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    SMOX spermine oxidase [ Homo sapiens (human) ]

    Gene ID: 54498, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (4148828..4187727)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (4183413..4222031)
    RS_2024_09 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. Oxidation of spermidine and spermine in rat liver: purification and properties of polyamine oxidase. Hölttä E. Biochemistry, 1977 Jan 11. PMID 12798
    3. Purification by affinity chromatography and characterization of porcine liver cytoplasmic polyamine oxidase. Tsukada T, et al. Int J Biochem, 1988. PMID 3181599
    4. Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure. Wang Y, et al. Cancer Res, 2001 Jul 15. PMID 11454677
    5. Cloning and characterization of multiple human polyamine oxidase splice variants that code for isoenzymes with different biochemical characteristics. Murray-Stewart T, et al. Biochem J, 2002 Dec 15. PMID 12398765, 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)

    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 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 oxidase 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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    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_2024_08

    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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

    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
      UniProtKB/TrEMBL
      B4DE63
      Related
      ENSP00000368773.2, ENST00000379460.6

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

    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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

    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
      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

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

      UniProtKB/TrEMBL
      B4DE63

    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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