Information on EC 1.5.3.16 -

Information on EC 1.5.3.16 - spermine oxidase:

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EC NUMBER	COMMENTARY
1.5.3.16	-

RECOMMENDED NAME	GeneOntology No.
spermine oxidase	GO:0052901

REACTION	REACTION DIAGRAM	COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2		-	-	-	-
spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2		-	Homo sapiens	Q9NWM0-1	654435

REACTION TYPE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

PATHWAY	KEGG Link	MetaCyc Link
spermine and spermidine degradation I	-	PWY-6117

SYSTEMATIC NAME

IUBMB Comments

spermidine:oxygen oxidoreductase (spermidine-forming)

The enzyme from Arabidopsis thaliana (AtPAO1) oxidizes norspermine to norspermidine with high efficiency [3]. The mammalian enzyme, encoded by the SMOX gene, is a cytosolic enzyme that catalyses the oxidation of spermine at the exo (three-carbon) side of the tertiary amine. No activity with spermidine. Weak activity with N1-acetylspermine. A flavoprotein (FAD). Differs in specificity from EC 1.5.3.13 (N1-acetylpolyamine oxidase), EC 1.5.3.14 (polyamine oxidase (propane-1,3-diamine-forming)), EC 1.5.3.15 (N8-acetylspermidine oxidase (propane-1,3-diamine-forming) and EC 1.5.3.17 (non-specific polyamine oxidase).

SYNONYMS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
AtPAO1	Arabidopsis thaliana	Q9FNA2	-	676604
AtPAO4	Arabidopsis thaliana	Q8H191	-	694651
hSMO	Homo sapiens	-	-	692978
mSMO	Mus musculus	-	-	673538, 690692, 691051, 692157, 692970
mSMOalpha	Mus musculus	-	-	691035
mSMOmu	Mus musculus	-	-	691035
mSMOmu	Mus musculus	-	splice variant	692157, 692280
PAO4	Arabidopsis thaliana	-	-	712608, 713263
PAOh1	Homo sapiens	-	-	691600
PAOh1/SMO	Homo sapiens	Q9NWM0-1	-	654435
SMO	Mus musculus	-	-	692648
SMO(PAOh1)	Homo sapiens	-	-	690802, 692977
SMO/PAOh1	Homo sapiens	-	-	691601, 692298
SMO5	Homo sapiens	-	splice variant protein	692298
SMOX	Homo sapiens	-	-	712194
spermine oxidase	Mus musculus	-	-	673538, 690692, 691051, 692157, 692970
spermine oxidase	Homo sapiens	-	-	690802, 691601, 692298, 692977, 694943

CAS REGISTRY NUMBER	COMMENTARY
No entries in this field

ORGANISM	COMMENTARY	LITERATURE	SEQUENCE CODE	SEQUENCE DB	SOURCE
Arabidopsis thaliana	-	676604	Q9FNA2	SwissProt
Arabidopsis thaliana	; isozyme AtPAO4	694651	Q8H191	SwissProt
Arabidopsis thaliana	isoform PAO1	712608	Q9FNA2	SwissProt
Arabidopsis thaliana	isoform PAO4	712608	Q8H191	SwissProt
Arabidopsis thaliana	PAO1	713263	Q9FNA2	SwissProt
Arabidopsis thaliana	PAO4	713263	Q8H191	SwissProt
Ascaris suum	-	690790, 694540	-	-
Homo sapiens	-	654435	Q9NWM0-1	SwissProt
Homo sapiens	-	690800, 691600, 692298	Q9NWM0	SwissProt
Homo sapiens	-	690802, 691601, 692298, 692977, 692978, 694943, 711241, 711592, 712194, 712558	-	-
Mus musculus	-	673538, 691051, 692648, 711592	-	-
Mus musculus	-	690692, 690800, 691035, 692280, 692970, 710832	Q99K82	SwissProt
Mus musculus	adult male DBA2 mice	692157	Q99K82	SwissProt

GENERAL INFORMATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
malfunction	Arabidopsis thaliana	Q8H191	AtPAO4 deficiency induces alterations in the expression of genes related to the drought stress response and flavonoid biosynthesis	694651

SUBSTRATE	PRODUCT	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY/ Substrate	LITERATURE/ Substrate	COMMENTARY/ Product	LITERATURE/ Product	Reversibility r=reversible ir=irreversible ?=not specified
alpha-methylspermine + O2 + H2O	?		Homo sapiens	-	-	692978	-	-	?
N1-acetylspermine + O2 + H2O	spermidine + 3-acetamidopropanal + H2O2		Homo sapiens	-	-	711241	-	-	?
N1-acetylspermine + O2 + H2O	?		Homo sapiens	Q9NWM0	very poor substrate	690800	-	-	?
N1-acetylspermine + O2 + H2O	?		Homo sapiens	Q9NWM0-1	weak activity	654435	-	-	?
N1-acetylspermine + O2 + H2O	?		Homo sapiens	-	less than 10% of the activity with spermine, SMO/PAOh1, less than 10% of the activity with spermine, splice variant SMO5	692298	-	-	?
N1-acetylspermine + O2 + H2O	spermine + 3-acetamidopropanal + H2O2		Arabidopsis thaliana	Q9FNA2	-	676604	-	-	?
N1-acetylspermine + O2 + H2O	spermidine + acetaminopropanal		Arabidopsis thaliana	Q8H191, Q9FNA2	-	712608	-	-	?
N1-acetylspermine + O2 + H2O	spermidine + acetaminopropanal		Arabidopsis thaliana	Q8H191, Q9FNA2	less than 10% of the activity with norspermine	713263	-	-	?
N1-monoethylspermine + O2 + H2O	spermidine + ?		Homo sapiens	Q9NWM0	98% of the activity with spermine	690800	-	-	?
norspermidine + O2 + H2O	?		Ascaris suum	-	-	690790	-	-	?
norspermine + O2 + H2O	?		Ascaris suum	-	-	690790	-	-	?
norspermine + O2 + H2O	?		Arabidopsis thaliana	Q9FNA2	-	676604	-	-	?
norspermine + O2 + H2O	? + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	-	712608	-	-	?
norspermine + O2 + H2O	? + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	best substrate	713263	-	-	?
spermidine + O2 + H2O	putrescine + 3-aminopropanal + H2O2		Ascaris suum	-	-	690790	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Homo sapiens	-	-	711241	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Ascaris suum	-	-	690790	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Mus musculus	-	-	691035, 692970, 710832	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Homo sapiens	Q9NWM0	-	690800	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Arabidopsis thaliana	Q9FNA2	-	676604	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Arabidopsis thaliana	Q8H191	-	694651	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Homo sapiens	Q9NWM0	SMO may contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-aminopropanal	690800	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Arabidopsis thaliana	Q8H191	AtPAO4 specifically catalyzes the conversion of spermine to spermidine under the assay conditions	694651	-	-	?
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Mus musculus	-	strongly favours spermine over N1-acetylspermine, fails to act on N1-acetylspermidine, spermidine or the preferred PAO substrate, N1,N12-diacetylspermine	690800	-	-	?
spermine + O2 + H2O	?		Mus musculus	-	-	673538, 692648	-	-	?
spermine + O2 + H2O	?		Homo sapiens	-	-	690802, 691601, 692978, 691600	-	-	?
spermine + O2 + H2O	?		Homo sapiens	Q9NWM0-1	-	654435	-	-	?
spermine + O2 + H2O	?		Homo sapiens	-	exhibits a strong preference for spermine as the primary substrate over all other naturally occurring polyamines, SMO/PAOh1, exhibits a strong preference for spermine as the primary substrate over all other naturally occurring polyamines, splice variant SMO5	692298	-	-	?
spermine + O2 + H2O	?		Mus musculus	-	mutant mSMOmuDELTA (with a deletion of the nuclear domain A) is not active on spermidine, N1-acetylspermidine or N1-acetylspermine	692280	-	-	?
spermine + O2 + H2O	?		Mus musculus	Q99K82	purified isoform mSMOmu oxidizes specifically spermine and is not active on spermidine, N1-acetylspermidine and N1-acetylspermine	692157	-	-	?
spermine + O2 + H2O	?		Mus musculus	Q99K82	the mMSO catalytic mechanism is consistent with a simple four-step kinetic scheme. The enzyme is unable to oxidize other free or acetylated polyamines	690692	-	-	?
spermine + O2 + H2O	spermidine + 3-acetaminopropanal + H2O2		Arabidopsis thaliana	Q9FNA2	enzyme is involved in a polyamine back-conversion pathway	676604	-	-	?
spermine + O2 + H2O	spermidine + aminopropanal + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	-	712608	-	-	?
spermine + O2 + H2O	spermidine + aminopropanal + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	about 20% of the activity with norspermine	713263	-	-	?
spermine + O2 + H2O	spermidine + aminopropanal + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	bets substrate	713263	-	-	?
thermospermine + O2 + H2O	? + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	-	712608	-	-	?
thermospermine + O2 + H2O	? + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	about 10% of the activity with spermine	713263	-	-	?
thermospermine + O2 + H2O	? + H2O2		Arabidopsis thaliana	Q8H191, Q9FNA2	about 65% of the activity with norspermine	713263	-	-	?
tryptamine + O2 + H2O	?		Ascaris suum	-	-	690790	-	-	?
benzylamidine + O2 + H2O	?		Ascaris suum	-	-	690790	-	-	?
additional information	?	-	Arabidopsis thaliana	Q9FNA2	no activity with spermidine	676604	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191	AtPAO4 deficiency induces alterations in the expression of genes related to the drought stress response and flavonoid biosynthesis	694651	-	-	-
additional information	?	-	Mus musculus	-	in mammalian cells, polyamine catabolism seems to be mediated by the activity of two enzymes, PAO and SMO	692970	-	-	-
additional information	?	-	Homo sapiens	-	PAOh1 is upregulated in response to polyamine analogue exposure. N1,N11-bis(ethyl)norspermine results in 5fold induction of PAO mRNA and a more than 3-fold induction of PAO activity	691600	-	-	-
additional information	?	-	Mus musculus	-	spermine oxidase activity is a direct oxidative stress inducer of DNA damage, thus rendering cells more sensitive to radiation and apoptosis	691035	-	-	-
additional information	?	-	Mus musculus	-	spermine oxidase overactivity can deliver sublethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ornithine decarboxylase and spermidine/spermine N1-acetyltransferase	691051	-	-	-
additional information	?	-	Homo sapiens	-	the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA	690802	-	-	-
additional information	?	-	Homo sapiens	-	TNF-alpha exposure leads to the induction of SMO/PAOh1, which produces sufficient H2O2 to result in potentially mutagenic DNA damage and presents a molecular mechanism by which general inflammation can contribute directly to the development of cancer	691601	-	-	-
additional information	?	-	Mus musculus	-	fails to act upon spermidine, N1-acetylpolyamines, putrescine and N1-acetylcadaverine	692970	-	-	-
additional information	?	-	Ascaris suum	-	N-acetylated polyamines and diamines, e.g. Nl-acetylspermidine, N8-acetylspermidine, N-acetylspermine, N1,N12-diacetylspermine, putrescine, cadaverine and histamine, are not accepted as substrates. Bis(benzyl)polyamines, such as MDL 27695 and MDL 27391, are not substrates	690790	-	-	-
additional information	?	-	Homo sapiens	-	no activity with N1-acetylspermine, spermidine, alpha-methylspermidine. No production of spermidine from bis-alpha-methylspermine, hSMO	692978	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191	no activity with putrescine, spermidine, N1-acetylspermine	694651	-	-	-
additional information	?	-	Mus musculus	Q99K82	no activity with spermidine and putrescine	690692	-	-	-
additional information	?	-	Homo sapiens	Q9NWM0-1	no activity with spermidine. No oxidation of N1,N11-bis(ethyl)norspemine, N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane, N1-ethyl-N11-(cycloheptyl)methyl-4,8,diazaundecane, (S)-N1-(2-methyl-1-butyl)-N11-ethyl-4,8,diazaundecane, SL-11144, SL-11150, SL-11156 and SL-11093	654435	-	-	-
additional information	?	-	Homo sapiens	Q9NWM0	no activity with: spermidine, N1,N12-diacetylspermine, N1,N12-diethylspermine, N1,N14-diethylhomospermine, MDL-72527, N1,N11-diethylnorspermine	690800	-	-	-
additional information	?	-	Homo sapiens	-	SMO/PAOh1 exhibits no oxidase activity when using N1,N12-diacetylspermine, N1-acetylspermidine, N8-acetylspermidine, spermidine, or the polyamine analogues, bis(ethyl)norspermine or N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane, splice variant SMO5 exhibits no oxidase activity when using N1,N12-diacetylspermine, N1-acetylspermidine, N8-acetylspermidine, spermidine, or the polyamine analogues, bis(ethyl)norspermine or N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane	692298	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191	peroxisomal polyamine oxidase AtPAO4 is involved in the catabolism of polyamines in leaves, overview	694651	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191, Q9FNA2	no substrate: spermidine, N1-acetylspermine, norspermine	713263	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191, Q9FNA2	no substrate: spermidine. Comparative study of the catalytic properties of recombinant AtPAO1, AtPAO2, AtPAO3, and AtPAO4. All four enzymes strongly resemble their mammalian counterparts, being able to oxidize the common polyamines Spd and/or Spm through a polyamine backconversion pathway	712608	-	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191, Q9FNA2	spermidine is oxidized with very low efficiency. Comparative study of the catalytic properties of recombinant AtPAO1, AtPAO2, AtPAO3, and AtPAO4. All four enzymes strongly resemble their mammalian counterparts, being able to oxidize the common polyamines Spd and/or Spm through a polyamine backconversion pathway	712608	-	-	-

NATURAL SUBSTRATES	NATURAL PRODUCTS	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY SUBSTRATE	LITERATURE (Substrate)	COMMENTARY PRODUCT	LITERATURE (Product)
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Arabidopsis thaliana	Q8H191	-	694651	-	-
spermine + O2 + H2O	spermidine + 3-aminopropanal + H2O2		Homo sapiens	Q9NWM0	SMO may contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-aminopropanal	690800	-	-
spermine + O2 + H2O	spermidine + 3-acetaminopropanal + H2O2		Arabidopsis thaliana	Q9FNA2	enzyme is involved in a polyamine back-conversion pathway	676604	-	-
additional information	?	-	Arabidopsis thaliana	Q9FNA2	no activity with spermidine	676604	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191	AtPAO4 deficiency induces alterations in the expression of genes related to the drought stress response and flavonoid biosynthesis	694651	-	-
additional information	?	-	Mus musculus	-	in mammalian cells, polyamine catabolism seems to be mediated by the activity of two enzymes, PAO and SMO	692970	-	-
additional information	?	-	Homo sapiens	-	PAOh1 is upregulated in response to polyamine analogue exposure. N1,N11-bis(ethyl)norspermine results in 5fold induction of PAO mRNA and a more than 3-fold induction of PAO activity	691600	-	-
additional information	?	-	Mus musculus	-	spermine oxidase activity is a direct oxidative stress inducer of DNA damage, thus rendering cells more sensitive to radiation and apoptosis	691035	-	-
additional information	?	-	Mus musculus	-	spermine oxidase overactivity can deliver sublethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ornithine decarboxylase and spermidine/spermine N1-acetyltransferase	691051	-	-
additional information	?	-	Homo sapiens	-	the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA	690802	-	-
additional information	?	-	Homo sapiens	-	TNF-alpha exposure leads to the induction of SMO/PAOh1, which produces sufficient H2O2 to result in potentially mutagenic DNA damage and presents a molecular mechanism by which general inflammation can contribute directly to the development of cancer	691601	-	-
additional information	?	-	Arabidopsis thaliana	Q8H191	peroxisomal polyamine oxidase AtPAO4 is involved in the catabolism of polyamines in leaves, overview	694651	-	-

COFACTOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
FAD	Arabidopsis thaliana	Q9FNA2	all FAD molecules in the purified enzyme are catalytically active	676604	2D-image
FAD	Mus musculus	-	non-covalently bound to the enzyme	690692	2D-image
FAD	Ascaris suum	-	-	690790	2D-image
FAD	Homo sapiens, Mus musculus	-	-	690800	2D-image
FAD	Mus musculus	-	flavin/mSMO stoichiometry of 1:1	692970	2D-image
FAD	Arabidopsis thaliana	Q8H191	-	694651	2D-image

METALS and IONS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
additional information	Ascaris suum	-	copper and iron are not cofactors	690790

INHIBITORS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
1,12-diaminododecane	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
1,8-diaminooctane	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
agmatine	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
bis(ethyl)norspermine	Homo sapiens	-	structure modeling analysis of complex formed with SMO	711592	-
bis(ethyl)norspermine	Mus musculus	-	-	711592	-
dithioerythritol	Ascaris suum	-	up to 0.010 mM increase the enzyme activity, higher concentrations inhibited it	690790	2D-image
dithiothreitol	Ascaris suum	-	up to 0.010 mM increase the enzyme activity, higher concentrations inhibited it	690790	2D-image
guazatine	Mus musculus	-	-	673538	2D-image
guazatine	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
Iproniazid	Ascaris suum	-	0.01 mM, 87% inhibition	690790	2D-image
Isoniazid	Ascaris suum	-	0.01 mM, 81% inhibition	690790	2D-image
MDL 27391	Ascaris suum	-	-	690790	2D-image
MDL 27695	Ascaris suum	-	-	690790	2D-image
MDL 72145	Ascaris suum	-	inhibited in a time-dependent manner. Half-life under saturation conditions is 0.8 min. MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections	694540	2D-image
MDL 72527	Mus musculus	-	-	691035	2D-image
MDL 72527	Ascaris suum	-	the specific inhibitor of mammalian polyamine oxidase, has no effect on the Ascaris suum enzyme	694540	2D-image
MDL-72527	Homo sapiens	-	0.2 mM, 41% inhibition	690800	2D-image
MDL72527	Mus musculus	-	-	673538, 692970	2D-image
N,N' -bis(2,3-butadienyl)-1,4-butanediamine	Mus musculus	-	i.e. MDL72527	711592	2D-image
N,N1-bis(2,3-butadienyl)-1,4-butanediamine	Mus musculus	-	i.e. MDL72527, competitive. If incubated for longer times, MDL72527 yields irreversible inhibition of the enzyme with a half-life of 15 min at 0.1 mM MDL72527	690692	2D-image
N-prenylagmatine	Mus musculus	-	-	673538	2D-image
N-prenylagmatine	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
N1,N11-diethylnorspermine	Homo sapiens	-	0.2 mM, 21% inhibition	690800	2D-image
N1,N12-diethylspermine	Homo sapiens	-	0.2 mM, 15% inhibition	690800	2D-image
N1,N14-diethylhomospermine	Homo sapiens	-	0.2 mM, 49% inhibition	690800	2D-image
N1,N4-bis(2,3-butadienyl)-1,4-butanediamine	Homo sapiens	Q9NWM0-1	i.e. MDL72527, 0.25 mM, more than 95% inhibition	654435	2D-image
N1,N4-bis(2,3-butadienyl)-1,4-butanediamine	Homo sapiens	-	i.e. MDL72527	691600	2D-image
N1-(n-octanesulfonyl)spermine	Homo sapiens	-	0.2 mM, 86% inhibition	690800	2D-image
N1-ethyl-N11-(cyclopropyl)-methyl-4,8-diazaundecane	Homo sapiens	-	structure modeling analysis of complex formed with SMO	711592	-
N1-ethyl-N11-(cyclopropyl)-methyl-4,8-diazaundecane	Mus musculus	-	-	711592	-
NEM	Ascaris suum	-	0.01 mM, 85% inhibition	690790	2D-image
SL-11144	Homo sapiens	Q9NWM0-1	potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM	654435	2D-image
SL-11150	Homo sapiens	Q9NWM0-1	potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM	654435	2D-image
SL-11158	Homo sapiens	Q9NWM0-1	potent inhibitor of PAOh1/SMO, IC50 below 0.01 mM	654435	2D-image
spermidine	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
spermidine	Homo sapiens	-	0.2 mM, 41% inhibition	690800	2D-image
MDL72527	Arabidopsis thaliana	Q9FNA2	-	676604	2D-image
additional information	Homo sapiens	Q9NWM0-1	no inhibition by N1-ethyl-N11-(cycloheptyl)methyl-4,8,diazaundecane	654435	-
additional information	Mus musculus	-	no inhibition at pH 8.5: 1,8-diaminooctane, 1,12-diaminododecane (inhibitor of polyamine oxidase). Comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups The data provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities	673538	-
additional information	Ascaris suum	-	the polyamine oxidase inhibitor MDL 72527 has no effect on the parasite polyamine oxidase activity	690790	-

ACTIVATING COMPOUND	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
N1,N11-diethylnorspermine	Homo sapiens	-	polyamine analogue with clinical relevance as an experimental anticancer agent. Treatment of human C-28/I2 chondrocytes rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels	712558	2D-image

KM VALUE [mM]	KM VALUE [mM] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.034	-	alpha-methylspermine	Homo sapiens	-	without benzyladehyde, kinetic value for the unmethylated end, hSMO	692978	2D-image
0.067	-	alpha-methylspermine	Homo sapiens	-	without benzyladehyde, kinetic value for the unmethylated end, hSMO	692978	2D-image
0.051	-	N1-acetylspermine	Homo sapiens	Q9NWM0-1	37�C, pH 8.0	654435	2D-image
0.47	-	N1-acetylspermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
0.47	-	N1-acetylspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
0.49	2	N1-acetylspermine	Homo sapiens	-	pH 8.3, 25�C	711241	2D-image
5	-	norspermidine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
0.09	-	norspermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
0.9	-	norspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
2	-	norspermine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
0.66	-	spermidine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
0.0005	-	spermine	Homo sapiens	-	splice variant SMO5	692298	2D-image
0.0006	-	spermine	Homo sapiens	-	SMO/PAOh1	692298	2D-image
0.00163	-	spermine	Homo sapiens	Q9NWM0-1	37�C, pH 8.0	654435	2D-image
0.018	-	spermine	Homo sapiens	-	37�C	691600	2D-image
0.02	-	spermine	Homo sapiens	-	hSMO	692978	2D-image
0.021	-	spermine	Mus musculus	-	mutant K367M, pH 8.5, 25�C	710832	2D-image
0.047	-	spermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 7.5, temperature not specified in the publication	712608	2D-image
0.09	-	spermine	Mus musculus	-	pH 8.0, 37�C, purified recombinant-tagged form enzyme	692970	2D-image
0.11	-	spermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
0.12	-	spermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
0.15	-	spermine	Mus musculus	Q99K82	pH 8.5, isoform mSMOmu	692157	2D-image
0.17	-	spermine	Mus musculus	-	-	690692	2D-image
0.19	-	spermine	Homo sapiens	-	pH 8.3, 25�C	711241	2D-image
0.22	-	spermine	Mus musculus	-	pH 8.5, mutant mSMOmuDELTA (with a deletion of the nuclear domain A)	692280	2D-image
0.23	-	spermine	Arabidopsis thaliana	Q8H191	25�C, pH 8; recombinant His-tagged isozyme AtPAO4	694651	2D-image
0.242	-	spermine	Mus musculus	-	wild-type, pH 8.5, 25�C	710832	2D-image
0.35	-	spermine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
0.53	-	spermine	Mus musculus	-	mutant H82Q, pH 8.5, 25�C	710832	2D-image
0.02	-	thermospermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
2.5	-	tryptamine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
1.6	-	benzylamidine	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
additional information	-	additional information	Homo sapiens	-	steady-state kinetic pattern is ping-pong. Reduction of SMO by spermine in the absence of oxygen is biphasic. The rate constant for the rapid phase varies with the substrate concentration, with a limiting value k3 of 49 s-1 and an apparent Kd value of 48 microM at pH 8.3. The rate constant for the slow step is independent of the spermine concentration. The kinetics of the oxidative half-reaction depend on the aging time after the spermine and enzyme are mixed in a double-mixing experiment. The results establish the existence of more than one pathway for the reaction of the reduced flavin intermediate with oxygen. The active form of spermine has three charged nitrogens	711241	-

TURNOVER NUMBER [1/s]	TURNOVER NUMBER MAXIMUM[1/s]	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.014	-	N1-acetylspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 7.5, temperature not specified in the publication	712608	2D-image
0.2	-	N1-acetylspermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
0.2	-	N1-acetylspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
0.28	-	N1-acetylspermine	Homo sapiens	-	SMO/PAOh1; splice variant SMO5	692298	2D-image
0.45	-	norspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 7.5, temperature not specified in the publication	712608	2D-image
6.9	-	norspermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
6.9	-	norspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
0.0208	-	spermine	Mus musculus	-	pH 8.5, mutant mSMOmuDELTA (with a deletion of the nuclear domain A)	692280	2D-image
0.024	-	spermine	Mus musculus	-	mutant H82Q, pH 8.5, 25�C	710832	2D-image
0.1	-	spermine	Mus musculus	-	mutant K367M, pH 8.5, 25�C	710832	2D-image
1.4	-	spermine	Arabidopsis thaliana	Q8H191	25�C, pH 8; recombinant His-tagged isozyme AtPAO4	694651	2D-image
2.5	-	spermine	Mus musculus	Q99K82	pH 8.5, isoform mSMOmu	692157	2D-image
2.5	-	spermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image
2.7	-	spermine	Arabidopsis thaliana	Q9FNA2	pH 8.0	676604	2D-image
3.11	-	spermine	Homo sapiens	-	splice variant SMO5	692298	2D-image
3.57	-	spermine	Mus musculus	-	wild-type, pH 8.5, 25�C	710832	2D-image
4.5	-	spermine	Mus musculus	-	pH 8.0, 37�C, purified recombinant-tagged form enzyme	692970	2D-image
4.6	-	spermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 7.5, temperature not specified in the publication	712608	2D-image
4.8	-	spermine	Mus musculus	-	-	690692	2D-image
6.6	-	spermine	Homo sapiens	-	pH 8.3, 25�C	711241	2D-image
7.55	-	spermine	Homo sapiens	-	SMO/PAOh1	692298	2D-image
0.1	-	thermospermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 7.5, temperature not specified in the publication	712608	2D-image
5.7	-	thermospermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	2D-image

kcat/KM VALUE [1/mMs^-1]	kcat/KM VALUE [1/mMs^-1] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.43	-	N1-acetylspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	14158
0.8	-	N1-acetylspermine	Homo sapiens	-	pH 8.3, 25�C	711241	14158
7.7	-	norspermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	136462
5e-05	-	spermine	Mus musculus	-	mutant H82Q, pH 8.5, 25�C	710832	16688
0.0015	-	spermine	Mus musculus	-	wild-type, pH 8.5, 25�C	710832	16688
0.005	-	spermine	Mus musculus	-	mutant K367M, pH 8.5, 25�C	710832	16688
20.8	-	spermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	16688
37	-	spermine	Homo sapiens	-	pH 8.3, 25�C	711241	16688
285	-	thermospermine	Arabidopsis thaliana	Q8H191, Q9FNA2	pH 8.0, temperature not specified in the publication	712608	263998

Ki VALUE [mM]	Ki VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.0117	-	1,12-diaminododecane	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.293	-	1,8-diaminooctane	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.147	-	agmatine	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.38	-	bis(ethyl)norspermine	Mus musculus	-	pH 8.5, 25�C	711592	-
0.0004	-	guazatine	Mus musculus	-	pH 8.5, 25�C	673538	2D-image
0.0007	-	guazatine	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.02	-	MDL 27695	Ascaris suum	-	pH 8.5, 37�C	690790	2D-image
0.0009	-	MDL 72145	Ascaris suum	-	-	694540	2D-image
0.063	-	MDL72527	Mus musculus	-	pH 8.5, 25�C	673538	2D-image
0.1373	-	MDL72527	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.063	-	N,N' -bis(2,3-butadienyl)-1,4-butanediamine	Mus musculus	-	pH 8.5, 25�C	711592	2D-image
0.063	-	N,N1-bis(2,3-butadienyl)-1,4-butanediamine	Mus musculus	-	-	690692	2D-image
0.004	-	N-prenylagmatine	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image
0.046	-	N-prenylagmatine	Mus musculus	-	pH 8.5, 25�C	673538	2D-image
0.085	-	N1-ethyl-N11-(cyclopropyl)-methyl-4,8-diazaundecane	Mus musculus	-	pH 8.5, 25�C	711592	-
0.546	-	spermidine	Arabidopsis thaliana	Q9FNA2	pH 8.0, substrate: spermine	676604	2D-image

IC50 VALUE [mM]	IC50 VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg]	SPECIFIC ACTIVITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
2.3	-	Ascaris suum	-	-	690790
5	-	Mus musculus	-	-	690692

pH OPTIMUM	pH MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
7.5	8.5	Arabidopsis thaliana	Q8H191	; recombinant His-tagged isozyme AtPAO4 with substrate spermine	694651
8	-	Arabidopsis thaliana	Q9FNA2	substrate: spermine or norspermine	676604
8	-	Mus musculus	-	in Na-phosphate buffer	692970
8.5	-	Mus musculus	-	-	690692
8.5	-	Ascaris suum	-	-	690790
8.5	-	Mus musculus	Q99K82	-	692157
8.5	-	Mus musculus	-	mutant mSMOmuDELTA (with a deletion of the nuclear domain)	692280
8.5	-	Mus musculus	-	wild-type and mutant H82Q	710832
9	9.5	Mus musculus	-	mutant K367M	710832
9.5	-	Homo sapiens	-	-	690800

pH RANGE	pH RANGE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
7	9	Arabidopsis thaliana	Q9FNA2	pH 7: about 60% of maximal activity, pH 9.0: about 60% of maximal activity, substrate: spermine; pH 7: about 80% of maximal activity, pH 9.0: about 60% of maximal activity, substrate: norspermine	676604

TEMPERATURE OPTIMUM	TEMPERATURE OPTIMUM MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE RANGE	TEMPERATURE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

pI VALUE	pI VALUE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
7.8	-	Ascaris suum	-	isoelectric focusing	690790

SOURCE TISSUE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	SOURCE
A-549 cell	Homo sapiens	-	-	690802
BEAS-2B cell	Homo sapiens	-	-	691601
brain	Mus musculus	Q99K82	splice variant mSMO	692157
brain	Homo sapiens	-	-	712194
breast cancer cell	Mus musculus	-	-	690800
breast cancer cell	Homo sapiens	-	-	711592
breast cancer cell line	Homo sapiens	-	the antiproliferative effects of analogue N1,N1-bis(ethyl)norspermine in MDA-MB-231 cells are mediated in part through the production of H2O2 by SMO(PAOh1) and by the export of acetylated polyamines formed by the activity of spermidine/spermine N1-acetyltransferase	692977
C-28/I2 cell	Homo sapiens	-	-	712558
C2C12 cell	Mus musculus	-	; SMO transcript accumulation and enzymatic activity increases during C2C12 cell differentiation and correlates with the decrease of spermine content. Increased spermine oxidase (SMO) activity is a differentiation marker of myogenic C2C12 cells	692648
cerebellum	Mus musculus	Q99K82	splice variant mSMO	692157
chondrocyte	Homo sapiens	-	-	712558
cotyledon	Arabidopsis thaliana	Q8H191	greening	694651
flower	Arabidopsis thaliana	-	-	694651, 713263
heart	Mus musculus	Q99K82	splice variant mSMO	692157
intestine	Mus musculus	Q99K82	poor activity, splice variant mSMO	692157
kidney	Mus musculus	Q99K82	splice variant mSMO	692157
leaf	Arabidopsis thaliana	Q8H191	-	694651
liver	Mus musculus	Q99K82	poor activity, splice variant mSMO	692157
N18TG2 cell	Mus musculus	-	-	691051
neuroblastoma cell	Mus musculus	-	-	691035
prostate	Homo sapiens	-	tissues from patients diagnosed with prostate cancer and prostatic intraepithelial neoplasia exhibit, on average, locally increased spermine oxidase (SMO) expression in regions of prostatic disease and higher overall SMO expression in prostatic epithelial cells compared to healthy individuals	694943
root	Arabidopsis thaliana	Q8H191	; AtPAO4 is the major isoform in root peroxisomes	694651
root	Arabidopsis thaliana	Q8H191, Q9FNA2	expressed at higher level all over young seedlings including roots	713263
seedling	Arabidopsis thaliana	Q8H191	-	694651
seedling	Arabidopsis thaliana	Q8H191, Q9FNA2	expressed at higher level all over young seedlings including roots	713263
silique	Arabidopsis thaliana	Q8H191	-	694651
skeletal muscle	Mus musculus	Q99K82	splice variant mSMO	692157
spleen	Mus musculus	Q99K82	poor activity, splice variant mSMO	692157
stem	Arabidopsis thaliana	Q8H191	-	694651
testis	Mus musculus	Q99K82	splice variant mSMO	692157
lung	Mus musculus	Q99K82	poor activity, splice variant mSMO	692157
additional information	Arabidopsis thaliana	Q8H191	isozyme AtPAO4 transcript is abundantly expressed in roots, flowers and greening cotyledons, but more poorly expressed in other tissues	694651
additional information	Arabidopsis thaliana	Q8H191, Q9FNA2	in the mature stage expression is ubiquitous with rather lower level in stem	713263

LOCALIZATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	GeneOntology No.	LITERATURE	SOURCE
cytoplasm	Mus musculus	Q99K82	isoform mSMOmu is present in both nuclear and cytoplasmic compartments in N18TG2 cells	5737	692157
cytoplasm	Mus musculus	-	SMOalpha splice variant protein, exclusively in cytoplasm	5737	692648
cytosol	Mus musculus	-	splice variant mSMOmu is present in both nuclear and cytoplasmic compartments, two short protein domains are responsible for the nuclear localization of splice variant mSMOmu	5829	692280
cytosol	Homo sapiens	-	SMO5; SMO/PAOh1	5829	692298
nucleus	Mus musculus	-	-	5634	691035
nucleus	Mus musculus	Q99K82	isoform mSMOmu is present in both nuclear and cytoplasmic compartments in N18TG2 cells	5634	692157
nucleus	Mus musculus	-	splice variant mSMOmu is present in both nuclear and cytoplasmic compartments, two short protein domains are responsible for the nuclear localization of splice variant mSMOmu	5634	692280
nucleus	Homo sapiens	-	SMO5; SMO/PAOh1	5634	692298
nucleus	Mus musculus	-	SMOmu splice variant; SMOmy splice variant protein	5634	692648
peroxisome	Arabidopsis thaliana	Q8H191	; AtPAO4 is the major isoform in root peroxisomes	5777	694651

PDB	SCOP	CATH	ORGANISM
No entries in this field

MOLECULAR WEIGHT	MOLECULAR WEIGHT MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

SUBUNITS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
?	Homo sapiens	Q9NWM0-1	x * 64000, SDS-PAGE	654435
?	Mus musculus	-	x * 63000, SDS-PAGE	690692
?	Ascaris suum	-	x * 66000, SDS-PAGE	690790
?	Homo sapiens	-	x * 62000, SDS-PAGE	691600
?	Homo sapiens	-	x * 61900, SMO/PAOh1, SDS-PAGE; x * 65000, SMO5, SDS-PAGE	692298
?	Mus musculus	-	x * 61852, calculated from sequence; x * 68000, secreted-tagged enzyme form, SDS-PAGE	692970
?	Arabidopsis thaliana	Q8H191	x * 55000, recombinant His-tagged AtPAO4, SDS-PAGE; x * 55000, SDS-PAGE	694651

POSTTRANSLATIONAL MODIFICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
flavoprotein	Arabidopsis thaliana	Q8H191	-	694651

Crystallization/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
molecular modeling of enzyme and enzyme-spermine complex. Spermine oxidase binds spermine in a similar conformation as that observed in the yeast polyamine oxidase FMS1-spermine complex, with a major role for residues H82 and K367 in substrate binding and catalysis. The enzyme�substrate complex shows an active site pocket with highly polar characteristics	Mus musculus	-	710832

pH STABILITY	pH STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE STABILITY	TEMPERATURE STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
30	-	Ascaris suum	-	complete loss of activity after 60 min	690790
37	-	Ascaris suum	-	complete loss of activity after 30 min	690790
42	-	Ascaris suum	-	complete loss of activity after 20 min	690790
56	-	Ascaris suum	-	complete loss of activity after 10 min	690790

GENERAL STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

ORGANIC SOLVENT	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

OXIDATION STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

STORAGE STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
-20�C, stable for 2 days minimal loss of activity, complete loss of enzyme activity after 14 days	Ascaris suum	-	690790

Purification/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
; recombinant His-tagged AtPAO4 from Escherichia coli strain BL21(DE3)	Arabidopsis thaliana	Q8H191	694651
recombinant protein	Arabidopsis thaliana	Q9FNA2	676604
-	Ascaris suum	-	690790
-	Homo sapiens	-	692978
recombinant enzyme	Homo sapiens	Q9NWM0-1	654435
recombinant enzyme, SMO5; recombinant enzyme, SMO/PAOh1	Homo sapiens	-	692298
-	Mus musculus	-	692970
recombinant enzyme	Mus musculus	-	673538, 690692
recombinantly expressed mSMO isoforms	Mus musculus	Q99K82	692157
recombinantly produced mSMOmuDELTA (with a deletion of the nuclear domain)	Mus musculus	-	692280

Cloned/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
AtPAO1 cDNA is isolated and cloned in a vector for heterologous expression in Escherichia coli	Arabidopsis thaliana	Q9FNA2	676604
expression in Escherichia coli as a His-tagged protein; expression of His-tagged AtPAO4 in Escherichia coli strain BL21(DE3), transient expression of isozyme AtPAO4 in Arabidopsis thaliana root cell peroxisomes as monomeric red fluorescent protein fusion protein	Arabidopsis thaliana	Q8H191	694651
-	Homo sapiens	-	691600
cDNA is transiently transfected into HEK-293 cells	Homo sapiens	-	690800
SMO5 cDNA is subcloned into the pET15b bacterial expression vector, expression in Escherichia coli. NCI-H157 human non-small cell lung carcinoma cells are stably transfected, and individual clones selected that overexpress the enzyme; SMO/PAOh1 cDNA is subcloned into the pET15b bacterial expression vector, expression in Escherichia coli. NCI-H157 human non-small cell lung carcinoma cells are stably transfected, and individual clones selected that overexpress the enzyme	Homo sapiens	-	692298
-	Mus musculus	-	711592
cDNA is transiently transfected into HEK-293 cells	Mus musculus	-	690800
expression in Escherichia coli	Mus musculus	-	673538
expression in Escherichia coli BL21 DE3	Mus musculus	-	690692
expression of mutant mSMOmuDELTA (with a deletion of the nuclear domain) in Escherichia coli	Mus musculus	-	692280
mSMO splice variants, expression in Escherichia coli and in in murine neuroblastoma N18TG2 cells	Mus musculus	Q99K82	692157
subcloned and expressed in secreted and secreted-tagged forms into Escherichia coli BL21 DE3 cells	Mus musculus	-	692970

EXPRESSION	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
both the expression level of SMO mRNA and SMO enzyme activity are significantly lower in breast cancer samples compared to nontumor samples	Homo sapiens	-	711592
SMO transcript accumulation and enzymatic activity increase during C2C12 cell differentiation and correlate with the decrease of spermine content	Mus musculus	-	692648

ENGINEERING	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
H82E	Mus musculus	-	no catalytic activity	710832
H82Q	Mus musculus	-	about 300fold decrease in catalytic efficiency	710832
T428Y	Mus musculus	-	no catalytic activity	710832
additional information	Arabidopsis thaliana	Q8H191	construction of a knock-out mutant that has a T-DNA insertion within the ninth exon of the AtPAO4 gene, and of a knock-down mutant Atpao4i with reduced expression by RNAi under control of the CMV 35S promoter. AtPAO4 deficiency induces alterations in the expression of genes related to the drought stress response and flavonoid biosynthesis	694651
K367M	Mus musculus	-	about 3fold decrease in catalytic efficiency	710832
additional information	Mus musculus	-	purified mutant mSMOmuDELTA (with a deletion of the nuclear domain A) exhibits biochemical properties very similar to that of mSMOalpha and mSMOmu, in particular a pH optimum of 8.5 in 0.1 m Na-phosphate buffer, a Km value of 0.222 mM and a kcat value of 0.0208 per sec. Removal of the nuclear domain amino acid region abolishes proper nuclear targeting of the mSMOmu isoform	692280

Renatured/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
protein is first purified from the cell lysate under denaturing conditions and renatured by dialysis against decreasing concentrations of urea	Homo sapiens	Q9NWM0-1	654435

APPLICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
medicine	Ascaris suum	-	the inhibitor MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections	694540
medicine	Homo sapiens	-	both the expression level of SMO mRNA and SMO enzyme activity are significantly lower in breast cancer samples compared to nontumor samples	711592
medicine	Homo sapiens	-	alterations in the levels of spermine synthase SMS and spermine oxidase SMOX have previously been observed in brains of suicide completers. SMS and SMOX display several promoter haplotypes, without consistent effects of haplotype on expression levels in either the brain or in reporter gene assays performed in three different cell lines. There are no overall effects of epigenetic factors in determining expression, with the exception of a relationship between CpG methylation at one site in the promoter of SMOX and its expression in Brodmann area 8/9. The genetic and epigenetic factors examined in this study show little influence on the expression levels of SMS and SMOX	712194
medicine	Homo sapiens	-	treatment of human C-28/I2 chondrocytes with polyamine analogue N1,N11-diethylnorspermine rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels	712558

DISEASE	TITLE OF PUBLICATION	LINK TO PUBMED
Adenocarcinoma	Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells.	PubMed
Breast Neoplasms	Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.	PubMed
Breast Neoplasms	Spermine oxidase SMO(PAOh1), Not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines.	PubMed
Carcinoma	Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells.	PubMed
Colitis, Ulcerative	Increased expression and cellular localization of spermine oxidase in ulcerative colitis and relationship to disease activity.	PubMed
Colorectal Neoplasms	Polyamine catabolism in colorectal cancer cells following treatment with oxaliplatin, 5-fluorouracil and N1, N11 diethylnorspermine.	PubMed
Diabetic Nephropathies	Polyamines in renal failure.	PubMed
Gastritis	Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis.	PubMed
Glomerulonephritis	Polyamines in renal failure.	PubMed
Hypersensitivity	Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure.	PubMed
Infection	Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis.	PubMed
Kidney Failure, Chronic	Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke.	PubMed
Kidney Failure, Chronic	Polyamines in renal failure.	PubMed
Lung Neoplasms	Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells.	PubMed
Neoplasms	Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues.	PubMed
Neoplasms	Induction of the PAOh1/SMO polyamine oxidase by polyamine analogues in human lung carcinoma cells.	PubMed
Neoplasms	Inflammation and polyamine catabolism: the good, the bad and the ugly.	PubMed
Neoplasms	The polyamine analog PG11047 potentiates the antitumor activity of cisplatin and bevacizumab in preclinical models of lung and prostate cancer.	PubMed
Neoplasms	Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis.	PubMed
Nephrosclerosis	Polyamines in renal failure.	PubMed
Neuroblastoma	Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure.	PubMed
Neuroblastoma	Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells.	PubMed
Neuroblastoma	Mouse spermine oxidase gene splice variants. Nuclear subcellular localization of a novel active isoform.	PubMed
Ovarian Neoplasms	Polyamine catabolism in platinum drug action: Interactions between oxaliplatin and the polyamine analogue N1,N11-diethylnorspermine at the level of spermidine/spermine N1-acetyltransferase.	PubMed
Pancreatitis	[Methylated analogues of spermine and spermidine as tools to investigate cellular functions of polyamines and the enzymes of their metabolism]	PubMed
Prostatic Intraepithelial Neoplasia	Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues.	PubMed
Prostatic Neoplasms	Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues.	PubMed
Reperfusion Injury	The Role of Spermidine/Spermine-N1-Acetyltransferase in Endotoxin-Induced Acute Kidney Injury.	PubMed
spermine oxidase deficiency	A putative peroxisomal polyamine oxidase, AtPAO4, is involved in polyamine catabolism in Arabidopsis thaliana.	PubMed
Stomach Neoplasms	Spermine Oxidase Mediates the Gastric Cancer Risk Associated With Helicobacter pylori CagA.	PubMed
Stomach Neoplasms	Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk.	PubMed
Stomach Neoplasms	Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis.	PubMed
Stroke	Acrolein, IL-6 and CRP as markers of silent brain infarction.	PubMed

REF.	AUTHORS	TITLE	JOURNAL	VOL.	PAGES	YEAR	ORGANISM	LINK TO PUBMED	SOURCE
654435	Wang, Y.; Murray-Stewart, T.; Devereux, W.; Hacker, A.; Frydman, B.; Woster, P.M.; Casero, R.A.Jr.	Properties of purified human polyamine oxidase, PAOh1/SMO	Biochem. Biophys. Res. Commun.	304	605-611	2003	Homo sapiens	PubMed
673538	Bianchi, M.; Polticelli, F.; Ascenzi, P.; Botta, M.; Federico, R.; Mariottini, P.; Cona, A.	Inhibition of polyamine and spermine oxidases by polyamine analogues	FEBS J.	273	1115-1123	2006	Mus musculus	PubMed
676604	Tavladoraki, P.; Rossi, M.N.; Saccuti, G.; Perez-Amador, M.A.; Polticelli, F.; Angelini, R.; Federico, R.	Heterologous expression and biochemical characterization of a polyamine oxidase from Arabidopsis involved in polyamine back conversion	Plant Physiol.	141	1519-1532	2006	Arabidopsis thaliana	PubMed
690692	Bellelli, A.; Cavallo, S.; Nicolini, L.; Cervelli, M.; Bianchi, M.; Mariottini, P.; Zelli, M.; Federico, R.	Mouse spermine oxidase: a model of the catalytic cycle and its inhibition by N,N1-bis(2,3-butadienyl)-1,4-butanediamine	Biochem. Biophys. Res. Commun.	322	1-8	2004	Mus musculus	PubMed
690790	M�ller, S.; Walter, R.D.	Purification and characterization of polyamine oxidase from Ascaris suum	Biochem. J.	1283	75-80	1992	Ascaris suum	PubMed
690800	Vujcic, S.; Diegelman, P.; Bacchi, C.J.; Kramer, D.L.; Porter, C.W.	Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin	Biochem. J.	367	665-675	2002	Homo sapiens, Mus musculus	PubMed
690802	Wang, Y.; Hacker, A.; Murray-Stewart, T.; Fleischer, J.G.; Woster, P.M.	Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein	Biochem. J.	386	543-547	2005	Homo sapiens	PubMed
691035	Amendolaa, R.; Bellini, A.; Cervelli, M.; Deganc, P.; Marcoccid, L.; Martinie, F.; Mariottini, P.	Direct oxidative DNA damage, apoptosis and radio sensitivity by spermine oxidase activities in mouse neuroblastoma cells	Biochim. Biophys. Acta	1755	15-24	2005	Mus musculus	PubMed
691051	Bianchi, M.; Bellini, A.; Cervelli, M.; Degan, P.; Narcocci, L.; Martini, F; Scatteia, M.; Mariottini, P.; Amendola, R.	Chronic sub-lethal oxidative stress by spermine oxidase overactivity induces continuous DNA repair and hypersensitivity to radiation exposure	Biochim. Biophys. Acta	1773	774-783	2007	Mus musculus	PubMed
691600	Wang, Y.; Devereux, W.; Woster, P.M.; Stewart, T.M.; Hacker, A.; Casero, R.A.	Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure.	Cancer Res.	61	5370-5373	2001	Homo sapiens	PubMed
691601	Babbar, N.; Casero, R.A.	Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis	Cancer Res.	66	11125-11130	2006	Homo sapiens	PubMed
692157	Cervelli, M.; Bellini, A.; Bianchi, M.; Marcocci, L.; Nocera, S.; Polticelli, F.; Federico, R.; Amendola, R.; Mariottini, P.	Mouse spermine oxidase gene splice variants. Nuclear subcellular localization of a novel active isoform	Eur. J. Biochem.	760	760-770	2004	Mus musculus	PubMed
692280	Bianchi, M.; Amendola, R.; Federico, R.; Polticelli, F.; Mariottin, P.	Two short protein domains are responsible for the nuclear localization of the mouse spermine oxidase mu isoform	FEBS J.	272	3052-3059	2005	Mus musculus	PubMed
692298	Murray-Stewart, T.; Wang, Y.; Goodwin, A.; Hacker A.; Meeker, A.; casero, R.A.	Nuclear localization of human spermine oxidase isoforms - possible implications in drug response and disease etiology	FEBS J.	275	2795-2806	2008	Homo sapiens	PubMed
692648	Cervelli, M.; Fratini, E.; Amendola, A.; Bianchi, M.; Signori, E.; Ferraro, E.; Lisi, A.; Federico, R.; Marcocci, L.; Mariottini, P.	Increased spermine oxidase (SMO) activity as a novel differentiation marker of myogenic C2C12 cells	Int. J. Biochem. Cell Biol.	41	934-944	2009	Mus musculus	PubMed
692970	Cervelli, M.; Polticelli, F.; Federico, R.; Mariottini, P.	Heterologous expression and characterization of mouse spermine oxidase	J. Biol. Chem.	278	5271-5276	2003	Mus musculus	PubMed
692977	Pledgie, A.; Huang, Y.; Hacker, A.; Zhang, Z.; Woster, P.M.; Davidson, N.E.; Casero, R.A.	Spermine oxidase SMO(PAOh1), not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines	J. Biol. Chem.	280	39843-39851	2005	Homo sapiens	PubMed
692978	J�rvinen, A.; Grigorenko, N.; Khomutov, A.R.; Hyv�nen, M.T.; Uimari, A.; Veps�l�inen, J.; Sinervirta, R.; Kein�nen, T.A.; Vujcic, S.; Alhonen, L.; Porter, C.W.; J�nne, J.	Metabolic stability of alpha-methylated polyamine derivatives and their use as substitutes for the natural polyamines.	J. Biol. Chem.	280	6595-6601	2005	Homo sapiens	PubMed
694540	M�ller, S.; Hunter, K.J.; Walter, R.D.	Effect of haloallylamines on polyamine oxidase activity and spermine levels in Ascaris suum	Parasitol. Res.	82	571-573	1996	Ascaris suum	PubMed
694651	Kamada-Nobusada, T.; Hayashi, M.; Fukazawa, M.; Sakakibara, H.; Nishimura, M.	A putative peroxisomal polyamine oxidase, AtPAO4, is involved in polyamine catabolism in Arabidopsis thaliana	Plant Cell Physiol.	49	1272-1282	2008	Arabidopsis thaliana	PubMed
694943	Goodwin, A.C.; Jadallah, S.; Toubaji, A.; Lecksell, K.; Hicks, J.L.; Kowalski, J.; Bova, G.S.; de Marzo, A.M.; Netto, G.J.; Casero, R.A.	Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues	Prostate	68	766-772	2008	Homo sapiens	PubMed
710832	Tavladoraki, P.; Cervelli, M.; Antonangeli, F.; Minervini, G.; Stano, P.; Federico, R.; Mariottini, P.; Polticelli, F.	Probing mammalian spermine oxidase enzyme-substrate complex through molecular modeling, site-directed mutagenesis and biochemical characterization	Amino Acids	40	1115-1126	2010	Mus musculus	PubMed
711241	Adachi, M.S.; Juarez, P.R.; Fitzpatrick, P.F.	Mechanistic studies of human spermine oxidase: kinetic mechanism and pH effects	Biochemistry	49	386-392	2010	Homo sapiens	PubMed
711592	Cervelli, M.; Bellavia, G.; Fratini, E.; Amendola, R.; Polticelli, F.; Barba, M.; Federico, R.; Signore, F.; Gucciardo, G.; Grillo, R.; Woster, P.; Casero Jr, R.; Mariottini, P.	Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm	BMC Cancer	10	555	2010	Homo sapiens, Mus musculus	PubMed
712194	Fiori, L.M.; Turecki, G.	Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers	Int. J. Neuropsychopharmacol.	13	725-736	2010	Homo sapiens	PubMed
712558	Stanic, I.; Facchini, A.; Borzi, R.; Stefanelli, C.; Flamigni, F.	The polyamine analogue N1,N11-diethylnorspermine can induce chondrocyte apoptosis independently of its ability to alter metabolism and levels of natural polyamines	J. Cell. Physiol.	219	109-116	2009	Homo sapiens	PubMed
712608	Fincato, P.; Moschou, P.N.; Spedaletti, V.; Tavazza, R.; Angelini, R.; Federico, R.; Roubelakis-Angelakis, K.A.; Tavladoraki, P.	Functional diversity inside the Arabidopsis polyamine oxidase gene family	J. Exp. Bot.	6	1155-1168	2010	Arabidopsis thaliana	PubMed
713263	Takahashi, Y.; Cong, R.; Sagor, G.H.; Niitsu, M.; Berberich, T.; Kusano, T.	Characterization of five polyamine oxidase isoforms in Arabidopsis thaliana	Plant Cell Rep.	29	955-965	2010	Arabidopsis thaliana	PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 1.5.3.16)

NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM

IUBMB Enzyme Nomenclature

PROSITE Database of protein families and domains

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Protein Mutant Database

InterPro (database of protein families, domains and functional sites)

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