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Protein

Spermine oxidase

Gene

SMOX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use N1-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal.

Catalytic activityi

Spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2.

Cofactori

FADBy similarityNote: Binds 1 FAD per subunit.By similarity

Enzyme regulationi

Inhibited at more than 90% by SL-11144, SL-11150 and SL-11158, at concentrations less than 1 µM.

Kineticsi

Kcat is 27-fold higher with spermine than N1-acetylspermine as substrate for isoform 1 and isoform 6.
  1. KM=0.6 µM for spermine (isoform 1)3 Publications
  2. KM=0.5 µM for spermine (isoform 6)3 Publications
  3. KM=3.0 µM for N1-acetylspermine (Isoform 1 and isoform 6)3 Publications

    pH dependencei

    Optimum pH is 9.5 with spermine as substrate.3 Publications

    Pathwayi: spermine degradation

    This protein is involved in the pathway spermine degradation, which is part of Amine and polyamine degradation.
    View all proteins of this organism that are known to be involved in the pathway spermine degradation and in Amine and polyamine degradation.

    GO - Molecular functioni

    GO - Biological processi

    • polyamine biosynthetic process Source: Reactome
    • polyamine catabolic process Source: UniProtKB
    • spermine catabolic process Source: UniProtKB

    Keywordsi

    Molecular functionOxidoreductase
    LigandFAD, Flavoprotein

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01609-MONOMER
    BRENDAi1.5.3.16 2681
    ReactomeiR-HSA-141334 PAOs oxidise polyamines to amines
    R-HSA-351200 Interconversion of polyamines
    SABIO-RKQ9NWM0
    UniPathwayiUPA00211

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Spermine oxidase (EC:1.5.3.16)
    Alternative name(s):
    Polyamine oxidase 1
    Short name:
    PAO-1
    Short name:
    PAOh1
    Gene namesi
    Name:SMOX
    Synonyms:C20orf16, SMO
    ORF Names:UNQ3039/PRO9854
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000088826.17
    HGNCiHGNC:15862 SMOX
    MIMi615854 gene
    neXtProtiNX_Q9NWM0

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi320C → R: No change in enzymatic activity. 1 Publication1

    Organism-specific databases

    DisGeNETi54498
    OpenTargetsiENSG00000088826
    PharmGKBiPA25701

    Chemistry databases

    ChEMBLiCHEMBL2176769
    DrugBankiDB00127 Spermine

    Polymorphism and mutation databases

    BioMutaiSMOX
    DMDMi50401688

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000998771 – 555Spermine oxidaseAdd BLAST555

    Proteomic databases

    MaxQBiQ9NWM0
    PaxDbiQ9NWM0
    PeptideAtlasiQ9NWM0
    PRIDEiQ9NWM0

    PTM databases

    iPTMnetiQ9NWM0
    PhosphoSitePlusiQ9NWM0

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed in human tumor cell lines. Isoform 4 is only found in an embryonal kidney cell line.1 Publication

    Inductioni

    By antitumor polyamine analogs.

    Gene expression databases

    BgeeiENSG00000088826
    CleanExiHS_SMO
    HS_SMOX
    ExpressionAtlasiQ9NWM0 baseline and differential
    GenevisibleiQ9NWM0 HS

    Organism-specific databases

    HPAiHPA047117
    HPA060198

    Interactioni

    Protein-protein interaction databases

    BioGridi119994, 8 interactors
    STRINGi9606.ENSP00000307252

    Chemistry databases

    BindingDBiQ9NWM0

    Structurei

    3D structure databases

    ProteinModelPortaliQ9NWM0
    SMRiQ9NWM0
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the flavin monoamine oxidase family.Curated

    Phylogenomic databases

    eggNOGiKOG0685 Eukaryota
    ENOG410XQW0 LUCA
    GeneTreeiENSGT00530000062888
    HOVERGENiHBG053499
    InParanoidiQ9NWM0
    KOiK12259
    OMAiHTHSSFY
    OrthoDBiEOG091G06OV
    PhylomeDBiQ9NWM0
    TreeFamiTF318348

    Family and domain databases

    Gene3Di3.50.50.60, 4 hits
    InterProiView protein in InterPro
    IPR002937 Amino_oxidase
    IPR036188 FAD/NAD-bd_sf
    PfamiView protein in Pfam
    PF01593 Amino_oxidase, 2 hits
    SUPFAMiSSF51905 SSF51905, 3 hits

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

    Note: The resultant proteins have different biochemical characteristics and substrate specificity.
    Isoform 1 (identifier: Q9NWM0-1) [UniParc]FASTAAdd to basket
    Also known as: PAOh1, SMO

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MQSCESSGDS ADDPLSRGLR RRGQPRVVVI GAGLAGLAAA KALLEQGFTD
    60 70 80 90 100
    VTVLEASSHI GGRVQSVKLG HATFELGATW IHGSHGNPIY HLAEANGLLE
    110 120 130 140 150
    ETTDGERSVG RISLYSKNGV ACYLTNHGRR IPKDVVEEFS DLYNEVYNLT
    160 170 180 190 200
    QEFFRHDKPV NAESQNSVGV FTREEVRNRI RNDPDDPEAT KRLKLAMIQQ
    210 220 230 240 250
    YLKVESCESS SHSMDEVSLS AFGEWTEIPG AHHIIPSGFM RVVELLAEGI
    260 270 280 290 300
    PAHVIQLGKP VRCIHWDQAS ARPRGPEIEP RGEGDHNHDT GEGGQGGEEP
    310 320 330 340 350
    RGGRWDEDEQ WSVVVECEDC ELIPADHVIV TVSLGVLKRQ YTSFFRPGLP
    360 370 380 390 400
    TEKVAAIHRL GIGTTDKIFL EFEEPFWGPE CNSLQFVWED EAESHTLTYP
    410 420 430 440 450
    PELWYRKICG FDVLYPPERY GHVLSGWICG EEALVMEKCD DEAVAEICTE
    460 470 480 490 500
    MLRQFTGNPN IPKPRRILRS AWGSNPYFRG SYSYTQVGSS GADVEKLAKP
    510 520 530 540 550
    LPYTESSKTA PMQVLFSGEA THRKYYSTTH GALLSGQREA ARLIEMYRDL

    FQQGT
    Note: Low affinity for acetylated polyamine.
    Length:555
    Mass (Da):61,819
    Last modified:October 1, 2000 - v1
    Checksum:iBDBEA65ECE9F45BF
    GO
    Isoform 2 (identifier: Q9NWM0-2) [UniParc]FASTAAdd to basket
    Also known as: PAOh2

    The sequence of this isoform differs from the canonical sequence as follows:
         282-334: Missing.

    Note: Low affinity for acetylated polyamine.
    Show »
    Length:502
    Mass (Da):56,091
    Checksum:i45921536D1B92403
    GO
    Isoform 3 (identifier: Q9NWM0-3) [UniParc]FASTAAdd to basket
    Also known as: PAOh3

    The sequence of this isoform differs from the canonical sequence as follows:
         146-510: Missing.

    Note: Major isoform. Has the highest affinity for the 3 substrates. Has a greater affinity for spermidine and spermine than for N1-acetylspermine.
    Show »
    Length:190
    Mass (Da):20,630
    Checksum:iC6A51E1B71E3A56A
    GO
    Isoform 4 (identifier: Q9NWM0-4) [UniParc]FASTAAdd to basket
    Also known as: PAOh4

    The sequence of this isoform differs from the canonical sequence as follows:
         282-334: Missing.
         510-510: A → AHGSSTKQQPGHLFSSKCPEQPLDANRGAVK

    Note: Has the lowest Km values for the different substrates and has the highest affinity for spermidine.
    Show »
    Length:532
    Mass (Da):59,279
    Checksum:iB9AE5FCB9B7762B3
    GO
    Isoform 5 (identifier: Q9NWM0-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-196: Missing.
         510-510: A → AHGSSTKQQPGHLFSSKCPEQPLDANRGAVK

    Note: Does not seem to display oxidase activity towards spermidine or N1-acetyl-spermine, but this has to be confirmed. No experimental confirmation available.
    Show »
    Length:389
    Mass (Da):43,553
    Checksum:iF8AF920F5B10EBA9
    GO
    Isoform 6 (identifier: Q9NWM0-6) [UniParc]FASTAAdd to basket
    Also known as: SMO5, SMOX5

    The sequence of this isoform differs from the canonical sequence as follows:
         510-510: A → AHGSSTKQQPGHLFSSKCPEQPLDANRGAVK

    Note: Substrate specificities and affinities comparable to those of isoform 1.
    Show »
    Length:585
    Mass (Da):65,007
    Checksum:i7B1744F671906B9B
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti16S → R in AAK55764 (PubMed:12398765).Curated1
    Sequence conflicti60I → V in AAK55765 (PubMed:12398765).Curated1
    Sequence conflicti156H → Y in AAK55764 (PubMed:12398765).Curated1
    Sequence conflicti290T → A in BAB15288 (PubMed:14702039).Curated1
    Sequence conflicti320C → R in AAK55763 (PubMed:11454677).Curated1
    Sequence conflicti320C → R in ABM01872 (PubMed:18422650).Curated1
    Sequence conflicti372F → L in AAN77119 (PubMed:12398765).Curated1
    Sequence conflicti431E → G in AAN77119 (PubMed:12398765).Curated1
    Sequence conflicti431E → G in ABM01872 (PubMed:18422650).Curated1
    Sequence conflicti504T → A in AAK55764 (PubMed:12398765).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_059114301R → P. Corresponds to variant dbSNP:rs6084654Ensembl.1
    Natural variantiVAR_036546340Q → K in a breast cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_019531522H → Y1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0111231 – 196Missing in isoform 5. 1 PublicationAdd BLAST196
    Alternative sequenceiVSP_011124146 – 510Missing in isoform 3. 1 PublicationAdd BLAST365
    Alternative sequenceiVSP_011125282 – 334Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST53
    Alternative sequenceiVSP_011126510A → AHGSSTKQQPGHLFSSKCPE QPLDANRGAVK in isoform 4, isoform 5 and isoform 6. 3 Publications1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY033889 mRNA Translation: AAK55763.1
    AY033890 mRNA Translation: AAK55764.1
    AY033891 mRNA Translation: AAK55765.1
    AF519179 mRNA Translation: AAN77119.1
    EF032141 mRNA Translation: ABM01872.1
    AY358104 mRNA Translation: AAQ88471.1
    AK000753 mRNA Translation: BAA91360.1
    AK025938 mRNA Translation: BAB15288.1
    AL121675 Genomic DNA No translation available.
    CH471133 Genomic DNA Translation: EAX10460.1
    CH471133 Genomic DNA Translation: EAX10461.1
    CH471133 Genomic DNA Translation: EAX10457.1
    CH471133 Genomic DNA Translation: EAX10458.1
    CH471133 Genomic DNA Translation: EAX10459.1
    CH471133 Genomic DNA Translation: EAX10462.1
    BC000669 mRNA Translation: AAH00669.1
    AL162058 mRNA Translation: CAB82396.1
    CCDSiCCDS13075.1 [Q9NWM0-1]
    CCDS13076.1 [Q9NWM0-2]
    CCDS13077.1 [Q9NWM0-3]
    CCDS13078.1 [Q9NWM0-4]
    CCDS74702.1 [Q9NWM0-6]
    PIRiT47142
    RefSeqiNP_001257620.1, NM_001270691.1 [Q9NWM0-6]
    NP_787033.1, NM_175839.2 [Q9NWM0-1]
    NP_787034.1, NM_175840.2 [Q9NWM0-2]
    NP_787035.1, NM_175841.2 [Q9NWM0-3]
    NP_787036.1, NM_175842.2 [Q9NWM0-4]
    XP_011527563.1, XM_011529261.2 [Q9NWM0-6]
    UniGeneiHs.433337

    Genome annotation databases

    EnsembliENST00000278795; ENSP00000278795; ENSG00000088826 [Q9NWM0-4]
    ENST00000305958; ENSP00000307252; ENSG00000088826 [Q9NWM0-1]
    ENST00000339123; ENSP00000344595; ENSG00000088826 [Q9NWM0-2]
    ENST00000346595; ENSP00000341775; ENSG00000088826 [Q9NWM0-3]
    ENST00000379460; ENSP00000368773; ENSG00000088826 [Q9NWM0-1]
    ENST00000621355; ENSP00000478305; ENSG00000088826 [Q9NWM0-6]
    GeneIDi54498
    KEGGihsa:54498
    UCSCiuc002wkk.2 human [Q9NWM0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiSMOX_HUMAN
    AccessioniPrimary (citable) accession number: Q9NWM0
    Secondary accession number(s): A2A2P5
    , A2A2P6, A8BE87, D3DVZ4, Q5TE26, Q5TE27, Q6UY28, Q8IX00, Q96LC3, Q96LC4, Q96QT3, Q9BW38, Q9H6H1, Q9NP51, Q9NPY1, Q9NPY2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: October 1, 2000
    Last modified: May 23, 2018
    This is version 143 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

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