ID SPEE_HUMAN Reviewed; 302 AA.
AC P19623; B1AKP9; Q15511;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 27-MAR-2024, entry version 220.
DE RecName: Full=Spermidine synthase;
DE Short=SPDSY;
DE EC=2.5.1.16;
DE AltName: Full=Putrescine aminopropyltransferase;
GN Name=SRM; Synonyms=SPS1, SRML1;
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].
RX PubMed=2344393; DOI=10.1089/dna.1990.9.103;
RA Wahlfors J., Alhonen L., Kauppinen L., Hyvoenen T., Jaenne J., Eloranta T.;
RT "Human spermidine synthase: cloning and primary structure.";
RL DNA Cell Biol. 9:103-110(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2069720; DOI=10.1089/dna.1991.10.467;
RA Myoehaenen S., Kauppinen L., Wahlfors J., Alhonen L., Jaenne J.;
RT "Human spermidine synthase gene: structure and chromosomal localization.";
RL DNA Cell Biol. 10:467-474(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, 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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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 [7]
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) IN COMPLEXES WITH SPERMIDINE;
RP PUTRESCINE; MTA AND S-ADENOSYLMETHIONINAMINE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=17585781; DOI=10.1021/bi602498k;
RA Wu H., Min J., Ikeguchi Y., Zeng H., Dong A., Loppnau P., Pegg A.E.,
RA Plotnikov A.N.;
RT "Structure and mechanism of spermidine synthases.";
RL Biochemistry 46:8331-8339(2007).
CC -!- FUNCTION: Catalyzes the production of spermidine from putrescine and
CC decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference
CC for putrescine as substrate, and has very low activity towards 1,3-
CC diaminopropane. Has extremely low activity towards spermidine.
CC {ECO:0000269|PubMed:17585781}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=putrescine + S-adenosyl 3-(methylsulfanyl)propylamine = H(+) +
CC S-methyl-5'-thioadenosine + spermidine; Xref=Rhea:RHEA:12721,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:57443,
CC ChEBI:CHEBI:57834, ChEBI:CHEBI:326268; EC=2.5.1.16;
CC Evidence={ECO:0000269|PubMed:17585781};
CC -!- ACTIVITY REGULATION: The activity is thought to be regulated mainly by
CC the availability of decarboxylated S-adenosylmethionine.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for putrescine {ECO:0000269|PubMed:17585781};
CC KM=0.9 uM for S-adenosylmethioninamine {ECO:0000269|PubMed:17585781};
CC -!- PATHWAY: Amine and polyamine biosynthesis; spermidine biosynthesis;
CC spermidine from putrescine: step 1/1.
CC -!- SUBUNIT: Homodimer or homotetramer. {ECO:0000269|PubMed:17585781}.
CC -!- INTERACTION:
CC P19623; P19623: SRM; NbExp=6; IntAct=EBI-1056183, EBI-1056183;
CC P19623; P54274: TERF1; NbExp=2; IntAct=EBI-1056183, EBI-710997;
CC -!- SIMILARITY: Belongs to the spermidine/spermine synthase family.
CC {ECO:0000305}.
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DR EMBL; M34338; AAA36633.1; -; mRNA.
DR EMBL; M64231; AAA60574.1; -; Genomic_DNA.
DR EMBL; AL109811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71675.1; -; Genomic_DNA.
DR EMBL; BC000309; AAH00309.1; -; mRNA.
DR EMBL; BC033106; AAH33106.1; -; mRNA.
DR CCDS; CCDS125.1; -.
DR PIR; A32610; A32610.
DR RefSeq; NP_003123.2; NM_003132.2.
DR PDB; 2O05; X-ray; 2.00 A; A/B=1-302.
DR PDB; 2O06; X-ray; 2.00 A; A/B=1-302.
DR PDB; 2O07; X-ray; 1.89 A; A/B=1-302.
DR PDB; 2O0L; X-ray; 1.99 A; A/B=1-302.
DR PDB; 3RW9; X-ray; 2.00 A; A/B=1-302.
DR PDBsum; 2O05; -.
DR PDBsum; 2O06; -.
DR PDBsum; 2O07; -.
DR PDBsum; 2O0L; -.
DR PDBsum; 3RW9; -.
DR AlphaFoldDB; P19623; -.
DR SMR; P19623; -.
DR BioGRID; 112601; 64.
DR IntAct; P19623; 13.
DR STRING; 9606.ENSP00000366156; -.
DR BindingDB; P19623; -.
DR ChEMBL; CHEMBL4232; -.
DR DrugBank; DB00118; Ademetionine.
DR GlyGen; P19623; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P19623; -.
DR MetOSite; P19623; -.
DR PhosphoSitePlus; P19623; -.
DR SwissPalm; P19623; -.
DR BioMuta; SRM; -.
DR DMDM; 134811; -.
DR EPD; P19623; -.
DR jPOST; P19623; -.
DR MassIVE; P19623; -.
DR MaxQB; P19623; -.
DR PaxDb; 9606-ENSP00000366156; -.
DR PeptideAtlas; P19623; -.
DR ProteomicsDB; 53682; -.
DR Pumba; P19623; -.
DR Antibodypedia; 13673; 285 antibodies from 28 providers.
DR DNASU; 6723; -.
DR Ensembl; ENST00000376957.7; ENSP00000366156.2; ENSG00000116649.10.
DR GeneID; 6723; -.
DR KEGG; hsa:6723; -.
DR MANE-Select; ENST00000376957.7; ENSP00000366156.2; NM_003132.3; NP_003123.2.
DR UCSC; uc001arz.2; human.
DR AGR; HGNC:11296; -.
DR CTD; 6723; -.
DR DisGeNET; 6723; -.
DR GeneCards; SRM; -.
DR HGNC; HGNC:11296; SRM.
DR HPA; ENSG00000116649; Low tissue specificity.
DR MIM; 182891; gene.
DR neXtProt; NX_P19623; -.
DR OpenTargets; ENSG00000116649; -.
DR PharmGKB; PA36120; -.
DR VEuPathDB; HostDB:ENSG00000116649; -.
DR eggNOG; KOG1562; Eukaryota.
DR GeneTree; ENSGT00870000136521; -.
DR HOGENOM; CLU_048199_3_1_1; -.
DR InParanoid; P19623; -.
DR OMA; FLYHEMM; -.
DR OrthoDB; 1126121at2759; -.
DR PhylomeDB; P19623; -.
DR TreeFam; TF314466; -.
DR BioCyc; MetaCyc:HS04027-MONOMER; -.
DR BRENDA; 2.5.1.16; 2681.
DR PathwayCommons; P19623; -.
DR Reactome; R-HSA-351202; Metabolism of polyamines.
DR SABIO-RK; P19623; -.
DR SignaLink; P19623; -.
DR UniPathway; UPA00248; UER00314.
DR BioGRID-ORCS; 6723; 54 hits in 1164 CRISPR screens.
DR ChiTaRS; SRM; human.
DR EvolutionaryTrace; P19623; -.
DR GenomeRNAi; 6723; -.
DR Pharos; P19623; Tchem.
DR PRO; PR:P19623; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P19623; Protein.
DR Bgee; ENSG00000116649; Expressed in body of pancreas and 200 other cell types or tissues.
DR ExpressionAtlas; P19623; baseline and differential.
DR Genevisible; P19623; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004766; F:spermidine synthase activity; IDA:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0006595; P:polyamine metabolic process; TAS:Reactome.
DR GO; GO:0008295; P:spermidine biosynthetic process; IDA:UniProtKB.
DR CDD; cd02440; AdoMet_MTases; 1.
DR Gene3D; 2.30.140.10; Spermidine synthase, tetramerisation domain; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR HAMAP; MF_00198; Spermidine_synth; 1.
DR InterPro; IPR030374; PABS.
DR InterPro; IPR030373; PABS_CS.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001045; Spermi_synthase.
DR InterPro; IPR030668; Spermi_synthase_euk.
DR InterPro; IPR035246; Spermidine_synt_N.
DR InterPro; IPR037163; Spermidine_synt_N_sf.
DR NCBIfam; TIGR00417; speE; 1.
DR PANTHER; PTHR11558:SF11; SPERMIDINE SYNTHASE; 1.
DR PANTHER; PTHR11558; SPERMIDINE/SPERMINE SYNTHASE; 1.
DR Pfam; PF17284; Spermine_synt_N; 1.
DR Pfam; PF01564; Spermine_synth; 1.
DR PIRSF; PIRSF000502; Spermidine_synth; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR PROSITE; PS01330; PABS_1; 1.
DR PROSITE; PS51006; PABS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Polyamine biosynthesis; Reference proteome;
KW Spermidine biosynthesis; Transferase.
FT CHAIN 1..302
FT /note="Spermidine synthase"
FT /id="PRO_0000156445"
FT DOMAIN 18..253
FT /note="PABS"
FT ACT_SITE 173
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 49
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 79
FT /ligand="putrescine"
FT /ligand_id="ChEBI:CHEBI:326268"
FT BINDING 80
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 104
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 124
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 155..156
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 173..176
FT /ligand="putrescine"
FT /ligand_id="ChEBI:CHEBI:326268"
FT BINDING 173
FT /ligand="S-adenosyl 3-(methylsulfanyl)propylamine"
FT /ligand_id="ChEBI:CHEBI:57443"
FT BINDING 241
FT /ligand="putrescine"
FT /ligand_id="ChEBI:CHEBI:326268"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT VARIANT 149
FT /note="L -> V (in dbSNP:rs1049932)"
FT /id="VAR_011807"
FT CONFLICT 210
FT /note="Q -> E (in Ref. 1; AAA36633)"
FT /evidence="ECO:0000305"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 31..45
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 47..59
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:2O07"
FT TURN 73..76
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 106..111
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 179..185
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 188..196
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 197..208
FT /evidence="ECO:0007829|PDB:2O07"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 214..227
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 229..237
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 245..254
FT /evidence="ECO:0007829|PDB:2O07"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 268..273
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 281..286
FT /evidence="ECO:0007829|PDB:2O07"
FT HELIX 292..299
FT /evidence="ECO:0007829|PDB:2O07"
SQ SEQUENCE 302 AA; 33825 MW; 3EF454D886F6425D CRC64;
MEPGPDGPAA SGPAAIREGW FRETCSLWPG QALSLQVEQL LHHRRSRYQD ILVFRSKTYG
NVLVLDGVIQ CTERDEFSYQ EMIANLPLCS HPNPRKVLII GGGDGGVLRE VVKHPSVESV
VQCEIDEDVI QVSKKFLPGM AIGYSSSKLT LHVGDGFEFM KQNQDAFDVI ITDSSDPMGP
AESLFKESYY QLMKTALKED GVLCCQGECQ WLHLDLIKEM RQFCQSLFPV VAYAYCTIPT
YPSGQIGFML CSKNPSTNFQ EPVQPLTQQQ VAQMQLKYYN SDVHRAAFVL PEFARKALND
VS
//
