Full text data of SMS
SMS
[Confidence: low (only semi-automatic identification from reviews)]
Spermine synthase; SPMSY; 2.5.1.22 (Spermidine aminopropyltransferase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Spermine synthase; SPMSY; 2.5.1.22 (Spermidine aminopropyltransferase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P52788
ID SPSY_HUMAN Reviewed; 366 AA.
AC P52788; A6NHA7; A6NI34; B2R9M0; O00544; Q9UQS1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Spermine synthase;
DE Short=SPMSY;
DE EC=2.5.1.22;
DE AltName: Full=Spermidine aminopropyltransferase;
GN Name=SMS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Wahlfors J., Keinaenen T., Hyvoenen T., Alhonen L., Eloranta T.,
RA 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
RT and the 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Linnala-Kankkunen A., 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
RL chemistry of 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric 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.,
RA Lubs H.A., Martinez F., Simensen R.J., Stevenson R.E., Pegg A.E.,
RA 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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 5-366 (ISOFORM 1) IN COMPLEX
RP WITH SPERMIDINE AND 5-METHYLTHIOADENOSINE, SUBUNIT, AND MUTAGENESIS OF
RP 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
RT substrate binding and catalytic mechanism.";
RL J. Biol. Chem. 283:16135-16146(2008).
CC -!- FUNCTION: Catalyzes the production of spermine from spermidine and
CC decarboxylated S-adenosylmethionine (dcSAM).
CC -!- CATALYTIC ACTIVITY: S-adenosyl 3-(methylthio)propylamine +
CC spermidine = S-methyl-5'-thioadenosine + spermine.
CC -!- PATHWAY: Amine and polyamine biosynthesis; spermine biosynthesis;
CC spermine from spermidine: step 1/1.
CC -!- SUBUNIT: Homodimer. Dimerization is mediated through the N-
CC terminal domain and seems to be required for activity as deletion
CC of the N-terminal domain causes complete loss of activity.
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 Note=Gene prediction confirmed by EST data;
CC -!- DOMAIN: Composed of 3 domains: the N-terminal domain has
CC structural similarity to S-adenosylmethionine decarboxylase, the
CC central domain is made up of four beta strands and the C-terminal
CC domain is similar in structure to spermidine synthase. The N- and
CC C-terminal domains are both required for activity.
CC -!- DISEASE: X-linked syndromic mental retardation Snyder-Robinson
CC type (MRXSSR) [MIM:309583]: Characterized by moderate intellectual
CC deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis
CC and facial asymmetry. Transmission is X-linked recessive. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the spermidine/spermine synthase family.
CC -!- SIMILARITY: Contains 1 PABS (polyamine biosynthesis) domain.
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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 PIR; S54160; S54160.
DR RefSeq; NP_001245352.1; NM_001258423.1.
DR RefSeq; NP_004586.2; NM_004595.4.
DR UniGene; Hs.724874; -.
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 ProteinModelPortal; P52788; -.
DR SMR; P52788; 3-365.
DR IntAct; P52788; 6.
DR MINT; MINT-5002620; -.
DR STRING; 9606.ENSP00000385746; -.
DR BindingDB; P52788; -.
DR ChEMBL; CHEMBL4934; -.
DR DrugBank; DB00127; Spermine.
DR PhosphoSite; P52788; -.
DR DMDM; 8247960; -.
DR OGP; P52788; -.
DR PaxDb; P52788; -.
DR PRIDE; P52788; -.
DR DNASU; 6611; -.
DR Ensembl; ENST00000379404; ENSP00000368714; ENSG00000102172.
DR Ensembl; ENST00000404933; ENSP00000385746; ENSG00000102172.
DR GeneID; 6611; -.
DR KEGG; hsa:6611; -.
DR UCSC; uc004dag.4; human.
DR CTD; 6611; -.
DR GeneCards; GC0XP021958; -.
DR HGNC; HGNC:11123; SMS.
DR HPA; HPA029849; -.
DR HPA; HPA029852; -.
DR MIM; 300105; gene.
DR MIM; 309583; phenotype.
DR neXtProt; NX_P52788; -.
DR Orphanet; 3063; Intellectual deficit, X-linked, Snyder type.
DR PharmGKB; PA35972; -.
DR eggNOG; NOG259013; -.
DR HOGENOM; HOG000007053; -.
DR HOVERGEN; HBG004512; -.
DR InParanoid; P52788; -.
DR KO; K00802; -.
DR OMA; ARHSTLD; -.
DR OrthoDB; EOG7G1V6F; -.
DR PhylomeDB; P52788; -.
DR BioCyc; MetaCyc:HS02362-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P52788; -.
DR UniPathway; UPA00249; UER00315.
DR EvolutionaryTrace; P52788; -.
DR GeneWiki; SMS_(gene); -.
DR GenomeRNAi; 6611; -.
DR NextBio; 25739; -.
DR PRO; PR:P52788; -.
DR ArrayExpress; P52788; -.
DR Bgee; P52788; -.
DR CleanEx; HS_SMS; -.
DR Genevestigator; P52788; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004766; F:spermidine synthase activity; TAS:ProtInc.
DR GO; GO:0016768; F:spermine synthase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-UniPathway.
DR InterPro; IPR001045; Spermidine/spermine_synthase.
DR InterPro; IPR015576; Spermine_synthase.
DR PANTHER; PTHR11558; PTHR11558; 1.
DR PANTHER; PTHR11558:SF1; PTHR11558:SF1; 1.
DR Pfam; PF01564; Spermine_synth; 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; Complete proteome;
KW Direct protein sequencing; Mental retardation; Polyamine biosynthesis;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 366 Spermine synthase.
FT /FTId=PRO_0000156538.
FT DOMAIN 122 362 PABS.
FT REGION 255 256 S-adenosylmethioninamine binding.
FT ACT_SITE 276 276 Proton acceptor (By similarity).
FT BINDING 148 148 S-adenosylmethioninamine.
FT BINDING 177 177 Spermidine.
FT BINDING 201 201 Spermidine.
FT BINDING 220 220 S-adenosylmethioninamine.
FT BINDING 351 351 Spermidine.
FT BINDING 353 353 Spermidine.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 57 109 Missing (in isoform 2).
FT /FTId=VSP_034406.
FT MUTAGEN 201 201 D->A,N: 100,000-fold decrease in
FT catalytic efficiency.
FT MUTAGEN 276 276 D->N: 200,000-fold decrease in catalytic
FT efficiency.
FT MUTAGEN 353 353 E->Q: 800-fold decrease in catalytic
FT efficiency.
FT CONFLICT 1 1 M -> MPG (in Ref. 1; CAA88921).
FT STRAND 5 12
FT HELIX 21 32
FT STRAND 36 42
FT TURN 43 45
FT STRAND 46 52
FT STRAND 58 63
FT STRAND 67 75
FT HELIX 85 98
FT STRAND 114 117
FT STRAND 136 144
FT STRAND 149 155
FT TURN 156 158
FT STRAND 159 164
FT STRAND 167 171
FT HELIX 175 181
FT TURN 182 185
FT STRAND 193 198
FT HELIX 203 209
FT STRAND 214 221
FT HELIX 223 232
FT HELIX 234 237
FT STRAND 242 246
FT STRAND 249 254
FT HELIX 256 266
FT STRAND 270 276
FT HELIX 291 304
FT STRAND 306 318
FT HELIX 322 332
FT STRAND 335 337
FT STRAND 339 346
FT HELIX 349 351
FT STRAND 355 362
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
//
ID SPSY_HUMAN Reviewed; 366 AA.
AC P52788; A6NHA7; A6NI34; B2R9M0; O00544; Q9UQS1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-MAY-2000, sequence version 2.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Spermine synthase;
DE Short=SPMSY;
DE EC=2.5.1.22;
DE AltName: Full=Spermidine aminopropyltransferase;
GN Name=SMS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Wahlfors J., Keinaenen T., Hyvoenen T., Alhonen L., Eloranta T.,
RA 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
RT and the 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Linnala-Kankkunen A., 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
RL chemistry of 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.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric 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.,
RA Lubs H.A., Martinez F., Simensen R.J., Stevenson R.E., Pegg A.E.,
RA 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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a 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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 5-366 (ISOFORM 1) IN COMPLEX
RP WITH SPERMIDINE AND 5-METHYLTHIOADENOSINE, SUBUNIT, AND MUTAGENESIS OF
RP 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
RT substrate binding and catalytic mechanism.";
RL J. Biol. Chem. 283:16135-16146(2008).
CC -!- FUNCTION: Catalyzes the production of spermine from spermidine and
CC decarboxylated S-adenosylmethionine (dcSAM).
CC -!- CATALYTIC ACTIVITY: S-adenosyl 3-(methylthio)propylamine +
CC spermidine = S-methyl-5'-thioadenosine + spermine.
CC -!- PATHWAY: Amine and polyamine biosynthesis; spermine biosynthesis;
CC spermine from spermidine: step 1/1.
CC -!- SUBUNIT: Homodimer. Dimerization is mediated through the N-
CC terminal domain and seems to be required for activity as deletion
CC of the N-terminal domain causes complete loss of activity.
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 Note=Gene prediction confirmed by EST data;
CC -!- DOMAIN: Composed of 3 domains: the N-terminal domain has
CC structural similarity to S-adenosylmethionine decarboxylase, the
CC central domain is made up of four beta strands and the C-terminal
CC domain is similar in structure to spermidine synthase. The N- and
CC C-terminal domains are both required for activity.
CC -!- DISEASE: X-linked syndromic mental retardation Snyder-Robinson
CC type (MRXSSR) [MIM:309583]: Characterized by moderate intellectual
CC deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis
CC and facial asymmetry. Transmission is X-linked recessive. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the spermidine/spermine synthase family.
CC -!- SIMILARITY: Contains 1 PABS (polyamine biosynthesis) domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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 PIR; S54160; S54160.
DR RefSeq; NP_001245352.1; NM_001258423.1.
DR RefSeq; NP_004586.2; NM_004595.4.
DR UniGene; Hs.724874; -.
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 ProteinModelPortal; P52788; -.
DR SMR; P52788; 3-365.
DR IntAct; P52788; 6.
DR MINT; MINT-5002620; -.
DR STRING; 9606.ENSP00000385746; -.
DR BindingDB; P52788; -.
DR ChEMBL; CHEMBL4934; -.
DR DrugBank; DB00127; Spermine.
DR PhosphoSite; P52788; -.
DR DMDM; 8247960; -.
DR OGP; P52788; -.
DR PaxDb; P52788; -.
DR PRIDE; P52788; -.
DR DNASU; 6611; -.
DR Ensembl; ENST00000379404; ENSP00000368714; ENSG00000102172.
DR Ensembl; ENST00000404933; ENSP00000385746; ENSG00000102172.
DR GeneID; 6611; -.
DR KEGG; hsa:6611; -.
DR UCSC; uc004dag.4; human.
DR CTD; 6611; -.
DR GeneCards; GC0XP021958; -.
DR HGNC; HGNC:11123; SMS.
DR HPA; HPA029849; -.
DR HPA; HPA029852; -.
DR MIM; 300105; gene.
DR MIM; 309583; phenotype.
DR neXtProt; NX_P52788; -.
DR Orphanet; 3063; Intellectual deficit, X-linked, Snyder type.
DR PharmGKB; PA35972; -.
DR eggNOG; NOG259013; -.
DR HOGENOM; HOG000007053; -.
DR HOVERGEN; HBG004512; -.
DR InParanoid; P52788; -.
DR KO; K00802; -.
DR OMA; ARHSTLD; -.
DR OrthoDB; EOG7G1V6F; -.
DR PhylomeDB; P52788; -.
DR BioCyc; MetaCyc:HS02362-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P52788; -.
DR UniPathway; UPA00249; UER00315.
DR EvolutionaryTrace; P52788; -.
DR GeneWiki; SMS_(gene); -.
DR GenomeRNAi; 6611; -.
DR NextBio; 25739; -.
DR PRO; PR:P52788; -.
DR ArrayExpress; P52788; -.
DR Bgee; P52788; -.
DR CleanEx; HS_SMS; -.
DR Genevestigator; P52788; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004766; F:spermidine synthase activity; TAS:ProtInc.
DR GO; GO:0016768; F:spermine synthase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-UniPathway.
DR InterPro; IPR001045; Spermidine/spermine_synthase.
DR InterPro; IPR015576; Spermine_synthase.
DR PANTHER; PTHR11558; PTHR11558; 1.
DR PANTHER; PTHR11558:SF1; PTHR11558:SF1; 1.
DR Pfam; PF01564; Spermine_synth; 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; Complete proteome;
KW Direct protein sequencing; Mental retardation; Polyamine biosynthesis;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 366 Spermine synthase.
FT /FTId=PRO_0000156538.
FT DOMAIN 122 362 PABS.
FT REGION 255 256 S-adenosylmethioninamine binding.
FT ACT_SITE 276 276 Proton acceptor (By similarity).
FT BINDING 148 148 S-adenosylmethioninamine.
FT BINDING 177 177 Spermidine.
FT BINDING 201 201 Spermidine.
FT BINDING 220 220 S-adenosylmethioninamine.
FT BINDING 351 351 Spermidine.
FT BINDING 353 353 Spermidine.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 57 109 Missing (in isoform 2).
FT /FTId=VSP_034406.
FT MUTAGEN 201 201 D->A,N: 100,000-fold decrease in
FT catalytic efficiency.
FT MUTAGEN 276 276 D->N: 200,000-fold decrease in catalytic
FT efficiency.
FT MUTAGEN 353 353 E->Q: 800-fold decrease in catalytic
FT efficiency.
FT CONFLICT 1 1 M -> MPG (in Ref. 1; CAA88921).
FT STRAND 5 12
FT HELIX 21 32
FT STRAND 36 42
FT TURN 43 45
FT STRAND 46 52
FT STRAND 58 63
FT STRAND 67 75
FT HELIX 85 98
FT STRAND 114 117
FT STRAND 136 144
FT STRAND 149 155
FT TURN 156 158
FT STRAND 159 164
FT STRAND 167 171
FT HELIX 175 181
FT TURN 182 185
FT STRAND 193 198
FT HELIX 203 209
FT STRAND 214 221
FT HELIX 223 232
FT HELIX 234 237
FT STRAND 242 246
FT STRAND 249 254
FT HELIX 256 266
FT STRAND 270 276
FT HELIX 291 304
FT STRAND 306 318
FT HELIX 322 332
FT STRAND 335 337
FT STRAND 339 346
FT HELIX 349 351
FT STRAND 355 362
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
//
MIM
300105
*RECORD*
*FIELD* NO
300105
*FIELD* TI
*300105 SPERMINE SYNTHASE; SMS
*FIELD* TX
DESCRIPTION
Spermine synthase (EC 2.5.1.22) is 1 of 4 enzymes involved in the
read moresynthesis of polyamines from arginine and methionine. The others are
ornithine decarboxylase (165640), S-adenosyl-L-methionine decarboxylase
(180980), and spermidine synthase (182891).
CLONING
Korhonen et al. (1995) isolated and sequenced cDNA clones encoding human
spermine synthase. The open reading frame encodes a 368-amino acid
protein with little sequence similarity to proteins from bacterial and
mammalian sources catalyzing almost identical reactions.
GENE STRUCTURE
Grieff et al. (1997) determined that the SMS gene (which they symbolized
SpS) contains 11 exons spanning 54 kb.
MAPPING
Grieff et al. (1997) mapped the SMS gene 38 kb telomeric to the PHEX
gene (300550) on Xp22.1.
BIOCHEMICAL FEATURES
- Crystal Structure
Wu et al. (2008) determined the crystal structure of human SMS, which is
a dimer of 2 identical subunits. Each monomer has 3 domains: a
C-terminal domain, which contains the active site and is similar in
structure to spermidine synthase; a central domain made up of 4
beta-strands; and an N-terminal domain with structural similarity to
S-adenosylmethionine decarboxylase (AMD1; 180980), the enzyme that forms
the aminopropyl donor substrate. Dimerization occurs mainly through
interactions between the N-terminal domains. Deletion of the N-terminal
domain led to a complete loss of spermine synthase activity, suggesting
that dimerization may be required for activity.
MOLECULAR GENETICS
In affected members of a family with Snyder-Robinson mental retardation
syndrome (MRXSSR; 309583) originally reported by Snyder and Robinson
(1969), Cason et al. (2003) identified a splice site mutation in the SMS
gene (300105.0001).
In 2 Mexican brothers with MRXSSR, Becerra-Solano et al. (2009)
identified a mutation in the SMS gene (V132G; 300105.0003).
In 2 affected males from a Belgian family with a relatively mild form of
Snyder-Robinson mental retardation syndrome, Zhang et al. (2013)
identified a missense mutation in the SMS gene (Y328C; 300105.0004).
In a boy from Italy with Snyder-Robinson syndrome, Peron et al. (2013)
identified a nonsense mutation in the SMS gene (G67X; 300105.0005).
ANIMAL MODEL
First identified as a mouse model for X-linked hypophosphatemia, the
'Gyro' or 'Gy' mouse (see 300550) also exhibits neurologic
abnormalities, including deafness, hyperactivity, circling behavior, and
inner ear abnormalities (Lyon et al., 1986). Meyer et al. (1998) found
that the Gyro mouse has a partial deletion of both the Sms gene and the
Phex gene, making it a contiguous gene syndrome in that species.
However, as mutation in the Phex gene alone results in a
hypophosphatemic phenotype in the mouse (Hyp) without neurologic
manifestations, Meyer et al. (1998) suggested that a deficiency of
spermine may explain the additional neurologic findings in the Gy mouse.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, IVS4AS, G-A, +5
In affected members of a family with Snyder-Robinson mental retardation
syndrome (309583) originally reported by Snyder and Robinson (1969),
Cason et al. (2003) identified a G-to-A transition at position +5 of the
5-prime splice site of intron 4 of the SMS gene. The mutation segregated
with affected status in the family. Functional studies showed that the
mutation reduced the activity of SMS to 5% of controls. Cason et al.
(2003) noted that the deficiency of spermine in affected patients
suggested a role for polyamines in brain development and cognitive
function. The authors suggested cerebellar dysfunction or defective
functioning of neurons in the red nucleus.
.0002
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, GLY56SER
In affected male members of a Brazilian kindred with Snyder-Robinson
mental retardation syndrome (309583), de Alencastro et al. (2008)
identified a 267G-A transition in exon 2 of the SMS gene, resulting in a
gly56-to-ser (G56S) substitution in the N terminus. The phenotype was
severe, with profound mental retardation and epilepsy. The G56S mutation
segregated with the disease in this family and was not identified in 724
control X chromosomes. Female carriers in the family showed skewed X
inactivation. Patient cell lines showed no detectable SMS enzyme
activity and an increase in spermadine/spermine ratio.
.0003
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, VAL132GLY
In 2 Mexican brothers with Synder-Robinson mental retardation syndrome
(309583), Becerra-Solano et al. (2009) identified a 496T-G transversion
in exon 5 of the SMS gene, resulting in a val132-to-gly (V132G)
substitution in a highly conserved residue between the N-terminal domain
and the linker domain prior to the C-terminal domain that contains the
active site of the enzyme. The mutation was not found in 549 control
chromosomes. Spermine protein and activity were significantly decreased
in both patients but normal in their unaffected mother. The patients had
characteristic features of the disorder, including mental retardation,
osteoporosis, multiple fractures, and facial asymmetry.
.0004
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, TYR328CYS
In 2 affected males from a Belgian family with a relatively mild form of
Snyder-Robinson mental retardation syndrome (309583), Zhang et al.
(2013) identified a c.1084A-G transition in the SMS gene, resulting in a
tyr328-to-cys (Y328C) substitution. The mutation was also present in the
unaffected carrier mother. Biochemical studies showed that the mutant
protein could form a dimer, but there was significantly decreased SMS
activity and a reduction of protein levels to 20% of normal.
Transfection of the mutant protein into PC12 neuronal cells showed that
the Y328C mutation did not result in significantly decreased neurite
length compared to wildtype, and did not cause changes as severe as a
loss-of-function mutation (e.g., 300105.0001). However, molecular
modeling suggested that the Y328C mutations may increase conformational
dynamics of the protein, resulting in destabilization and a loss of
catalytic activity.
.0005
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, GLY67TER
In a boy with Snyder-Robinson syndrome (309583), Peron et al. (2013)
identified a c.200G-A transition in exon 3 of the SMS gene, resulting in
a gly67-to-ter (G67X) substitution. No spermine synthase activity above
baseline was detected in the patient's lymphoblastoid cells. The
patient's mother was heterozygous for the mutation and X-inactivation
analysis showed mild skewing. In addition to features characteristic of
Snyder-Robinson syndrome, the patient also had an ectopic kidney and
early-onset epilepsy.
*FIELD* RF
1. Becerra-Solano, L. E.; Butler, J.; Castaneda-Cisneros, G.; McCloskey,
D. E.; Wang, X.; Pegg, A. E.; Schwartz, C. E.; Sanchez-Corona, J.;
Garcia-Ortiz, J. E.: A missense mutation, p.V132G, in the X-linked
spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am.
J. Med. Genet. 149A: 328-335, 2009.
2. Cason, A. L.; Ikeguchi, Y.; Skinner, C.; Wood, T. C.; Holden, K.
R.; Lubs, H. A.; Martinez, F.; Simensen, R. J.; Stevenson, R. E.;
Pegg, A. E.; Schwartz, C. E.: X-linked spermine synthase gene (SMS)
defect: the first polyamine deficiency syndrome. Europ. J. Hum. Genet. 11:
937-944, 2003.
3. de Alencastro, G.; McCloskey, D. E.; Kliemann, S. E.; Maranduba,
C. M. C.; Pegg, A. E.; Wang, X.; Bertola, D. A.; Schwartz, C. E.;
Passos-Bueno, M. R.; Sertie, A. L.: New SMS mutation leads to a striking
reduction in spermine synthase protein function and a severe form
of Snyder-Robinson X-linked recessive mental retardation syndrome.
(Letter) J. Med. Genet. 45: 539-543, 2008.
4. Grieff, M.; Whyte, M. P.; Thakker, R. V.; Mazzarella, R.: Sequence
analysis of 139 kb in Xp22.1 containing spermine synthase and the
5-prime region of PEX. Genomics 44: 227-231, 1997.
5. Korhonen, V. P.; Halmekyto, M.; Kauppinen, L.; Myohanen, S.; Wahlfors,
J.; Keinanen, T.; Hyvonen, T.; Alhonen, L.; Eloranta, T.; Janne, J.
: Molecular cloning of a cDNA encoding human spermine synthase. DNA
Cell Biol. 14: 841-847, 1995.
6. Lyon, M. F.; Scriver, C. R.; Baker, L. R. I.; Tenenhouse, H. S.;
Kronick, J.; Mandla, S.: The Gy mutation: another cause of X-linked
hypophosphatemia in mouse. Proc. Nat. Acad. Sci. 83: 4899-4903,
1986.
7. Meyer, R. A., Jr.; Henley, C. M.; Meyer, M. H.; Morgan, P. L.;
McDonald, A. G.; Mills, C.; Price, D. K.: Partial deletion of both
the spermine synthase gene and the Pex gene in the X-linked hypophosphatemic,
Gyro (Gy) mouse. Genomics 48: 289-295, 1998.
8. Peron, A.; Spaccini, L.; Norris, J.; Bova, S. M.; Selicorni, A.;
Weber, G.; Wood, T.; Schwartz, C. E.; Mastrangelo, M.: Snyder-Robinson
syndrome: a novel nonsense mutation in spermine synthase and expansion
of the phenotype. Am. J. Med. Genet. 161A: 2316-2320, 2013.
9. Snyder, R. D.; Robinson, A.: Recessive sex-linked mental retardation
in the absence of other recognizable abnormalities: report of a family. Clin.
Pediat. 8: 669-674, 1969.
10. Wu, H.; Min, J.; Zeng, H.; McCloskey, D. E.; Ikeguchi, Y.; Loppnau,
P.; Michael, A. J.; Pegg, A. E.; Plotnikov, A. N.: Crystal structure
of human spermine synthase: implications of substrate binding and
catalytic mechanism. J. Biol. Chem. 283: 16135-16146, 2008.
11. Zhang, Z.; Norris, J.; Kalscheuer, V.; Wood, T.; Wang, L.; Schwartz,
C.; Alexov, E.; Van Esch, H.: A Y328C missense mutation in spermine
synthase causes a mild form of Snyder-Robinson syndrome. Hum. Molec.
Genet. 22: 3789-3797, 2013.
*FIELD* CN
Sonja A. Rasmussen - updated: 01/14/2014
Cassandra L. Kniffin - updated: 11/13/2013
Cassandra L. Kniffin - updated: 2/16/2010
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
*FIELD* CD
Victor A. McKusick: 11/6/1997
*FIELD* ED
carol: 01/14/2014
alopez: 11/15/2013
ckniffin: 11/13/2013
carol: 7/20/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 4/2/2009
ckniffin: 2/9/2009
carol: 9/1/2005
ckniffin: 9/1/2005
tkritzer: 5/11/2004
ckniffin: 5/7/2004
carol: 3/22/1999
dholmes: 11/18/1997
mark: 11/7/1997
mark: 11/6/1997
*RECORD*
*FIELD* NO
300105
*FIELD* TI
*300105 SPERMINE SYNTHASE; SMS
*FIELD* TX
DESCRIPTION
Spermine synthase (EC 2.5.1.22) is 1 of 4 enzymes involved in the
read moresynthesis of polyamines from arginine and methionine. The others are
ornithine decarboxylase (165640), S-adenosyl-L-methionine decarboxylase
(180980), and spermidine synthase (182891).
CLONING
Korhonen et al. (1995) isolated and sequenced cDNA clones encoding human
spermine synthase. The open reading frame encodes a 368-amino acid
protein with little sequence similarity to proteins from bacterial and
mammalian sources catalyzing almost identical reactions.
GENE STRUCTURE
Grieff et al. (1997) determined that the SMS gene (which they symbolized
SpS) contains 11 exons spanning 54 kb.
MAPPING
Grieff et al. (1997) mapped the SMS gene 38 kb telomeric to the PHEX
gene (300550) on Xp22.1.
BIOCHEMICAL FEATURES
- Crystal Structure
Wu et al. (2008) determined the crystal structure of human SMS, which is
a dimer of 2 identical subunits. Each monomer has 3 domains: a
C-terminal domain, which contains the active site and is similar in
structure to spermidine synthase; a central domain made up of 4
beta-strands; and an N-terminal domain with structural similarity to
S-adenosylmethionine decarboxylase (AMD1; 180980), the enzyme that forms
the aminopropyl donor substrate. Dimerization occurs mainly through
interactions between the N-terminal domains. Deletion of the N-terminal
domain led to a complete loss of spermine synthase activity, suggesting
that dimerization may be required for activity.
MOLECULAR GENETICS
In affected members of a family with Snyder-Robinson mental retardation
syndrome (MRXSSR; 309583) originally reported by Snyder and Robinson
(1969), Cason et al. (2003) identified a splice site mutation in the SMS
gene (300105.0001).
In 2 Mexican brothers with MRXSSR, Becerra-Solano et al. (2009)
identified a mutation in the SMS gene (V132G; 300105.0003).
In 2 affected males from a Belgian family with a relatively mild form of
Snyder-Robinson mental retardation syndrome, Zhang et al. (2013)
identified a missense mutation in the SMS gene (Y328C; 300105.0004).
In a boy from Italy with Snyder-Robinson syndrome, Peron et al. (2013)
identified a nonsense mutation in the SMS gene (G67X; 300105.0005).
ANIMAL MODEL
First identified as a mouse model for X-linked hypophosphatemia, the
'Gyro' or 'Gy' mouse (see 300550) also exhibits neurologic
abnormalities, including deafness, hyperactivity, circling behavior, and
inner ear abnormalities (Lyon et al., 1986). Meyer et al. (1998) found
that the Gyro mouse has a partial deletion of both the Sms gene and the
Phex gene, making it a contiguous gene syndrome in that species.
However, as mutation in the Phex gene alone results in a
hypophosphatemic phenotype in the mouse (Hyp) without neurologic
manifestations, Meyer et al. (1998) suggested that a deficiency of
spermine may explain the additional neurologic findings in the Gy mouse.
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, IVS4AS, G-A, +5
In affected members of a family with Snyder-Robinson mental retardation
syndrome (309583) originally reported by Snyder and Robinson (1969),
Cason et al. (2003) identified a G-to-A transition at position +5 of the
5-prime splice site of intron 4 of the SMS gene. The mutation segregated
with affected status in the family. Functional studies showed that the
mutation reduced the activity of SMS to 5% of controls. Cason et al.
(2003) noted that the deficiency of spermine in affected patients
suggested a role for polyamines in brain development and cognitive
function. The authors suggested cerebellar dysfunction or defective
functioning of neurons in the red nucleus.
.0002
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, GLY56SER
In affected male members of a Brazilian kindred with Snyder-Robinson
mental retardation syndrome (309583), de Alencastro et al. (2008)
identified a 267G-A transition in exon 2 of the SMS gene, resulting in a
gly56-to-ser (G56S) substitution in the N terminus. The phenotype was
severe, with profound mental retardation and epilepsy. The G56S mutation
segregated with the disease in this family and was not identified in 724
control X chromosomes. Female carriers in the family showed skewed X
inactivation. Patient cell lines showed no detectable SMS enzyme
activity and an increase in spermadine/spermine ratio.
.0003
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, VAL132GLY
In 2 Mexican brothers with Synder-Robinson mental retardation syndrome
(309583), Becerra-Solano et al. (2009) identified a 496T-G transversion
in exon 5 of the SMS gene, resulting in a val132-to-gly (V132G)
substitution in a highly conserved residue between the N-terminal domain
and the linker domain prior to the C-terminal domain that contains the
active site of the enzyme. The mutation was not found in 549 control
chromosomes. Spermine protein and activity were significantly decreased
in both patients but normal in their unaffected mother. The patients had
characteristic features of the disorder, including mental retardation,
osteoporosis, multiple fractures, and facial asymmetry.
.0004
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, TYR328CYS
In 2 affected males from a Belgian family with a relatively mild form of
Snyder-Robinson mental retardation syndrome (309583), Zhang et al.
(2013) identified a c.1084A-G transition in the SMS gene, resulting in a
tyr328-to-cys (Y328C) substitution. The mutation was also present in the
unaffected carrier mother. Biochemical studies showed that the mutant
protein could form a dimer, but there was significantly decreased SMS
activity and a reduction of protein levels to 20% of normal.
Transfection of the mutant protein into PC12 neuronal cells showed that
the Y328C mutation did not result in significantly decreased neurite
length compared to wildtype, and did not cause changes as severe as a
loss-of-function mutation (e.g., 300105.0001). However, molecular
modeling suggested that the Y328C mutations may increase conformational
dynamics of the protein, resulting in destabilization and a loss of
catalytic activity.
.0005
MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE
SMS, GLY67TER
In a boy with Snyder-Robinson syndrome (309583), Peron et al. (2013)
identified a c.200G-A transition in exon 3 of the SMS gene, resulting in
a gly67-to-ter (G67X) substitution. No spermine synthase activity above
baseline was detected in the patient's lymphoblastoid cells. The
patient's mother was heterozygous for the mutation and X-inactivation
analysis showed mild skewing. In addition to features characteristic of
Snyder-Robinson syndrome, the patient also had an ectopic kidney and
early-onset epilepsy.
*FIELD* RF
1. Becerra-Solano, L. E.; Butler, J.; Castaneda-Cisneros, G.; McCloskey,
D. E.; Wang, X.; Pegg, A. E.; Schwartz, C. E.; Sanchez-Corona, J.;
Garcia-Ortiz, J. E.: A missense mutation, p.V132G, in the X-linked
spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am.
J. Med. Genet. 149A: 328-335, 2009.
2. Cason, A. L.; Ikeguchi, Y.; Skinner, C.; Wood, T. C.; Holden, K.
R.; Lubs, H. A.; Martinez, F.; Simensen, R. J.; Stevenson, R. E.;
Pegg, A. E.; Schwartz, C. E.: X-linked spermine synthase gene (SMS)
defect: the first polyamine deficiency syndrome. Europ. J. Hum. Genet. 11:
937-944, 2003.
3. de Alencastro, G.; McCloskey, D. E.; Kliemann, S. E.; Maranduba,
C. M. C.; Pegg, A. E.; Wang, X.; Bertola, D. A.; Schwartz, C. E.;
Passos-Bueno, M. R.; Sertie, A. L.: New SMS mutation leads to a striking
reduction in spermine synthase protein function and a severe form
of Snyder-Robinson X-linked recessive mental retardation syndrome.
(Letter) J. Med. Genet. 45: 539-543, 2008.
4. Grieff, M.; Whyte, M. P.; Thakker, R. V.; Mazzarella, R.: Sequence
analysis of 139 kb in Xp22.1 containing spermine synthase and the
5-prime region of PEX. Genomics 44: 227-231, 1997.
5. Korhonen, V. P.; Halmekyto, M.; Kauppinen, L.; Myohanen, S.; Wahlfors,
J.; Keinanen, T.; Hyvonen, T.; Alhonen, L.; Eloranta, T.; Janne, J.
: Molecular cloning of a cDNA encoding human spermine synthase. DNA
Cell Biol. 14: 841-847, 1995.
6. Lyon, M. F.; Scriver, C. R.; Baker, L. R. I.; Tenenhouse, H. S.;
Kronick, J.; Mandla, S.: The Gy mutation: another cause of X-linked
hypophosphatemia in mouse. Proc. Nat. Acad. Sci. 83: 4899-4903,
1986.
7. Meyer, R. A., Jr.; Henley, C. M.; Meyer, M. H.; Morgan, P. L.;
McDonald, A. G.; Mills, C.; Price, D. K.: Partial deletion of both
the spermine synthase gene and the Pex gene in the X-linked hypophosphatemic,
Gyro (Gy) mouse. Genomics 48: 289-295, 1998.
8. Peron, A.; Spaccini, L.; Norris, J.; Bova, S. M.; Selicorni, A.;
Weber, G.; Wood, T.; Schwartz, C. E.; Mastrangelo, M.: Snyder-Robinson
syndrome: a novel nonsense mutation in spermine synthase and expansion
of the phenotype. Am. J. Med. Genet. 161A: 2316-2320, 2013.
9. Snyder, R. D.; Robinson, A.: Recessive sex-linked mental retardation
in the absence of other recognizable abnormalities: report of a family. Clin.
Pediat. 8: 669-674, 1969.
10. Wu, H.; Min, J.; Zeng, H.; McCloskey, D. E.; Ikeguchi, Y.; Loppnau,
P.; Michael, A. J.; Pegg, A. E.; Plotnikov, A. N.: Crystal structure
of human spermine synthase: implications of substrate binding and
catalytic mechanism. J. Biol. Chem. 283: 16135-16146, 2008.
11. Zhang, Z.; Norris, J.; Kalscheuer, V.; Wood, T.; Wang, L.; Schwartz,
C.; Alexov, E.; Van Esch, H.: A Y328C missense mutation in spermine
synthase causes a mild form of Snyder-Robinson syndrome. Hum. Molec.
Genet. 22: 3789-3797, 2013.
*FIELD* CN
Sonja A. Rasmussen - updated: 01/14/2014
Cassandra L. Kniffin - updated: 11/13/2013
Cassandra L. Kniffin - updated: 2/16/2010
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
*FIELD* CD
Victor A. McKusick: 11/6/1997
*FIELD* ED
carol: 01/14/2014
alopez: 11/15/2013
ckniffin: 11/13/2013
carol: 7/20/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 4/2/2009
ckniffin: 2/9/2009
carol: 9/1/2005
ckniffin: 9/1/2005
tkritzer: 5/11/2004
ckniffin: 5/7/2004
carol: 3/22/1999
dholmes: 11/18/1997
mark: 11/7/1997
mark: 11/6/1997
MIM
309583
*RECORD*
*FIELD* NO
309583
*FIELD* TI
#309583 MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE; MRXSSR
;;SNYDER-ROBINSON MENTAL RETARDATION SYNDROME; SRS
read more*FIELD* TX
A number sign (#) is used with this entry because Snyder-Robinson mental
retardation syndrome (MRXSSR) is caused by mutation in the spermine
synthase gene (SMS; 300105) on chromosome Xp22.
DESCRIPTION
Snyder-Robinson mental retardation syndrome is an X-linked intellectual
disability syndrome with characteristic features including facial
asymmetry, marfanoid habitus, unsteady gait, thickened lower lip, nasal
dysarthic speech, narrow or cleft palate, diminished muscle mass,
osteoporosis, kyphoscoliosis, long great toes, short stature, pectus
carinatum, and myopia (summary by Zhang et al., 2013).
CLINICAL FEATURES
Snyder and Robinson (1969) reported a family in which affected males had
a form of nonspecific X-linked mental retardation with hypotonia and
unsteady gait. Eleven males in 4 generations were affected. Arena et al.
(1992, 1996) reevaluated the family, defining the disorder as a specific
syndrome with the following features: mild to moderate mental
retardation; asthenic body build (marfanoid habitus); diminished muscle
bulk; osteoporosis; kyphoscoliosis; long, thin face; slight facial
asymmetry with a prominent lower lip; nasal voice; high, narrow, or
cleft palate; and long, thin fingers and toes. Carrier females were
clinically normal. Arena et al. (1996) redefined the entity as an
X-linked mental retardation syndrome. In a follow-up of the same family,
Cason et al. (2003) reported that some affected males had an unsteady
gait, nonspecific movement disorder, and seizures. Two of 4 affected
males had an abnormal EEG.
De Alencastro et al. (2008) reported a second family with genetically-
confirmed Snyder-Robinson syndrome (300105.0002). At age 12 years, the
proband had profound mental retardation, seizures, no speech
development, and was unable to stand alone or walk. He had short stature
and mild facial dysmorphism, with mild hypertelorism, exophthalmia,
short philtrum, thickened lower lip, slight high-arched palate,
mandibular prognathism, and ears with prominent antihelices and
hypoplastic lobules. Other features included high myopia, pectus
carinatum, cryptorchidism, severe kyphoscoliosis, camptodactyly without
arachnodactyly, and muscular hypotonia.
Kesler et al. (2009) performed brain MRI studies on 2 affected males
with Snyder-Robinson syndrome reported by Cason et al. (2003), at ages
13 and 39 years, respectively. IQ measurements were 36 and 54,
respectively. Both had dysmorphic facial features; the younger patient
had myoclonic seizures. Total brain volumes of both patients were
somewhat enlarged and affected gray, white, and CSF volumes equally. The
younger patient had disproportionately decreased cerebellar volume, and
both had disproportionately decreased hippocampal and red nucleus
volumes. Kesler et al. (2009) postulated that spermine deficiency may
result in an imbalance between cell growth and pruning mechanisms during
neurodevelopment.
Becerra-Solano et al. (2009) reported 2 adult Mexican brothers with
Snyder-Robinson syndrome. Clinical features included mental retardation,
multiple childhood fractures associated with decreased bone density,
thin body habitus with poor muscle bulk and long thin limbs, pectus
excavatum with widely-spaced nipples, and kyphoscoliosis. Dysmorphic
facial features included brachycephaly, asymmetric facies, slanted upper
palpebral fissures, sparse eyebrows, synophrys, right palpebral ptosis,
high nasal bridge, bulbous nasal tip, anteverted nares, smooth philtrum,
prominent lower lip, high palate, overcrowded teeth, asymmetric ears,
and short webbed neck. Both also had areas of patchy skin
hyperpigmentation. Family history was notable for a spontaneous abortion
in the mother during the first trimester.
Zhang et al. (2013) reported a family in which 4 males in 3 generations
had Snyder-Robinson syndrome. The proband was reported in detail: he had
delayed psychomotor development, delayed language, IQ of 74, thin build,
low-set ears, small mouth, kyphoscoliosis, and long fingers and toes. He
did not have facial asymmetry, or abnormal gait or other neurologic
symptoms. He had good social interaction and attended a special school.
His maternal uncle also went to a special school and worked in a
sheltered environment. Zhang et al. (2013) noted that the phenotype in
these patients was relatively mild compared to that reported in other
patients with this disorder.
Peron et al. (2013) reported a boy from Italy with Snyder-Robinson
syndrome characterized by a thin habitus with decreased muscle mass,
unsteady gait, osteoporosis, kyphoscoliosis, dysmorphic facial features,
cognitive impairment, and nasal speech. In addition to features
typically seen in Snyder-Robinson syndrome, the patient also had an
ectopic right kidney and early onset of epilepsy. Seizure activity was
first observed in the first year of life and he was diagnosed with
atypical West syndrome; at age 6 years, he developed myoclonus and focal
motor seizures. The finding of a mutation in the SMS gene (see MOLECULAR
GENETICS) confirmed the diagnosis of MRXSSR.
MAPPING
By linkage analysis of 17 members of an affected family, Arena et al.
(1996) found a maximum lod score of 4.7 at markers DXS41 and DXS989 on
Xp21.3-p22.12, distal to the 3-prime end of the DMD gene (300377).
MOLECULAR GENETICS
In affected members of the family originally reported by Snyder and
Robinson (1969), Cason et al. (2003) identified a mutation in the SMS
gene (300105.0001).
In 2 Mexican brothers with Snyder-Robinson syndrome, Becerra-Solano et
al. (2009) identified a mutation in the SMS gene (V132G; 300105.0003).
Zhang et al. (2013) reported a patient and his uncle with a mild form of
Snyder-Robinson syndrome who carried a missense mutation in the SMS gene
(Y328C; 300105.0004).
In a boy from Italy with Snyder-Robinson syndrome who had originally
been diagnosed with West syndrome, Peron et al. (2013) identified a
truncating mutation in the SMS gene (300105.0005). In the patient's
lymphoblastoid cells, no spermine synthase activity above baseline was
detected, and the spermine/spermidine ratio was abnormal, consistent
with Snyder-Robinson syndrome. The patient's mother was heterozygous for
the mutation, and X-inactivation analysis showed mild skewing.
*FIELD* RF
1. Arena, J. F.; Schwartz, C.; McClurkin, C.; Miller, M.; Stevenson,
R.; Garza, J.; Nance, M.; Lubs, H. A.: Gene localization and clinical
redefinition of the Snyder-Robinson syndrome. (Abstract) Am. J. Hum.
Genet. 51 (suppl.): A181 only, 1992.
2. Arena, J. F.; Schwartz, C.; Ouzts, L.; Stevenson, R.; Miller, M.;
Garza, J.; Nance, M.; Lubs, H.: X-linked mental retardation with
thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12. Am.
J. Med. Genet. 64: 50-58, 1996.
3. Becerra-Solano, L. E.; Butler, J.; Castaneda-Cisneros, G.; McCloskey,
D. E.; Wang, X.; Pegg, A. E.; Schwartz, C. E.; Sanchez-Corona, J.;
Garcia-Ortiz, J. E.: A missense mutation, p.V132G, in the X-linked
spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am.
J. Med. Genet. 149A: 328-335, 2009.
4. Cason, A. L.; Ikeguchi, Y.; Skinner, C.; Wood, T. C.; Holden, K.
R.; Lubs, H. A.; Martinez, F.; Simensen, R. J.; Stevenson, R. E.;
Pegg, A. E.; Schwartz, C. E.: X-linked spermine synthase gene (SMS)
defect: the first polyamine deficiency syndrome. Europ. J. Hum. Genet. 11:
937-944, 2003.
5. de Alencastro, G.; McCloskey, D. E.; Kliemann, S. E.; Maranduba,
C. M. C.; Pegg, A. E.; Wang, X.; Bertola, D. A.; Schwartz, C. E.;
Passos-Bueno, M. R.; Sertie, A. L.: New SMS mutation leads to a striking
reduction in spermine synthase protein function and a severe form
of Snyder-Robinson X-linked recessive mental retardation syndrome.
(Letter) J. Med. Genet. 45: 539-543, 2008.
6. Kesler, S. R.; Schwartz, C.; Stevenson, R. E.; Reiss, A. L.: The
impact of spermine synthase (SMS) mutations on brain morphology Neurogenetics 10:
299-305, 2009.
7. Peron, A.; Spaccini, L.; Norris, J.; Bova, S. M.; Selicorni, A.;
Weber, G.; Wood, T.; Schwartz, C. E.; Mastrangelo, M.: Snyder-Robinson
syndrome: a novel nonsense mutation in spermine synthase and expansion
of the phenotype. Am. J. Med. Genet. 161A: 2316-2320, 2013.
8. Snyder, R. D.; Robinson, A.: Recessive sex-linked mental retardation
in the absence of other recognizable abnormalities: report of a family. Clin.
Pediat. 8: 669-674, 1969.
9. Zhang, Z.; Norris, J.; Kalscheuer, V.; Wood, T.; Wang, L.; Schwartz,
C.; Alexov, E.; Van Esch, H.: A Y328C missense mutation in spermine
synthase causes a mild form of Snyder-Robinson syndrome. Hum. Molec.
Genet. 22: 3789-3797, 2013.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Tall stature;
Short stature;
[Other];
Thin body build
HEAD AND NECK:
[Face];
Facial asymmetry;
Prognathism;
Short philtrum;
[Ears];
Asymmetric dysplastic ears;
[Eyes];
High myopia;
Hypertelorism, mild;
Slanted palpebral fissures;
[Mouth];
Prominent lower lip;
Small upper lip;
High, narrow palate;
Cleft palate;
Bifid uvula;
[Teeth];
Overcrowded teeth;
[Neck];
Short, webbed neck
CHEST:
[External features];
Widely spaced nipples;
[Ribs, sternum, clavicles, and scapulae];
Pectus excavatum;
Pectus carinatum
GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism
SKELETAL:
Osteoporosis;
Multiple fractures;
[Spine];
Kyphoscoliosis;
[Hands];
Long, thin hands;
Long, hyperextensible fingers;
[Feet];
Long halluces;
Clubfoot
MUSCLE, SOFT TISSUE:
Decreased muscle mass
NEUROLOGIC:
[Central nervous system];
Mental retardation (males);
Hypotonia;
Wide-based gait;
Seizures
VOICE:
Nasal speech;
Dysarthric speech
MISCELLANEOUS:
Variable phenotype;
Carrier females are normal
MOLECULAR BASIS:
Caused by mutation in the spermine synthase gene (SMS, 300105.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 02/16/2010
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
Kelly A. Przylepa - revised: 9/11/2003
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
ckniffin: 02/16/2010
ckniffin: 2/9/2009
ckniffin: 5/7/2004
joanna: 9/15/2003
joanna: 9/12/2003
*FIELD* CN
Sonja A. Rasmussen - updated: 01/14/2014
Cassandra L. Kniffin - updated: 11/13/2013
Cassandra L. Kniffin - updated: 2/16/2010
Cassandra L. Kniffin - updated: 12/10/2009
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
*FIELD* CD
Victor A. McKusick: 11/17/1992
*FIELD* ED
carol: 01/14/2014
alopez: 11/15/2013
ckniffin: 11/13/2013
carol: 7/20/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 12/28/2009
ckniffin: 12/10/2009
wwang: 4/2/2009
ckniffin: 2/9/2009
tkritzer: 5/11/2004
ckniffin: 5/7/2004
mgross: 3/17/2004
carol: 3/13/2002
mimadm: 2/28/1994
carol: 1/20/1993
carol: 11/20/1992
carol: 11/17/1992
*RECORD*
*FIELD* NO
309583
*FIELD* TI
#309583 MENTAL RETARDATION, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE; MRXSSR
;;SNYDER-ROBINSON MENTAL RETARDATION SYNDROME; SRS
read more*FIELD* TX
A number sign (#) is used with this entry because Snyder-Robinson mental
retardation syndrome (MRXSSR) is caused by mutation in the spermine
synthase gene (SMS; 300105) on chromosome Xp22.
DESCRIPTION
Snyder-Robinson mental retardation syndrome is an X-linked intellectual
disability syndrome with characteristic features including facial
asymmetry, marfanoid habitus, unsteady gait, thickened lower lip, nasal
dysarthic speech, narrow or cleft palate, diminished muscle mass,
osteoporosis, kyphoscoliosis, long great toes, short stature, pectus
carinatum, and myopia (summary by Zhang et al., 2013).
CLINICAL FEATURES
Snyder and Robinson (1969) reported a family in which affected males had
a form of nonspecific X-linked mental retardation with hypotonia and
unsteady gait. Eleven males in 4 generations were affected. Arena et al.
(1992, 1996) reevaluated the family, defining the disorder as a specific
syndrome with the following features: mild to moderate mental
retardation; asthenic body build (marfanoid habitus); diminished muscle
bulk; osteoporosis; kyphoscoliosis; long, thin face; slight facial
asymmetry with a prominent lower lip; nasal voice; high, narrow, or
cleft palate; and long, thin fingers and toes. Carrier females were
clinically normal. Arena et al. (1996) redefined the entity as an
X-linked mental retardation syndrome. In a follow-up of the same family,
Cason et al. (2003) reported that some affected males had an unsteady
gait, nonspecific movement disorder, and seizures. Two of 4 affected
males had an abnormal EEG.
De Alencastro et al. (2008) reported a second family with genetically-
confirmed Snyder-Robinson syndrome (300105.0002). At age 12 years, the
proband had profound mental retardation, seizures, no speech
development, and was unable to stand alone or walk. He had short stature
and mild facial dysmorphism, with mild hypertelorism, exophthalmia,
short philtrum, thickened lower lip, slight high-arched palate,
mandibular prognathism, and ears with prominent antihelices and
hypoplastic lobules. Other features included high myopia, pectus
carinatum, cryptorchidism, severe kyphoscoliosis, camptodactyly without
arachnodactyly, and muscular hypotonia.
Kesler et al. (2009) performed brain MRI studies on 2 affected males
with Snyder-Robinson syndrome reported by Cason et al. (2003), at ages
13 and 39 years, respectively. IQ measurements were 36 and 54,
respectively. Both had dysmorphic facial features; the younger patient
had myoclonic seizures. Total brain volumes of both patients were
somewhat enlarged and affected gray, white, and CSF volumes equally. The
younger patient had disproportionately decreased cerebellar volume, and
both had disproportionately decreased hippocampal and red nucleus
volumes. Kesler et al. (2009) postulated that spermine deficiency may
result in an imbalance between cell growth and pruning mechanisms during
neurodevelopment.
Becerra-Solano et al. (2009) reported 2 adult Mexican brothers with
Snyder-Robinson syndrome. Clinical features included mental retardation,
multiple childhood fractures associated with decreased bone density,
thin body habitus with poor muscle bulk and long thin limbs, pectus
excavatum with widely-spaced nipples, and kyphoscoliosis. Dysmorphic
facial features included brachycephaly, asymmetric facies, slanted upper
palpebral fissures, sparse eyebrows, synophrys, right palpebral ptosis,
high nasal bridge, bulbous nasal tip, anteverted nares, smooth philtrum,
prominent lower lip, high palate, overcrowded teeth, asymmetric ears,
and short webbed neck. Both also had areas of patchy skin
hyperpigmentation. Family history was notable for a spontaneous abortion
in the mother during the first trimester.
Zhang et al. (2013) reported a family in which 4 males in 3 generations
had Snyder-Robinson syndrome. The proband was reported in detail: he had
delayed psychomotor development, delayed language, IQ of 74, thin build,
low-set ears, small mouth, kyphoscoliosis, and long fingers and toes. He
did not have facial asymmetry, or abnormal gait or other neurologic
symptoms. He had good social interaction and attended a special school.
His maternal uncle also went to a special school and worked in a
sheltered environment. Zhang et al. (2013) noted that the phenotype in
these patients was relatively mild compared to that reported in other
patients with this disorder.
Peron et al. (2013) reported a boy from Italy with Snyder-Robinson
syndrome characterized by a thin habitus with decreased muscle mass,
unsteady gait, osteoporosis, kyphoscoliosis, dysmorphic facial features,
cognitive impairment, and nasal speech. In addition to features
typically seen in Snyder-Robinson syndrome, the patient also had an
ectopic right kidney and early onset of epilepsy. Seizure activity was
first observed in the first year of life and he was diagnosed with
atypical West syndrome; at age 6 years, he developed myoclonus and focal
motor seizures. The finding of a mutation in the SMS gene (see MOLECULAR
GENETICS) confirmed the diagnosis of MRXSSR.
MAPPING
By linkage analysis of 17 members of an affected family, Arena et al.
(1996) found a maximum lod score of 4.7 at markers DXS41 and DXS989 on
Xp21.3-p22.12, distal to the 3-prime end of the DMD gene (300377).
MOLECULAR GENETICS
In affected members of the family originally reported by Snyder and
Robinson (1969), Cason et al. (2003) identified a mutation in the SMS
gene (300105.0001).
In 2 Mexican brothers with Snyder-Robinson syndrome, Becerra-Solano et
al. (2009) identified a mutation in the SMS gene (V132G; 300105.0003).
Zhang et al. (2013) reported a patient and his uncle with a mild form of
Snyder-Robinson syndrome who carried a missense mutation in the SMS gene
(Y328C; 300105.0004).
In a boy from Italy with Snyder-Robinson syndrome who had originally
been diagnosed with West syndrome, Peron et al. (2013) identified a
truncating mutation in the SMS gene (300105.0005). In the patient's
lymphoblastoid cells, no spermine synthase activity above baseline was
detected, and the spermine/spermidine ratio was abnormal, consistent
with Snyder-Robinson syndrome. The patient's mother was heterozygous for
the mutation, and X-inactivation analysis showed mild skewing.
*FIELD* RF
1. Arena, J. F.; Schwartz, C.; McClurkin, C.; Miller, M.; Stevenson,
R.; Garza, J.; Nance, M.; Lubs, H. A.: Gene localization and clinical
redefinition of the Snyder-Robinson syndrome. (Abstract) Am. J. Hum.
Genet. 51 (suppl.): A181 only, 1992.
2. Arena, J. F.; Schwartz, C.; Ouzts, L.; Stevenson, R.; Miller, M.;
Garza, J.; Nance, M.; Lubs, H.: X-linked mental retardation with
thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12. Am.
J. Med. Genet. 64: 50-58, 1996.
3. Becerra-Solano, L. E.; Butler, J.; Castaneda-Cisneros, G.; McCloskey,
D. E.; Wang, X.; Pegg, A. E.; Schwartz, C. E.; Sanchez-Corona, J.;
Garcia-Ortiz, J. E.: A missense mutation, p.V132G, in the X-linked
spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am.
J. Med. Genet. 149A: 328-335, 2009.
4. Cason, A. L.; Ikeguchi, Y.; Skinner, C.; Wood, T. C.; Holden, K.
R.; Lubs, H. A.; Martinez, F.; Simensen, R. J.; Stevenson, R. E.;
Pegg, A. E.; Schwartz, C. E.: X-linked spermine synthase gene (SMS)
defect: the first polyamine deficiency syndrome. Europ. J. Hum. Genet. 11:
937-944, 2003.
5. de Alencastro, G.; McCloskey, D. E.; Kliemann, S. E.; Maranduba,
C. M. C.; Pegg, A. E.; Wang, X.; Bertola, D. A.; Schwartz, C. E.;
Passos-Bueno, M. R.; Sertie, A. L.: New SMS mutation leads to a striking
reduction in spermine synthase protein function and a severe form
of Snyder-Robinson X-linked recessive mental retardation syndrome.
(Letter) J. Med. Genet. 45: 539-543, 2008.
6. Kesler, S. R.; Schwartz, C.; Stevenson, R. E.; Reiss, A. L.: The
impact of spermine synthase (SMS) mutations on brain morphology Neurogenetics 10:
299-305, 2009.
7. Peron, A.; Spaccini, L.; Norris, J.; Bova, S. M.; Selicorni, A.;
Weber, G.; Wood, T.; Schwartz, C. E.; Mastrangelo, M.: Snyder-Robinson
syndrome: a novel nonsense mutation in spermine synthase and expansion
of the phenotype. Am. J. Med. Genet. 161A: 2316-2320, 2013.
8. Snyder, R. D.; Robinson, A.: Recessive sex-linked mental retardation
in the absence of other recognizable abnormalities: report of a family. Clin.
Pediat. 8: 669-674, 1969.
9. Zhang, Z.; Norris, J.; Kalscheuer, V.; Wood, T.; Wang, L.; Schwartz,
C.; Alexov, E.; Van Esch, H.: A Y328C missense mutation in spermine
synthase causes a mild form of Snyder-Robinson syndrome. Hum. Molec.
Genet. 22: 3789-3797, 2013.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Tall stature;
Short stature;
[Other];
Thin body build
HEAD AND NECK:
[Face];
Facial asymmetry;
Prognathism;
Short philtrum;
[Ears];
Asymmetric dysplastic ears;
[Eyes];
High myopia;
Hypertelorism, mild;
Slanted palpebral fissures;
[Mouth];
Prominent lower lip;
Small upper lip;
High, narrow palate;
Cleft palate;
Bifid uvula;
[Teeth];
Overcrowded teeth;
[Neck];
Short, webbed neck
CHEST:
[External features];
Widely spaced nipples;
[Ribs, sternum, clavicles, and scapulae];
Pectus excavatum;
Pectus carinatum
GENITOURINARY:
[Internal genitalia, male];
Cryptorchidism
SKELETAL:
Osteoporosis;
Multiple fractures;
[Spine];
Kyphoscoliosis;
[Hands];
Long, thin hands;
Long, hyperextensible fingers;
[Feet];
Long halluces;
Clubfoot
MUSCLE, SOFT TISSUE:
Decreased muscle mass
NEUROLOGIC:
[Central nervous system];
Mental retardation (males);
Hypotonia;
Wide-based gait;
Seizures
VOICE:
Nasal speech;
Dysarthric speech
MISCELLANEOUS:
Variable phenotype;
Carrier females are normal
MOLECULAR BASIS:
Caused by mutation in the spermine synthase gene (SMS, 300105.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 02/16/2010
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
Kelly A. Przylepa - revised: 9/11/2003
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
ckniffin: 02/16/2010
ckniffin: 2/9/2009
ckniffin: 5/7/2004
joanna: 9/15/2003
joanna: 9/12/2003
*FIELD* CN
Sonja A. Rasmussen - updated: 01/14/2014
Cassandra L. Kniffin - updated: 11/13/2013
Cassandra L. Kniffin - updated: 2/16/2010
Cassandra L. Kniffin - updated: 12/10/2009
Cassandra L. Kniffin - updated: 2/9/2009
Cassandra L. Kniffin - updated: 5/7/2004
*FIELD* CD
Victor A. McKusick: 11/17/1992
*FIELD* ED
carol: 01/14/2014
alopez: 11/15/2013
ckniffin: 11/13/2013
carol: 7/20/2011
wwang: 2/18/2010
ckniffin: 2/16/2010
wwang: 12/28/2009
ckniffin: 12/10/2009
wwang: 4/2/2009
ckniffin: 2/9/2009
tkritzer: 5/11/2004
ckniffin: 5/7/2004
mgross: 3/17/2004
carol: 3/13/2002
mimadm: 2/28/1994
carol: 1/20/1993
carol: 11/20/1992
carol: 11/17/1992