction. It was originally discovered as an antizyme specifically expressed in late-stage spermatids, indicating a crucial function in [spermatogenesis](/details-cell/GO:0007283) [Link](https://doi.org/10.1073/pnas.070055897). This highly tissue-specific expression pattern suggests that [OAZ3](/details-gene/51686) is regulated by distinct mechanisms in different cellular contexts, fulfilling specialized needs in both the brain and the testis. ## Pathways and Molecular Function [OAZ3](/details-gene/51686) is a central player in the regulation of polyamine biosynthesis, a fundamental metabolic process. Its primary molecular function is categorized as [ornithine decarboxylase inhibitor activity](/details-cell/GO:0008073), directly implicating it in the [Regulation of ornithine decarboxylase (odc)](https://reactome.org/content/detail/R-HSA-350562) pathway. By inhibiting ODC, the rate-limiting enzyme in polyamine synthesis, [OAZ3](/details-gene/51686) negatively regulates the [polyamine biosynthetic process](/details-cell/GO:0006596) and is also involved in the [negative regulation of polyamine transmembrane transport](/details-cell/GO:1902268). The functional annotations also connect [OAZ3](/details-gene/51686) to broader cellular processes such as the [positive regulation of protein catabolic process](/details-cell/GO:0045732), consistent with its role in targeting ODC for proteasomal degradation. Its presence in the [cytoplasm](/details-cell/GO:0005737), [cytosol](/details-cell/GO:0005829), and [nucleus](/details-cell/GO:0005634) suggests it can act on ODC in multiple cellular compartments. Furthermore, its annotation in [spermatogenesis](/details-cell/GO:0007283) aligns perfectly with its documented role in testicular germ cells. ## Research Directions The specific expression of [OAZ3](/details-gene/51686) in neural progenitors and GABAergic neurons, coupled with its known function as a negative regulator of cell growth via polyamine metabolism, opens several avenues for future investigation. ### Testable Hypotheses 1. **Hypothesis 1:** [OAZ3](/details-gene/51686) is a critical regulator of neurogenesis, where its expression must be precisely controlled to allow for initial progenitor proliferation (low [OAZ3](/details-gene/51686) activity) and subsequent terminal differentiation (high [OAZ3](/details-gene/51686) activity). Dysregulation of [OAZ3](/details-gene/51686) in [neural progenitor cell](/details-cell/CL0011020) could lead to neurodevelopmental disorders or tumorigenesis. 2. **Hypothesis 2:** In mature [GABAergic neuron](/details-cell/CL0000617), [OAZ3](/details-gene/51686) plays a neuroprotective role by preventing metabolic over-activity and excitotoxicity associated with excessive polyamine levels, which are known to modulate ion channels and neurotransmitter receptors. ### Key Experiments To test Hypothesis 1, a series of experiments using human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) could be performed. * **Approach:** Employ a CRISPR-Cas9 system to generate [OAZ3](/details-gene/51686) knockout and, separately, an inducible overexpression system in an NPC line. * **Assays:** Monitor cell proliferation rates via EdU incorporation assays. Induce neuronal differentiation and assess the efficiency and fate of differentiating cells using immunofluorescence for early (Tuj1) and mature (MAP2, GABA) neuronal markers, as well as progenitor markers (SOX2, Nestin). * **Analysis:** Perform RNA-sequencing at different time points during differentiation to identify downstream transcriptional changes and affected signaling pathways. Concurrently, measure intracellular polyamine levels using high-performance liquid chromatography (HPLC) to confirm the direct metabolic impact of [OAZ3](/details-gene/51686) manipulation. ### Therapeutic Potential As a negative regulator of ornithine decarboxylase, a well-established proto-oncogene, [OAZ3](/details-gene/51686) functions as a natural tumor suppressor. Its high expression in specific neural lineages suggests it may be particularly important in preventing cancers of the nervous system, such as glioblastoma, which often exhibit dysregulated polyamine metabolism. Therefore, [OAZ3](/details-gene/51686) itself is not a target for inhibition. Instead, therapeutic strategies could focus on **activation** or restoring its function. This could involve developing small molecules that stabilize the [OAZ3](/details-gene/51686) protein or enhance its binding to ODC, thereby promoting ODC degradation. Such an approach could represent a targeted therapy to reduce proliferation in tumors dependent on the polyamine synthesis pathway.

Genular Protein ID: 3391342917

Symbol: OAZ3_HUMAN

Name: Ornithine decarboxylase antizyme 3

UniProtKB Accession Codes:

Q9UMX2 E7EUE7 Q6GMR0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10781085

Title: Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: antizyme 3.

PubMed ID: 10781085

DOI: 10.1073/pnas.070055897

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17900240

Title: Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase.

PubMed ID: 17900240

DOI: 10.1042/bj20071004

Sequence Information:

  • Length: 235
  • Mass: 27413
  • Checksum: D9DA9CD9CAEED311
  • Sequence:
    • MPCKRCRPSV YSLSYIKRGK TRNYLYPIWS PYAYYLYCYK YRITLREKML PRCYKSITYK 
EEEDLTLQPR SCLQCSESLV GLQEGKSTEQ GNHDQLKELY SAGNLTVLAT DPLLHQDPVQ 
LDFHFRLTSQ TSAHWHGLLC DRRLFLDIPY QALDQGNRES LTATLEYVEE KTNVDSVFVN 
FQNDRNDRGA LLRAFSYMGF EVVRPDHPAL PPLDNVIFMV YPLERDVGHL PSEPP

Genular Protein ID: 2147237530

Symbol: A0A0G2JH29_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0G2JH29

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneTree 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 2 Pfam 1 Proteomes 2 RefSeq 1 SMR 1 SUPFAM 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

Sequence Information:

  • Length: 190
  • Mass: 21761
  • Checksum: E0B4F19A7A63CDE7
  • Sequence:
    • MTVPWRPGKR RITYKEEEDL TLQPRSCLQC SESLVGLQEG KSTEQGNHDQ LKELYSAGNL 
TVLATDPLLH QDPVQLDFHF RLTSQTSAHW HGLLCDRRLF LDIPYQALDQ GNRESLTATL 
EYVEEKTNVD SVFVNFQNDR NDRGALLRAF SYMGFEVVRP DHPALPPLDN VIFMVYPLER 
DVGHLPSEPP

Genular Protein ID: 1107520013

Symbol: H0Y7Y4_HUMAN

Name: N/A

UniProtKB Accession Codes:

H0Y7Y4

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneTree 1 HGNC 1 InterPro 3 MassIVE 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 2 Pfam 1 PhylomeDB 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 SMR 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

Sequence Information:

  • Length: 203
  • Mass: 23214
  • Checksum: 2EA8E00DD24B4F92
  • Sequence:
    • MRPEGGPRRR RQERPPPVLP AARRITYKEE EDLTLQPRSC LQCSESLVGL QEGKSTEQGN 
HDQLKELYSA GNLTVLATDP LLHQDPVQLD FHFRLTSQTS AHWHGLLCDR RLFLDIPYQA 
LDQGNRESLT ATLEYVEEKT NVDSVFVNFQ NDRNDRGALL RAFSYMGFEV VRPDHPALPP 
LDNVIFMVYP LERDVGHLPS EPP