SPSY_MOUSE
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 03-AUG-2022, entry version 174.
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 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 iPTMnet; P97355; -.
DR PhosphoSitePlus; P97355; -.
DR EPD; P97355; -.
DR MaxQB; P97355; -.
DR PaxDb; P97355; -.
DR PeptideAtlas; P97355; -.
DR PRIDE; P97355; -.
DR ProteomicsDB; 258732; -.
DR Antibodypedia; 24466; 389 antibodies from 27 providers.
DR DNASU; 20603; -.
DR Ensembl; ENSMUST00000112529; ENSMUSP00000108148; ENSMUSG00000071708.
DR GeneID; 20603; -.
DR KEGG; mmu:20603; -.
DR UCSC; uc033jve.1; mouse.
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; TIWKKQT; -.
DR OrthoDB; 1243182at2759; -.
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 73 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 269 other tissues.
DR ExpressionAtlas; P97355; baseline and differential.
DR Genevisible; P97355; MM.
DR GO; GO:0016768; F:spermine synthase activity; ISO:MGI.
DR GO; GO:0006597; P:spermine biosynthetic process; IBA:GO_Central.
DR GO; GO:0008215; P:spermine metabolic process; IMP:MGI.
DR Gene3D; 2.30.140.10; -; 1.
DR Gene3D; 3.40.50.150; -; 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; PTHR46315; 1.
DR Pfam; PF17284; Spermine_synt_N; 1.
DR Pfam; PF17950; SpmSyn_N; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS01330; PABS_1; 1.
DR PROSITE; PS51006; PABS_2; 1.
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
