Alternative titles; symbols
HGNC Approved Gene Symbol: SMOX
Cytogenetic location: 20p13 Genomic coordinates (GRCh38): 20:4,148,828-4,187,727 (from NCBI)
The natural polyamines, spermine, spermidine, and putrescine, are ubiquitous polycationic alkylamines that are required for normal cell growth and differentiation. SMOX catalyzes an oxidative step in polyamine catabolism (summary by Pledgie et al., 2005).
Using maize Pao (615853) to query a human database, Vujcic et al. (2002) identified SMOX, which they called SMO. The deduced 555-amino acid full-length protein has a calculated molecular mass of 61.8 kD. Vujcic et al. (2002) also identified 2 SMO splice variants.
By RT-PCR of total RNA from 2 human cell lines and PCR of a human placenta cDNA library, Murray-Stewart et al. (2002) cloned 4 SMOX splice variants, which they called PAOH1 through PAOH4. PAOH1 encodes the full-length 555-amino acid protein, whereas PAOH2, PAOH3, and PAOH4 encode 502-, 190-, and 532-amino acid proteins, respectively. Compared with the other isoforms, PAOH3 lacks an internal stretch predicted to bind the FAD cofactor.
By EST database analysis, Vujcic et al. (2003) found that SMOX was expressed in brain, eye, lung, placenta, prostate, and spleen, as well as in several neoplasias.
Using transfected HEK293 cells, Vujcic et al. (2002) showed that human SMO oxidized spermine to form spermidine. It did not use N(1)-acetylspermine or other related substrates tested. SMO showed highest activity at pH 9.5. Mouse Smo showed the same substrate preference as human SMO.
Using a wheat germ translational system to generate all 4 human PAOH isoforms, Murray-Stewart et al. (2002) found that each isoform had specific kinetics and affinities for the substrates spermine, spermidine, and N(1)-acetylspermine. The shortest isoform, PAOH3, had the highest specific activities for all 3 substrates.
The antitumor polyamine analog N(1),N(1)-bis(ethyl)norspermine (BENSpm) is cytotoxic due to induction of H2O2 formation. Pledgie et al. (2005) found that BENSpm induced SSAT (SAT1; 313020) and SMO mRNA and activities in multiple human breast cancer cell lines, in addition to inhibiting cell growth, reducing polyamine levels, and inhibiting ornithine decarboxylase (ODC1; 165640) activity. Knockdown of SSAT or SMO differentially reduced cellular responses to BENSpm depending on the cell line, and knockdown of both further reduced cell sensitivity. Knockdown of SMO, but not SSAT or PAOX, specifically reduced BENSpm-induced formation of reactive oxygen species. Pledgie et al. (2005) concluded that SMO is responsible for BENSpm-induced H2O2 production and cytotoxicity.
Vujcic et al. (2002) determined that the SMOX gene contains 8 exons.
Murray-Stewart et al. (2002) found that a central sequence in exon 5 of the SMOX gene is spliced out in 2 variants, which they called PAOH2 and PAOH4. PAOH4 contains an additional exon, exon 6a, that is absent in the other splice variants.
Vujcic et al. (2002) reported that the mouse and human SMOX genes map to chromosomes 2 and 20, respectively.
Hartz (2014) mapped the SMOX gene to chromosome 20p13 based on an alignment of the SMOX sequence (GenBank AK000753) with the genomic sequence (GRCh37).
Hartz, P. A. Personal Communication. Baltimore, Md. 6/20/2014.
Murray-Stewart, T., Wang, Y., Devereux, W., Casero, R. A., Jr. Cloning and characterization of multiple human polyamine oxidase splice variants that code for isoenzymes with different biochemical characteristics. Biochem. J. 368: 673-677, 2002. [PubMed: 12398765] [Full Text: https://doi.org/10.1042/BJ20021587]
Pledgie, A., Huang, Y., Hacker, A., Zhang, Z., Woster, P. M., Davidson, N. E., Casero, R. A., Jr. Spermine oxidase SMO(PAOh1), not N(1)-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. [PubMed: 16207710] [Full Text: https://doi.org/10.1074/jbc.M508177200]
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. [PubMed: 12141946] [Full Text: https://doi.org/10.1042/BJ20020720]
Vujcic, S., Liang, P., Diegelman, P., Kramer, D. L., Porter, C. W. Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion. Biochem. J. 370: 19-28, 2003. [PubMed: 12477380] [Full Text: https://doi.org/10.1042/BJ20021779]