ID   SPSY_MOUSE              Reviewed;         366 AA.
AC   P97355; A2AC82; Q3TL65; Q3TUP0; Q3UDT8; Q8C7P4; Q9CT09; Q9R282;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   27-MAR-2024, entry version 183.
DE   RecName: Full=Spermine synthase {ECO:0000303|PubMed:11160858};
DE            Short=SPMSY;
DE            EC=2.5.1.22 {ECO:0000250|UniProtKB:P52788};
DE   AltName: Full=Spermidine aminopropyltransferase {ECO:0000303|Ref.2};
GN   Name=Sms;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9063736; DOI=10.1093/hmg/6.2.165;
RA   Strom T.M., Francis F., Lorenz B., Boeddrich A., Econs M.J., Lehrach H.,
RA   Meitinger T.;
RT   "Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked
RT   hypophosphatemia.";
RL   Hum. Mol. Genet. 6:165-171(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Diaphragm;
RA   Niiranen K., Korhonen V., Janne J.;
RT   "Nucleotide sequence of mouse spermidine aminopropyltransferase cDNA.";
RL   Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RC   TISSUE=Bone marrow macrophage, Embryo, Embryonic spinal cord, and
RC   Morula;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Olfactory epithelium;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-315.
RC   STRAIN=129/SvJ;
RX   PubMed=11160858; DOI=10.1124/mol.59.2.231;
RA   Korhonen V.-P., Niiranen K., Halmekyto M., Pietila M., Diegelman P.,
RA   Parkkinen J.J., Eloranta T., Porter C.W., Alhonen L., Janne J.;
RT   "Spermine deficiency resulting from targeted disruption of the spermine
RT   synthase gene in embryonic stem cells leads to enhanced sensitivity to
RT   antiproliferative drugs.";
RL   Mol. Pharmacol. 59:231-238(2001).
RN   [7]
RP   PROTEIN SEQUENCE OF 297-307, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 316-366, FUNCTION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=9467015; DOI=10.1093/hmg/7.3.541;
RA   Lorenz B., Francis F., Gempel K., Boeddrich A., Josten M., Schmahl W.,
RA   Schmidt J., Lehrach H., Meitinger T., Strom T.M.;
RT   "Spermine deficiency in Gy mice caused by deletion of the spermine synthase
RT   gene.";
RL   Hum. Mol. Genet. 7:541-547(1998).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15459188; DOI=10.1074/jbc.m410471200;
RA   Wang X., Ikeguchi Y., McCloskey D.E., Nelson P., Pegg A.E.;
RT   "Spermine synthesis is required for normal viability, growth, and fertility
RT   in the mouse.";
RL   J. Biol. Chem. 279:51370-51375(2004).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the production of spermine from spermidine and
CC       decarboxylated S-adenosylmethionine (dcSAM) (PubMed:9467015). Required
CC       for normal viability, growth and fertility (PubMed:15459188).
CC       {ECO:0000269|PubMed:15459188, ECO:0000269|PubMed:9467015}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = H(+) +
CC         S-methyl-5'-thioadenosine + spermine; Xref=Rhea:RHEA:19973,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:45725,
CC         ChEBI:CHEBI:57443, ChEBI:CHEBI:57834; EC=2.5.1.22;
CC         Evidence={ECO:0000250|UniProtKB:P52788};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19974;
CC         Evidence={ECO:0000250|UniProtKB:P52788};
CC   -!- PATHWAY: Amine and polyamine biosynthesis; spermine biosynthesis;
CC       spermine from spermidine: step 1/1. {ECO:0000250|UniProtKB:P52788}.
CC   -!- SUBUNIT: Homodimer. Dimerization is mediated through the N-terminal
CC       domain and seems to be required for activity as deletion of the N-
CC       terminal domain causes complete loss of activity.
CC       {ECO:0000250|UniProtKB:P52788}.
CC   -!- DOMAIN: Composed of 3 domains: the N-terminal domain has structural
CC       similarity to S-adenosylmethionine decarboxylase, the central domain is
CC       made up of four beta strands and the C-terminal domain is similar in
CC       structure to spermidine synthase. The N- and C-terminal domains are
CC       both required for activity. {ECO:0000250|UniProtKB:P52788}.
CC   -!- DISRUPTION PHENOTYPE: Mouse ES cells lacking Sms display normal growth
CC       rates but are sensitive to antiproliferative and DNA damage-inducing
CC       drugs. {ECO:0000269|PubMed:15459188, ECO:0000269|PubMed:9467015}.
CC   -!- SIMILARITY: Belongs to the spermidine/spermine synthase family.
CC       {ECO:0000305}.
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DR   EMBL; Y09419; CAA70573.1; -; mRNA.
DR   EMBL; AF031486; AAB86631.1; -; mRNA.
DR   EMBL; AK049787; BAC33920.1; -; mRNA.
DR   EMBL; AK011542; BAB27685.1; -; mRNA.
DR   EMBL; AK017775; BAB30923.1; -; mRNA.
DR   EMBL; AK149929; BAE29173.1; -; mRNA.
DR   EMBL; AK160637; BAE35931.1; -; mRNA.
DR   EMBL; AK160659; BAE35947.1; -; mRNA.
DR   EMBL; AK166665; BAE38927.1; -; mRNA.
DR   EMBL; AL663072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC046623; AAH46623.1; -; mRNA.
DR   EMBL; BC058688; AAH58688.1; -; mRNA.
DR   EMBL; AF136179; AAD33057.1; -; Genomic_DNA.
DR   EMBL; AJ000093; CAA03919.1; -; Genomic_DNA.
DR   EMBL; AJ000087; CAA03918.1; -; Genomic_DNA.
DR   EMBL; AJ000088; CAA03918.1; JOINED; Genomic_DNA.
DR   EMBL; AJ000089; CAA03918.1; JOINED; Genomic_DNA.
DR   EMBL; AJ000090; CAA03918.1; JOINED; Genomic_DNA.
DR   EMBL; AJ000091; CAA03918.1; JOINED; Genomic_DNA.
DR   EMBL; AJ000092; CAA03918.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS41189.1; -.
DR   RefSeq; NP_033240.3; NM_009214.3.
DR   RefSeq; XP_001473484.1; XM_001473434.6.
DR   AlphaFoldDB; P97355; -.
DR   SMR; P97355; -.
DR   STRING; 10090.ENSMUSP00000108148; -.
DR   GlyGen; P97355; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P97355; -.
DR   PhosphoSitePlus; P97355; -.
DR   EPD; P97355; -.
DR   MaxQB; P97355; -.
DR   PaxDb; 10090-ENSMUSP00000108148; -.
DR   PeptideAtlas; P97355; -.
DR   ProteomicsDB; 258732; -.
DR   Pumba; P97355; -.
DR   Antibodypedia; 24466; 449 antibodies from 27 providers.
DR   DNASU; 20603; -.
DR   Ensembl; ENSMUST00000112529.8; ENSMUSP00000108148.2; ENSMUSG00000071708.12.
DR   GeneID; 20603; -.
DR   KEGG; mmu:20603; -.
DR   UCSC; uc033jve.1; mouse.
DR   AGR; MGI:109490; -.
DR   CTD; 6611; -.
DR   MGI; MGI:109490; Sms.
DR   VEuPathDB; HostDB:ENSMUSG00000071708; -.
DR   eggNOG; KOG1562; Eukaryota.
DR   GeneTree; ENSGT00870000136506; -.
DR   HOGENOM; CLU_048650_1_0_1; -.
DR   InParanoid; P97355; -.
DR   OMA; HTKGREE; -.
DR   OrthoDB; 3059359at2759; -.
DR   PhylomeDB; P97355; -.
DR   TreeFam; TF324508; -.
DR   Reactome; R-MMU-351202; Metabolism of polyamines.
DR   UniPathway; UPA00249; UER00315.
DR   BioGRID-ORCS; 20603; 5 hits in 78 CRISPR screens.
DR   BioGRID-ORCS; 671878; 0 hits in 1 CRISPR screen.
DR   ChiTaRS; Sms; mouse.
DR   PRO; PR:P97355; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; P97355; Protein.
DR   Bgee; ENSMUSG00000071708; Expressed in motor neuron and 271 other cell types or tissues.
DR   ExpressionAtlas; P97355; baseline and differential.
DR   GO; GO:0016768; F:spermine synthase activity; ISO:MGI.
DR   GO; GO:0006597; P:spermine biosynthetic process; ISO:MGI.
DR   GO; GO:0008215; P:spermine metabolic process; IMP:MGI.
DR   CDD; cd02440; AdoMet_MTases; 1.
DR   Gene3D; 2.30.140.10; Spermidine synthase, tetramerisation domain; 1.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR   InterPro; IPR030374; PABS.
DR   InterPro; IPR030373; PABS_CS.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR035246; Spermidine_synt_N.
DR   InterPro; IPR037163; Spermidine_synt_N_sf.
DR   InterPro; IPR015576; Spermine_synthase_animal.
DR   InterPro; IPR040900; SpmSyn_N.
DR   PANTHER; PTHR46315; SPERMINE SYNTHASE; 1.
DR   PANTHER; PTHR46315:SF1; SPERMINE SYNTHASE; 1.
DR   Pfam; PF17284; Spermine_synt_N; 1.
DR   Pfam; PF01564; Spermine_synth; 1.
DR   Pfam; PF17950; SpmSyn_N; 1.
DR   SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR   PROSITE; PS01330; PABS_1; 1.
DR   PROSITE; PS51006; PABS_2; 1.
DR   Genevisible; P97355; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Direct protein sequencing; Phosphoprotein;
KW   Polyamine biosynthesis; Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   CHAIN           2..366
FT                   /note="Spermine synthase"
FT                   /id="PRO_0000156539"
FT   DOMAIN          122..362
FT                   /note="PABS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00354"
FT   ACT_SITE        276
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00354"
FT   BINDING         148
FT                   /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT                   /ligand_id="ChEBI:CHEBI:57443"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         177
FT                   /ligand="spermidine"
FT                   /ligand_id="ChEBI:CHEBI:57834"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         201
FT                   /ligand="spermidine"
FT                   /ligand_id="ChEBI:CHEBI:57834"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         220
FT                   /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT                   /ligand_id="ChEBI:CHEBI:57443"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         255..256
FT                   /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT                   /ligand_id="ChEBI:CHEBI:57443"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         351
FT                   /ligand="spermidine"
FT                   /ligand_id="ChEBI:CHEBI:57834"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   BINDING         353
FT                   /ligand="spermidine"
FT                   /ligand_id="ChEBI:CHEBI:57834"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   MOD_RES         57
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52788"
FT   CONFLICT        188
FT                   /note="D -> H (in Ref. 3; BAC33920)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        245
FT                   /note="R -> K (in Ref. 3; BAC33920)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   366 AA;  41313 MW;  D549F319F51C43C5 CRC64;
     MAAARHSTLD FKLGAKADGE AILKGLQSIF QEQGMTESVH TWQDHGYLAT YTNKNGSFAN
     LRIYPHGLVL LDLQSYDSDV QGKQETDSLL NKIEEKMKEL SQDSTGRVKR LPPIVRGGAI
     DRYWPTADGR LVEYDIDEVV YDEDSPYQNI KILHSKQFGN ILILSGDVNL AESDLAYTRA
     IMGSGKEDYT GKDVLILGGG DGGILCEIVK LKPKMVTMVE IDQMVIDGCK KYMRRTCGDV
     LDNLRGDCYQ VLIEDCIPVL KMYAKEGREF DYVINDLTAV PISTSPEEDS TWDFLRLILD
     LSMKVLKQDG KYFTQGNCVN LTEALSLYEE QLGRLYCPVE FSKEIVCVPS YLELWVFYTV
     WKKAKP
//