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SMOX spermine oxidase [ Homo sapiens (human) ]

Gene ID: 54498, updated on 11-Apr-2024

Summary

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Official Symbol
SMOXprovided by HGNC
Official Full Name
spermine oxidaseprovided by HGNC
Primary source
HGNC:HGNC:15862
See related
Ensembl:ENSG00000088826 MIM:615854; AllianceGenome:HGNC:15862
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
PAO; SMO; PAO1; PAOH; PAO-1; PAOH1; C20orf16
Summary
Polyamines are ubiquitous polycationic alkylamines which include spermine, spermidine, putrescine, and agmatine. These molecules participate in a broad range of cellular functions which include cell cycle modulation, scavenging reactive oxygen species, and the control of gene expression. These molecules also play important roles in neurotransmission through their regulation of cell-surface receptor activity, involvement in intracellular signalling pathways, and their putative roles as neurotransmitters. This gene encodes an FAD-containing enzyme that catalyzes the oxidation of spermine to spermadine and secondarily produces hydrogen peroxide. Multiple transcript variants encoding different isoenzymes have been identified for this gene, some of which have failed to demonstrate significant oxidase activity on natural polyamine substrates. The characterized isoenzymes have distinctive biochemical characteristics and substrate specificities, suggesting the existence of additional levels of complexity in polyamine catabolism. [provided by RefSeq, Jul 2012]
Expression
Ubiquitous expression in brain (RPKM 15.8), bone marrow (RPKM 10.0) and 25 other tissues See more
Orthologs
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Genomic context

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See SMOX in Genome Data Viewer
Location:
20p13
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (4148828..4187727)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (4183413..4222031)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (4129475..4168374)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4014121-4014765 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17491 Neighboring gene ferritin light chain pseudogene 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:4026722-4027222 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:4027223-4027723 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4043892-4044780 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:4052097-4052598 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:4052599-4053098 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr20:4055096-4056295 Neighboring gene ribosomal protein L21 pseudogene 2 Neighboring gene CRISPRi-validated cis-regulatory element chr20.311 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4089506-4090058 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4090059-4090610 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4090944-4091508 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr20:4115669-4116868 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4129207-4130148 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4130149-4131090 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12638 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60212 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:4138284-4138784 Neighboring gene uncharacterized LOC124904861 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4141411-4142344 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4148169-4148870 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12639 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12640 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12641 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:4175883-4176064 Neighboring gene MPRA-validated peak4129 silencer Neighboring gene long intergenic non-protein coding RNA 1433 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:4197441-4198178 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17493 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:4202467-4202967 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:4212957-4213457 Neighboring gene adrenoceptor alpha 1D Neighboring gene Sharpr-MPRA regulatory region 5115

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study. Fadista J, et al. Sci Rep, 2021 Aug 31. PMID 34465810, Free PMC Article
  2. Spectroscopic and calorimetric characterization of spermine oxidase and its association forms. Leonetti A, et al. Biochem J, 2017 Dec 14. PMID 29138259
  3. Epigenetic silencing of miR-124 prevents spermine oxidase regulation: implications for Helicobacter pylori-induced gastric cancer. Murray-Stewart T, et al. Oncogene, 2016 Oct 20. PMID 27041578, Free PMC Article
  4. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase. Chaturvedi R, et al. Oncogene, 2015 Jun. PMID 25174398, Free PMC Article
  5. Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm. Cervelli M, et al. BMC Cancer, 2010 Oct 14. PMID 20946629, Free PMC Article

See all (45) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Protective Role of Spermidine in Colitis and Colon Carcinogenesis.
    Title: Protective Role of Spermidine in Colitis and Colon Carcinogenesis.
  2. Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study.
    Title: Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study.
  3. SMOX plays a central role in the formation of bile canalicular lumen in liver cells by activating Akt pathway through acrolein production.
    Title: Spermine oxidase promotes bile canalicular lumen formation through acrolein production.
  4. Data suggest that intermolecular disulfide bond links spermine oxidase (SMOX) molecules to form the homodimer and plays a critical role in the stabilization of the overall three-dimensional SMOX structure.
    Title: Spectroscopic and calorimetric characterization of spermine oxidase and its association forms.
  5. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.
    Title: Epigenetic silencing of miR-124 prevents spermine oxidase regulation: implications for Helicobacter pylori-induced gastric cancer.
  6. effect of Tat on Nrf2 activation in human neuroblastoma cells and the role of NMDA receptor and spermine oxidase on Tat-induced nuclear factor erythroid 2-related factor 2 (Nrf2) activation
    Title: HIV-Tat Induces the Nrf2/ARE Pathway through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells.
  7. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine, and increases gastric cancer risk.
    Title: Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase.
  8. study postulates a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs.
    Title: Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.
  9. Tat was found to induce reactive oxygen species production and to affect cell viability in SH-SY5Y cells, these effects being mediated by spermine oxidase (SMO)
    Title: A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity.
  10. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA.
    Title: Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA.
Submit: New GeneRIF Correction See all GeneRIFs (22)

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

EBI GWAS Catalog

Description
Genome-wide association study of panic disorder in the Japanese population.
EBI GWAS Catalog
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat-induced activation of spermine oxidase (SMO) activity involves NMDAR stimulation in human neuroblastoma PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC1010, FLJ20746

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables N1-acetylspermine:oxygen oxidoreductase (N1-acetylspermidine-forming) activity IEA
Inferred from Electronic Annotation
more info
  
enables norspermine:oxygen oxidoreductase activity IEA
Inferred from Electronic Annotation
more info
  
enables polyamine oxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables polyamine oxidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables spermine:oxygen oxidoreductase (spermidine-forming) activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in polyamine biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in polyamine catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in spermine catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in spermine catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in xenobiotic metabolic process TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in nuclear membrane IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
spermine oxidase
Names
flavin containing amine oxidase
flavin-containing spermine oxidase
polyamine oxidase 1
putative cyclin G1 interacting protein
NP_001257620.1
NP_787033.1
NP_787034.1
NP_787035.1
NP_787036.1
XP_011527563.1
XP_047296173.1
XP_047296174.1
XP_047296175.1
XP_047296176.1
XP_047296177.1
XP_047296178.1
XP_047296179.1
XP_054179519.1
XP_054179520.1
XP_054179521.1
XP_054179522.1
XP_054179523.1
XP_054179524.1
XP_054179525.1
XP_054179526.1

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)

  1. NM_001270691.2 → NP_001257620.1  spermine oxidase isoform 6

    See identical proteins and their annotated locations for NP_001257620.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) has an additional in-frame segment of the coding region, compared to variant 1. It encodes a longer isoform (6), also known as SMOX5 or SMO5, that has an additional internal segment compared to isoform 1.
    Source sequence(s)
    AW136764, AY358104, BG679874, EF032141
    Consensus CDS
    CCDS74702.1
    UniProtKB/TrEMBL
    B4DE63
    Related
    ENSP00000478305.1, ENST00000621355.4
    Conserved Domains (2) summary
    PLN02568
    Location:50 → 578
    PLN02568; polyamine oxidase
    pfam13450
    Location:45 → 88
    NAD_binding_8; NAD(P)-binding Rossmann-like domain

  2. NM_175839.3 → NP_787033.1  spermine oxidase isoform 1

    See identical proteins and their annotated locations for NP_787033.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the most abundant transcript and encodes isoform (1), also known as PAOh1.
    Source sequence(s)
    AW136764, AY358104, BG679874, EF032141
    Consensus CDS
    CCDS13075.1
    UniProtKB/Swiss-Prot
    A2A2P5, A2A2P6, A8BE87, D3DVZ4, Q5TE26, Q5TE27, Q6UY28, Q8IX00, Q96LC3, Q96LC4, Q96QT3, Q9BW38, Q9H6H1, Q9NP51, Q9NPY1, Q9NPY2, Q9NWM0
    UniProtKB/TrEMBL
    B4DE63
    Related
    ENSP00000307252.4, ENST00000305958.9
    Conserved Domains (2) summary
    PLN02568
    Location:50 → 548
    PLN02568; polyamine oxidase
    pfam13450
    Location:45 → 88
    NAD_binding_8; NAD(P)-binding Rossmann-like domain

  3. NM_175840.3 → NP_787034.1  spermine oxidase isoform 2

    See identical proteins and their annotated locations for NP_787034.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (2), also known as PAOh2, that is missing an internal segment compared to isoform 1.
    Source sequence(s)
    AW136764, AY358104, BG679874, EF032141
    Consensus CDS
    CCDS13076.1
    UniProtKB/TrEMBL
    B4DE63
    Related
    ENSP00000344595.6, ENST00000339123.10
    Conserved Domains (1) summary
    cl27535
    Location:50 → 495
    Amino_oxidase; Flavin containing amine oxidoreductase

  4. NM_175841.3 → NP_787035.1  spermine oxidase isoform 3

    See identical proteins and their annotated locations for NP_787035.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (3), also known as PAOh3, that is missing an internal segment compared to isoform 1.
    Source sequence(s)
    AW136764, AY033891, BG679874
    Consensus CDS
    CCDS13077.1
    UniProtKB/Swiss-Prot
    Q9NWM0
    Related
    ENSP00000341775.2, ENST00000346595.6
    Conserved Domains (1) summary
    cl27535
    Location:146 → 183
    Amino_oxidase; Flavin containing amine oxidoreductase

  5. NM_175842.3 → NP_787036.1  spermine oxidase isoform 4

    See identical proteins and their annotated locations for NP_787036.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has multiple differences in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 4, also known as PAOh4, which is shorter than isoform 1.
    Source sequence(s)
    AW136764, AY358104, BG679874, EF032141
    Consensus CDS
    CCDS13078.1
    UniProtKB/TrEMBL
    B4DE63
    Related
    ENSP00000278795.3, ENST00000278795.7
    Conserved Domains (1) summary
    cl27535
    Location:50 → 525
    Amino_oxidase; Flavin containing amine oxidoreductase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    4148828..4187727
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047440218.1 → XP_047296174.1  spermine oxidase isoform X1

  2. XM_047440222.1 → XP_047296178.1  spermine oxidase isoform X3

  3. XM_011529261.3 → XP_011527563.1  spermine oxidase isoform X1

    See identical proteins and their annotated locations for XP_011527563.1

    UniProtKB/TrEMBL
    B4DE63
    Conserved Domains (2) summary
    PLN02568
    Location:50 → 578
    PLN02568; polyamine oxidase
    pfam13450
    Location:45 → 88
    NAD_binding_8; NAD(P)-binding Rossmann-like domain

  4. XM_047440220.1 → XP_047296176.1  spermine oxidase isoform X2

    UniProtKB/Swiss-Prot
    A2A2P5, A2A2P6, A8BE87, D3DVZ4, Q5TE26, Q5TE27, Q6UY28, Q8IX00, Q96LC3, Q96LC4, Q96QT3, Q9BW38, Q9H6H1, Q9NP51, Q9NPY1, Q9NPY2, Q9NWM0
    Related
    ENSP00000368773.2, ENST00000379460.6

  5. XM_047440223.1 → XP_047296179.1  spermine oxidase isoform X3

  6. XM_047440217.1 → XP_047296173.1  spermine oxidase isoform X1

  7. XM_047440219.1 → XP_047296175.1  spermine oxidase isoform X1

  8. XM_047440221.1 → XP_047296177.1  spermine oxidase isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    4183413..4222031
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054323545.1 → XP_054179520.1  spermine oxidase isoform X1

  2. XM_054323550.1 → XP_054179525.1  spermine oxidase isoform X3

  3. XM_054323546.1 → XP_054179521.1  spermine oxidase isoform X1

  4. XM_054323548.1 → XP_054179523.1  spermine oxidase isoform X2

    UniProtKB/Swiss-Prot
    A2A2P5, A2A2P6, A8BE87, D3DVZ4, Q5TE26, Q5TE27, Q6UY28, Q8IX00, Q96LC3, Q96LC4, Q96QT3, Q9BW38, Q9H6H1, Q9NP51, Q9NPY1, Q9NPY2, Q9NWM0

  5. XM_054323551.1 → XP_054179526.1  spermine oxidase isoform X3

  6. XM_054323544.1 → XP_054179519.1  spermine oxidase isoform X1

  7. XM_054323547.1 → XP_054179522.1  spermine oxidase isoform X1

  8. XM_054323549.1 → XP_054179524.1  spermine oxidase isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_019025.2: Suppressed sequence

    Description
    NM_019025.2: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NWM0.1 GenPept UniProtKB/Swiss-Prot:Q9NWM0

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