SPSY_HUMAN
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 03-AUG-2022, entry version 192.
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}.
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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; 57.
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; P52788; -.
DR PeptideAtlas; P52788; -.
DR PRIDE; P52788; -.
DR ProteomicsDB; 56531; -. [P52788-1]
DR ProteomicsDB; 56532; -. [P52788-2]
DR Antibodypedia; 24466; 389 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 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; TIWKKQT; -.
DR OrthoDB; 1243182at2759; -.
DR PhylomeDB; P52788; -.
DR TreeFam; TF324508; -.
DR BioCyc; MetaCyc:HS02362-MON; -.
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; 183 hits in 701 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 99 other tissues.
DR ExpressionAtlas; P52788; baseline and differential.
DR Genevisible; P52788; HS.
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 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 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
