ID SPSY_HUMAN Reviewed; 366 AA. AC P52788; A6NHA7; A6NI34; B2R9M0; O00544; Q9UQS1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Spermine synthase {ECO:0000303|PubMed:7546290}; DE Short=SPMSY; DE EC=2.5.1.22 {ECO:0000269|PubMed:18367445}; DE AltName: Full=Spermidine aminopropyltransferase; GN Name=SMS {ECO:0000303|PubMed:14508504, ECO:0000312|HGNC:HGNC:11123}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=7546290; DOI=10.1089/dna.1995.14.841; RA Korhonen V.-P., Halmekytoe M., Kauppinen L., Myoehaenen S., Wahlfors J., RA Keinaenen T., Hyvoenen T., Alhonen L., Eloranta T., Jaenne J.; RT "Molecular cloning of a cDNA encoding human spermine synthase."; RL DNA Cell Biol. 14:841-847(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=9299240; DOI=10.1006/geno.1997.4876; RA Grieff M., Whyte M.P., Thakker R.V., Mazzarella R.; RT "Sequence analysis of 139 kb in Xp22.1 containing spermine synthase and the RT 5' region of PEX."; RL Genomics 44:227-231(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney, and Skin; 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 [7] RP PARTIAL PROTEIN SEQUENCE. RA Eloranta T., Kajander O., Kauppinen L., Hyvoenen T., Linnala-Kankkunen A., RA Kalkkinen N., Kulomaa M., Alhonen L., Jaenne J.; RL (In) Goldemberg S.H., Algranati I.D. (eds.); RL Proceedings of the international symposium on the biology and chemistry of RL polyamines, pp.91-98, ICSU Press, New York (1988). RN [8] RP PROTEIN SEQUENCE OF 97-107 (ISOFORM 1). RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [9] RP INVOLVEMENT IN MRXSSR. RX PubMed=14508504; DOI=10.1038/sj.ejhg.5201072; RA Cason A.L., Ikeguchi Y., Skinner C., Wood T.C., Holden K.R., Lubs H.A., RA Martinez F., Simensen R.J., Stevenson R.E., Pegg A.E., Schwartz C.E.; RT "X-linked spermine synthase gene (SMS) defect: the first polyamine RT deficiency syndrome."; RL Eur. J. Hum. Genet. 11:937-944(2003). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 5-366 (ISOFORM 1) IN COMPLEX WITH RP SPERMIDINE AND 5-METHYLTHIOADENOSINE, FUNCTION, CATALYTIC ACTIVITY, RP SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF ASP-201; ASP-276 AND GLU-353. RX PubMed=18367445; DOI=10.1074/jbc.m710323200; RA Wu H., Min J., Zeng H., McCloskey D.E., Ikeguchi Y., Loppnau P., RA Michael A.J., Pegg A.E., Plotnikov A.N.; RT "Crystal structure of human spermine synthase: implications of substrate RT binding and catalytic mechanism."; RL J. Biol. Chem. 283:16135-16146(2008). RN [15] RP VARIANT MRXSSR SER-56, FUNCTION, INVOLVEMENT IN MRXSSR, AND RP CHARACTERIZATION OF VARIANT MRXSSR SER-56. RX PubMed=18550699; DOI=10.1136/jmg.2007.056713; RA de Alencastro G., McCloskey D.E., Kliemann S.E., Maranduba C.M., Pegg A.E., RA Wang X., Bertola D.R., Schwartz C.E., Passos-Bueno M.R., Sertie A.L.; RT "New SMS mutation leads to a striking reduction in spermine synthase RT protein function and a severe form of Snyder-Robinson X-linked recessive RT mental retardation syndrome."; RL J. Med. Genet. 45:539-543(2008). RN [16] RP VARIANT MRXSSR GLY-132, AND INVOLVEMENT IN MRXSSR. RX PubMed=19206178; DOI=10.1002/ajmg.a.32641; RA Becerra-Solano L.E., Butler J., Castaneda-Cisneros G., McCloskey D.E., RA Wang X., Pegg A.E., Schwartz C.E., Sanchez-Corona J., Garcia-Ortiz J.E.; RT "A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) RT causes Snyder-Robinson syndrome."; RL Am. J. Med. Genet. A 149A:328-335(2009). RN [17] RP VARIANT MRXSSR LEU-58. RX PubMed=22612257; DOI=10.1111/j.1528-1167.2012.03516.x; RA Lemke J.R., Riesch E., Scheurenbrand T., Schubach M., Wilhelm C., RA Steiner I., Hansen J., Courage C., Gallati S., Buerki S., Strozzi S., RA Simonetti B.G., Grunt S., Steinlin M., Alber M., Wolff M., Klopstock T., RA Prott E.C., Lorenz R., Spaich C., Rona S., Lakshminarasimhan M., Kroell J., RA Dorn T., Kraemer G., Synofzik M., Becker F., Weber Y.G., Lerche H., RA Boehm D., Biskup S.; RT "Targeted next generation sequencing as a diagnostic tool in epileptic RT disorders."; RL Epilepsia 53:1387-1398(2012). RN [18] RP VARIANT MRXSSR GLU-67, FUNCTION, AND CHARACTERIZATION OF VARIANT MRXSSR RP GLU-67. RX PubMed=23897707; DOI=10.1002/ajmg.a.36116; RA Peron A., Spaccini L., Norris J., Bova S.M., Selicorni A., Weber G., RA Wood T., Schwartz C.E., Mastrangelo M.; RT "Snyder-Robinson syndrome: a novel nonsense mutation in spermine synthase RT and expansion of the phenotype."; RL Am. J. Med. Genet. A 161A:2316-2320(2013). RN [19] RP ERRATUM OF PUBMED:23897707. RA Peron A., Spaccini L., Norris J., Bova S.M., Selicorni A., Weber G., RA Wood T., Schwartz C.E., Mastrangelo M.; RL Am. J. Med. Genet. A 161A:1083-1083(2014). RN [20] RP VARIANT MRXSSR CYS-328, FUNCTION, AND CHARACTERIZATION OF VARIANT MRXSSR RP CYS-328. RX PubMed=23696453; DOI=10.1093/hmg/ddt229; RA Zhang Z., Norris J., Kalscheuer V., Wood T., Wang L., Schwartz C., RA Alexov E., Van Esch H.; RT "A Y328C missense mutation in spermine synthase causes a mild form of RT Snyder-Robinson syndrome."; RL Hum. Mol. Genet. 22:3789-3797(2013). RN [21] RP VARIANT SER-60. RX PubMed=24680889; DOI=10.1016/j.ajhg.2014.03.006; RG UK10K Consortium; RA Grozeva D., Carss K., Spasic-Boskovic O., Parker M.J., Archer H., RA Firth H.V., Park S.M., Canham N., Holder S.E., Wilson M., Hackett A., RA Field M., Floyd J.A., Hurles M., Raymond F.L.; RT "De novo loss-of-function mutations in SETD5, encoding a methyltransferase RT in a 3p25 microdeletion syndrome critical region, cause intellectual RT disability."; RL Am. J. Hum. Genet. 94:618-624(2014). CC -!- FUNCTION: Catalyzes the production of spermine from spermidine and CC decarboxylated S-adenosylmethionine (dcSAM). CC {ECO:0000269|PubMed:18367445, ECO:0000269|PubMed:18550699, CC ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. 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:0000269|PubMed:18367445}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19974; CC Evidence={ECO:0000269|PubMed:18367445}; CC -!- PATHWAY: Amine and polyamine biosynthesis; spermine biosynthesis; CC spermine from spermidine: step 1/1. {ECO:0000269|PubMed:18367445}. 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:0000269|PubMed:18367445}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P52788-1; Sequence=Displayed; CC Name=2; CC IsoId=P52788-2; Sequence=VSP_034406; 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:0000269|PubMed:18367445}. CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic, CC Snyder-Robinson type (MRXSSR) [MIM:309583]: An X-linked intellectual CC disability syndrome characterized by a collection of clinical features CC including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis CC and unsteady gait. {ECO:0000269|PubMed:14508504, CC ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:19206178, CC ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23696453, CC ECO:0000269|PubMed:23897707}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the spermidine/spermine synthase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z49099; CAA88921.1; -; mRNA. DR EMBL; AD001528; AAB61308.1; -; mRNA. DR EMBL; AK313834; BAG36567.1; -; mRNA. DR EMBL; U53331; AAD08634.1; -; Genomic_DNA. DR EMBL; U73023; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471074; EAW98984.1; -; Genomic_DNA. DR EMBL; BC009898; AAH09898.1; -; mRNA. DR EMBL; BC085621; AAH85621.1; -; mRNA. DR CCDS; CCDS14203.1; -. [P52788-1] DR CCDS; CCDS59161.1; -. [P52788-2] DR PIR; S54160; S54160. DR RefSeq; NP_001245352.1; NM_001258423.1. [P52788-2] DR RefSeq; NP_004586.2; NM_004595.4. [P52788-1] DR PDB; 3C6K; X-ray; 1.95 A; A/B/C/D=5-366. DR PDB; 3C6M; X-ray; 2.45 A; A/B/C/D=5-366. DR PDBsum; 3C6K; -. DR PDBsum; 3C6M; -. DR AlphaFoldDB; P52788; -. DR SMR; P52788; -. DR BioGRID; 112495; 116. DR IntAct; P52788; 23. DR MINT; P52788; -. DR STRING; 9606.ENSP00000385746; -. DR BindingDB; P52788; -. DR ChEMBL; CHEMBL4934; -. DR DrugBank; DB00127; Spermine. DR GlyGen; P52788; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P52788; -. DR MetOSite; P52788; -. DR PhosphoSitePlus; P52788; -. DR SwissPalm; P52788; -. DR BioMuta; SMS; -. DR DMDM; 8247960; -. DR OGP; P52788; -. DR EPD; P52788; -. DR jPOST; P52788; -. DR MassIVE; P52788; -. DR MaxQB; P52788; -. DR PaxDb; 9606-ENSP00000385746; -. DR PeptideAtlas; P52788; -. DR ProteomicsDB; 56531; -. [P52788-1] DR ProteomicsDB; 56532; -. [P52788-2] DR Pumba; P52788; -. DR Antibodypedia; 24466; 449 antibodies from 27 providers. DR DNASU; 6611; -. DR Ensembl; ENST00000379404.5; ENSP00000368714.1; ENSG00000102172.16. [P52788-2] DR Ensembl; ENST00000404933.7; ENSP00000385746.2; ENSG00000102172.16. [P52788-1] DR GeneID; 6611; -. DR KEGG; hsa:6611; -. DR MANE-Select; ENST00000404933.7; ENSP00000385746.2; NM_004595.5; NP_004586.2. DR UCSC; uc004dag.5; human. [P52788-1] DR AGR; HGNC:11123; -. DR CTD; 6611; -. DR DisGeNET; 6611; -. DR GeneCards; SMS; -. DR GeneReviews; SMS; -. DR HGNC; HGNC:11123; SMS. DR HPA; ENSG00000102172; Low tissue specificity. DR MalaCards; SMS; -. DR MIM; 300105; gene. DR MIM; 309583; phenotype. DR neXtProt; NX_P52788; -. DR OpenTargets; ENSG00000102172; -. DR Orphanet; 3063; X-linked intellectual disability, Snyder type. DR PharmGKB; PA35972; -. DR VEuPathDB; HostDB:ENSG00000102172; -. DR eggNOG; KOG1562; Eukaryota. DR GeneTree; ENSGT00870000136506; -. DR HOGENOM; CLU_048650_1_0_1; -. DR InParanoid; P52788; -. DR OMA; YAGKEIC; -. DR OrthoDB; 3059359at2759; -. DR PhylomeDB; P52788; -. DR TreeFam; TF324508; -. DR BioCyc; MetaCyc:HS02362-MONOMER; -. DR BRENDA; 2.5.1.22; 2681. DR PathwayCommons; P52788; -. DR Reactome; R-HSA-351202; Metabolism of polyamines. DR SABIO-RK; P52788; -. DR SignaLink; P52788; -. DR UniPathway; UPA00249; UER00315. DR BioGRID-ORCS; 6611; 202 hits in 784 CRISPR screens. DR ChiTaRS; SMS; human. DR EvolutionaryTrace; P52788; -. DR GeneWiki; SMS_(gene); -. DR GenomeRNAi; 6611; -. DR Pharos; P52788; Tchem. DR PRO; PR:P52788; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P52788; Protein. DR Bgee; ENSG00000102172; Expressed in cortical plate and 100 other cell types or tissues. DR ExpressionAtlas; P52788; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016768; F:spermine synthase activity; IBA:GO_Central. DR GO; GO:0006555; P:methionine metabolic process; TAS:ProtInc. DR GO; GO:0006595; P:polyamine metabolic process; TAS:Reactome. DR GO; GO:0006597; P:spermine biosynthetic process; IBA:GO_Central. 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; P52788; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Intellectual disability; Phosphoprotein; Polyamine biosynthesis; KW Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..366 FT /note="Spermine synthase" FT /id="PRO_0000156538" 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 ECO:0000269|PubMed:18367445" FT BINDING 148 FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine" FT /ligand_id="ChEBI:CHEBI:57443" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 177 FT /ligand="spermidine" FT /ligand_id="ChEBI:CHEBI:57834" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 201 FT /ligand="spermidine" FT /ligand_id="ChEBI:CHEBI:57834" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 220 FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine" FT /ligand_id="ChEBI:CHEBI:57443" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 255..256 FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine" FT /ligand_id="ChEBI:CHEBI:57443" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 351 FT /ligand="spermidine" FT /ligand_id="ChEBI:CHEBI:57834" FT /evidence="ECO:0000269|PubMed:18367445" FT BINDING 353 FT /ligand="spermidine" FT /ligand_id="ChEBI:CHEBI:57834" FT /evidence="ECO:0000269|PubMed:18367445" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 57..109 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_034406" FT VARIANT 56 FT /note="G -> S (in MRXSSR; a reduced spermine/spermidine FT ratio is observed in patient lymphoblastoid cells FT consistent with impaired spermine biosynthesis; FT dbSNP:rs121434610)" FT /evidence="ECO:0000269|PubMed:18550699" FT /id="VAR_076449" FT VARIANT 58 FT /note="F -> L (in MRXSSR; dbSNP:rs397515549)" FT /evidence="ECO:0000269|PubMed:22612257" FT /id="VAR_072748" FT VARIANT 60 FT /note="N -> S (in dbSNP:rs1394834572)" FT /evidence="ECO:0000269|PubMed:24680889" FT /id="VAR_071048" FT VARIANT 67 FT /note="G -> E (in MRXSSR; a reduced spermine/spermidine FT ratio is observed in patient lymphoblastoid cells FT consistent with impaired spermine biosynthesis; FT dbSNP:rs397515550)" FT /evidence="ECO:0000269|PubMed:23897707" FT /id="VAR_076450" FT VARIANT 132 FT /note="V -> G (in MRXSSR; dbSNP:rs267607076)" FT /evidence="ECO:0000269|PubMed:19206178" FT /id="VAR_076451" FT VARIANT 328 FT /note="Y -> C (in MRXSSR; mild disease phenotype; a reduced FT spermine/spermidine ratio is observed in patient FT lymphoblastoid cells consistent with impaired spermine FT biosynthesis; dbSNP:rs397515553)" FT /evidence="ECO:0000269|PubMed:23696453" FT /id="VAR_076452" FT MUTAGEN 201 FT /note="D->A,N: 100,000-fold decrease in catalytic FT efficiency." FT /evidence="ECO:0000269|PubMed:18367445" FT MUTAGEN 276 FT /note="D->N: 200,000-fold decrease in catalytic FT efficiency." FT /evidence="ECO:0000269|PubMed:18367445" FT MUTAGEN 353 FT /note="E->Q: 800-fold decrease in catalytic efficiency." FT /evidence="ECO:0000269|PubMed:18367445" FT CONFLICT 1 FT /note="M -> MPG (in Ref. 1; CAA88921)" FT /evidence="ECO:0000305" FT STRAND 5..12 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 21..32 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 36..42 FT /evidence="ECO:0007829|PDB:3C6K" FT TURN 43..45 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 46..52 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 58..63 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 67..75 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 85..98 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 114..117 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 136..144 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 149..155 FT /evidence="ECO:0007829|PDB:3C6K" FT TURN 156..158 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 159..164 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 167..171 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 175..181 FT /evidence="ECO:0007829|PDB:3C6K" FT TURN 182..185 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 193..198 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 203..209 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 214..221 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 223..232 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 234..237 FT /evidence="ECO:0007829|PDB:3C6M" FT STRAND 242..246 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 249..254 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 256..266 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 270..276 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 291..304 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 306..318 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 322..332 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 339..346 FT /evidence="ECO:0007829|PDB:3C6K" FT HELIX 349..351 FT /evidence="ECO:0007829|PDB:3C6K" FT STRAND 355..362 FT /evidence="ECO:0007829|PDB:3C6K" SQ SEQUENCE 366 AA; 41268 MW; D5B23EF61DE66443 CRC64; MAAARHSTLD FMLGAKADGE TILKGLQSIF QEQGMAESVH TWQDHGYLAT YTNKNGSFAN LRIYPHGLVL LDLQSYDGDA QGKEEIDSIL NKVEERMKEL SQDSTGRVKR LPPIVRGGAI DRYWPTADGR LVEYDIDEVV YDEDSPYQNI KILHSKQFGN ILILSGDVNL AESDLAYTRA IMGSGKEDYT GKDVLILGGG DGGILCEIVK LKPKMVTMVE IDQMVIDGCK KYMRKTCGDV LDNLKGDCYQ VLIEDCIPVL KRYAKEGREF DYVINDLTAV PISTSPEEDS TWEFLRLILD LSMKVLKQDG KYFTQGNCVN LTEALSLYEE QLGRLYCPVE FSKEIVCVPS YLELWVFYTV WKKAKP //