Azin2 antizyme inhibitor 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Azin2provided by MGI
Official Full Name: antizyme inhibitor 2provided by MGI
Primary source: MGI:MGI:2442093
See related: Ensembl:ENSMUSG00000028789 AllianceGenome:MGI:2442093
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Adc; Azi2; Odcp; ODC-p; B930082O19; 4933429I20Rik
Summary: 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 2, the second member of this gene family. Like antizyme inhibitor 1, antizyme inhibitor 2 interacts with all 3 antizymes and stimulates ODC activity and polyamine uptake. However, unlike antizyme inhibitor 1, which is ubiquitously expressed and localized in the nucleus and cytoplasm, antizyme inhibitor 2 is predominantly expressed in the brain and testis and localized in the endoplasmic reticulum-golgi intermediate compartment. Recent studies indicate that antizyme inhibitor 2 is also expressed in specific cell types in ovaries, adrenal glands and pancreas, and in mast cells. The exact function of this gene is not known, however, available data suggest its role in cell growth, spermiogenesis, vesicular trafficking and secretion. There has been confusion in literature and databases over the nomenclature of this gene, stemming from an earlier report that a human cDNA clone (identical to ODCp/AZIN2) had arginine decarboxylase (ADC) activity (PMID:14738999). Subsequent studies in human and mouse showed that antizyme inhibitor 2 was devoid of arginine decarboxylase activity (PMID:19956990). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
Expression: Biased expression in testis adult (RPKM 55.5), lung adult (RPKM 9.7) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 D2.2; 4 62.48 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (128824026..128856250, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (128930233..128962456, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity.
Title: Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity.
Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology.
Title: Aberrant AZIN2 and polyamine metabolism precipitates tau neuropathology.
Testis of mice with different alterations in spermatogenesis and fertility, induced either genetically or pharmacologically, showed that both AZIN2 and OAZ3 are mainly expressed in the haploid germinal cells. AZIN2 was detected in spermatids and spermatozoa, as well as in Leydig cells, and in epithelial epidydimal cells.
Title: New insights of polyamine metabolism in testicular physiology: A role of ornithine decarboxylase antizyme inhibitor 2 (AZIN2) in the modulation of testosterone levels and sperm motility.
show, for the first time, an element of polyamine metabolism -AZIN2-, so far described as exclusively devoted to the control of polyamine concentrations, involved in regulating the biosynthesis and content of other amines like serotonin and histamine.
Title: A novel role for antizyme inhibitor 2 as a regulator of serotonin and histamine biosynthesis and content in mouse mast cells.
in contrast to human ODCp, mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity
Title: Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity.
AZIN2 may have a role in the modulation of reproductory and secretory functions.
Title: Antizyme inhibitor 2 hypomorphic mice. New patterns of expression in pancreas and adrenal glands suggest a role in secretory processes.
expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells
Title: Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells.
Both endogenous and FLAG-tagged AZIN2 localize to post-Golgi vesicles of the secretory pathway. Immuno-electron microscopy revealed that the vesicles associate mainly with the trans-Golgi network.
Title: Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking.
AZIN2 expression appears to be restricted to brain and testis and it is a labile protein degraded by a ubiquitin-dependent mechanism.
Title: Antizyme inhibitor 2: molecular, cellular and physiological aspects.
granule subtype-specific expression and its induction after MC activation suggest a role for AZIN2 as a local, in situ regulator of polyamine biosynthesis in association with serotonin-containing granules of mast cells
Title: Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Endonuclease-mediated (2)

General gene information

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Markers

Adc (e-PCR), detects polymorphism
- UniSTS:531464

BB398156 (e-PCR)
- UniSTS:207684

Adc (e-PCR), detects polymorphism
- UniSTS:546630

D4Mit72 (e-PCR), detects polymorphism
- UniSTS:130190

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
NOT enables arginine decarboxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables ornithine decarboxylase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables ornithine decarboxylase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables ornithine decarboxylase activator activity	IGI Inferred from Genetic Interaction more info	PubMed
enables ornithine decarboxylase activator activity	ISO Inferred from Sequence Orthology more info
NOT enables ornithine decarboxylase activity	IBA Inferred from Biological aspect of Ancestor more info
NOT enables ornithine decarboxylase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of protein catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within ornithine metabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within polyamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in polyamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of catalytic activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of polyamine transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of polyamine transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in putrescine biosynthetic process from ornithine	IBA Inferred from Biological aspect of Ancestor more info
involved_in trans-Golgi network membrane organization	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in cis-Golgi network	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum-Golgi intermediate compartment membrane	IDA Inferred from Direct Assay more info	PubMed
located_in granular vesicle	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
NOT located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in trans-Golgi network	ISO Inferred from Sequence Orthology more info
located_in transport vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: antizyme inhibitor 2

Names: ODC antizyme inhibitor-2; ODC-like protein; arginine decarboxylase; ornithine decarboxylase paralog; ornithine decarboxylase-like protein

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_001301841.1 → NP_001288770.1 antizyme inhibitor 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two consecutive exons in the 5' coding region (which results in translation initiation from an in-frame downstream AUG) and contains a novel 3' terminal exon compared to variant 1. The resulting isoform (2) is shorter with a distinct C-terminus compared to isoform 1.

Source sequence(s)

BC065772, CJ183131

Consensus CDS

CCDS80159.1

UniProtKB/TrEMBL

A8Y5E7

Related

ENSMUSP00000114086.2, ENSMUST00000119354.8

Conserved Domains (1) summary

cd00622
Location:1 → 312

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase
NM_172875.4 → NP_766463.1 antizyme inhibitor 2 isoform 1

See identical proteins and their annotated locations for NP_766463.1

Status: REVIEWED

Description

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

Source sequence(s)

AK077201, AL607086, BB398156, CJ183131

Consensus CDS

CCDS18678.1

UniProtKB/Swiss-Prot

A2A823, Q8BVM4

UniProtKB/TrEMBL

B2RSR5

Related

ENSMUSP00000030581.4, ENSMUST00000030581.10

Conserved Domains (1) summary

cd00622
Location:40 → 407

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000070.7 Reference GRCm39 C57BL/6J

Range

128824026..128856250 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006503106.5 → XP_006503169.1 antizyme inhibitor 2 isoform X1

Conserved Domains (1) summary

cd00622
Location:33 → 349

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase
XM_011240538.4 → XP_011238840.1 antizyme inhibitor 2 isoform X4

Conserved Domains (1) summary

cd00622
Location:1 → 312

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase
XM_006503108.5 → XP_006503171.1 antizyme inhibitor 2 isoform X3

Conserved Domains (1) summary

cd00622
Location:4 → 318

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase
XM_006503107.4 → XP_006503170.1 antizyme inhibitor 2 isoform X2

Conserved Domains (1) summary

cd00622
Location:40 → 350

PLPDE_III_ODC; Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Ornithine Decarboxylase