Tbio AZIN1 Antizyme inhibitor 1

Protein Summary

Description

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 (PubMed:17900240, PubMed:26305948). 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 (PubMed:17900240). 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. RNA editing of this gene, predominantly in the liver tissue, has been linked to the progression of hepatocellular carcinoma. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2014]

Uniprot Accession IDs

• O14977
• A6NCD5
• Q6IBQ7
• Q96D20
• AZI

Gene Name

• AZIN1

Ensembl ID

• ENST00000337198
• ENSP00000337180
• ENSG00000155096
• ENST00000347770
• ENSP00000321507

Symbol

• OAZI
• OAZIN
• AZI
• AZI1
• OAZI
• AZIA1
• OAZIN
• ODC1L

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.97
protein domain	0.92
transcription factor perturbation	0.84
disease perturbation	0.79
kinase perturbation	0.71

Protein Classes

PANTHER Classes

Protein / Lyase / Decarboxylase / Antizyme Inhibitor 1

DTO Classes

Protein / Enzyme / Lyase / Decarboxylase / Antizyme Inhibitor 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: 35.18   (req: < 5)

Gene RIFs: 11   (req: <= 3)

Antibodies: 153   (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: 35.18   (req: >= 5)

Gene RIFs: 11   (req: > 3)

Antibodies: 153   (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

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (81)

Explore Interacting Targets

1 – 10 of 81

• See Interactions on String-DB

OAZ3

Tbio

Family:  Enzyme

Novelty:  0.02374168

p_int:  1

Score:  0.989

Data Source:  BioPlex,Reactome,STRINGDB

OAZ1

Tbio

Family:  Enzyme

Novelty:  0.0224953

p_int:  0.999999026

p_ni:  9.4e-7

p_wrong:  3.4e-8

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

KLC4

Tdark

Novelty:  0.32552746

p_int:  0.999779462

p_ni:  0.000220534

p_wrong:  4e-9

Score:  0.568

Data Source:  BioPlex,STRINGDB

OAZ2

Tbio

Family:  Enzyme

Novelty:  0.1687351

p_int:  0.999570924

p_ni:  9.9e-8

p_wrong:  0.000428977

Score:  0.992

Data Source:  BioPlex,Reactome,STRINGDB

KLC2

Tbio

Novelty:  0.06284367

p_int:  0.999323795

p_ni:  0.000676205

Score:  0.739

Data Source:  BioPlex,STRINGDB

KLC1

Tbio

Novelty:  0.00653484

p_int:  0.993605183

p_ni:  0.006394817

Score:  0.823

Data Source:  BioPlex,STRINGDB

TDP2

Tchem

Family:  Enzyme

Novelty:  0.01104303

p_int:  0.990138778

p_ni:  0.009834175

p_wrong:  0.000027046

Score:  0.316

Data Source:  BioPlex,STRINGDB

KIF5B

Tbio

Novelty:  0.00515256

p_int:  0.946192793

p_ni:  0.053807207

Score:  0.679

Data Source:  BioPlex,STRINGDB

KIF5C

Tbio

Novelty:  0.0238573

p_int:  0.812226671

p_ni:  0.187773329

Score:  0.719

Data Source:  BioPlex,STRINGDB

ODC1

Tclin

Family:  Enzyme

Novelty:  0.00037968

Score:  0.909

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (6)

Reactome (4)

PathwayCommons (1)

WikiPathways (1)

Metabolism (R-HSA-1430728)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Reactome	Metabolism of polyamines	60 targets	R-HSA-351202
Reactome	Regulation of ornithine decarboxylase (ODC)	52 targets	R-HSA-350562

Name	Explore in Pharos	Explore in Source
Metabolism	2112 targets	R-HSA-1430728
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Metabolism of polyamines	60 targets	R-HSA-351202
Regulation of ornithine decarboxylase (ODC)	52 targets	R-HSA-350562

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (9)

Functions (2)

Components (3)

Processes (4)

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GO Term	Evidence	Assigned by
ornithine decarboxylase activator activity	Inferred from Direct Assay (IDA)	UniProtKB
ornithine decarboxylase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations (null)

No disease associations found

GWAS Traits (19)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 19

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3	3	3		89.7
leukocyte count	EFO_0004308	2	2	2		84.5
high density lipoprotein cholesterol measurement	EFO_0004612	2	2	2		79.6
reticulocyte measurement	EFO_0010700	1	1	1		72.5
alkaline phosphatase measurement	EFO_0004533	2	2	1	6.3	62.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 19

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3		89.7
leukocyte count	EFO_0004308	2		84.5
high density lipoprotein cholesterol measurement	EFO_0004612	2		79.6
reticulocyte measurement	EFO_0010700	1		72.5
alkaline phosphatase measurement	EFO_0004533	1	6.3	62.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Complete proteome
Nucleus
Polyamine biosynthesis
Reference proteome
Ubl conjugation

GWAS Trait Find Similar Targets

No Header	No Header
Agents acting on the renin-angiotensin system use measurement
alkaline phosphatase measurement
apolipoprotein A 1 measurement
diastolic blood pressure
granulocyte count
high density lipoprotein cholesterol measurement
leukocyte count
lymphocyte percentage of leukocytes
mean corpuscular volume
mean platelet volume

MGI Phenotype Find Similar Targets

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growth/size/body region phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	antizyme inhibitor 1	VGNC:916	464324
Macaque	antizyme inhibitor 1		693581
Mouse	antizyme inhibitor 1	MGI:1859169	54375
Rat	antizyme inhibitor 1	RGD:61934	58961
Dog	antizyme inhibitor 1	VGNC:38329	475058

Species	Name	OMA	EggNOG	Inparanoid
Chimp	antizyme inhibitor 1
Macaque	antizyme inhibitor 1
Mouse	antizyme inhibitor 1
Rat	antizyme inhibitor 1
Dog	antizyme inhibitor 1

Publication Statistics

PubMed Score 35.18

PubMed score by year

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PubTator Score 29.22

PubTator score by year

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Related Publications

Text Mined References (29)

GeneRif Annotations (11)

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PMID	Year	Title