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Protein

Spermine synthase

Gene

SMS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).

Catalytic activityi

S-adenosyl 3-(methylthio)propylamine + spermidine = S-methyl-5'-thioadenosine + spermine.

Pathwayi: spermine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes spermine from spermidine.
Proteins known to be involved in this subpathway in this organism are:
  1. Spermine synthase (SMS)
This subpathway is part of the pathway spermine biosynthesis, which is itself part of Amine and polyamine biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes spermine from spermidine, the pathway spermine biosynthesis and in Amine and polyamine biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei148 – 1481S-adenosylmethioninamine
Binding sitei177 – 1771Spermidine
Binding sitei201 – 2011Spermidine
Binding sitei220 – 2201S-adenosylmethioninamine
Active sitei276 – 2761Proton acceptorPROSITE-ProRule annotation
Binding sitei351 – 3511Spermidine
Binding sitei353 – 3531Spermidine

GO - Molecular functioni

GO - Biological processi

  • methionine metabolic process Source: ProtInc
  • polyamine metabolic process Source: Reactome
  • spermine biosynthetic process Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Polyamine biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS02362-MONOMER.
BRENDAi2.5.1.22. 2681.
ReactomeiR-HSA-351202. Metabolism of polyamines.
SABIO-RKP52788.
UniPathwayiUPA00249; UER00315.

Names & Taxonomyi

Protein namesi
Recommended name:
Spermine synthase (EC:2.5.1.22)
Short name:
SPMSY
Alternative name(s):
Spermidine aminopropyltransferase
Gene namesi
Name:SMS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:11123. SMS.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive.
See also OMIM:309583
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561G → S in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076449
Natural varianti58 – 581F → L in MRXSSR. 1 Publication
Corresponds to variant rs397515549 [ dbSNP | Ensembl ].
VAR_072748
Natural varianti67 – 671G → E in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076450
Natural varianti132 – 1321V → G in MRXSSR. 1 Publication
VAR_076451
Natural varianti328 – 3281Y → C in MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076452

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi201 – 2011D → A or N: 100,000-fold decrease in catalytic efficiency. 1 Publication
Mutagenesisi276 – 2761D → N: 200,000-fold decrease in catalytic efficiency. 1 Publication
Mutagenesisi353 – 3531E → Q: 800-fold decrease in catalytic efficiency. 1 Publication

Keywords - Diseasei

Mental retardation

Organism-specific databases

MalaCardsiSMS.
MIMi309583. phenotype.
Orphaneti3063. X-linked intellectual disability, Snyder type.
PharmGKBiPA35972.

Chemistry

ChEMBLiCHEMBL4934.
DrugBankiDB00127. Spermine.

Polymorphism and mutation databases

BioMutaiSMS.
DMDMi8247960.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 366365Spermine synthasePRO_0000156538Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei57 – 571PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP52788.
MaxQBiP52788.
PaxDbiP52788.
PeptideAtlasiP52788.
PRIDEiP52788.

2D gel databases

OGPiP52788.

PTM databases

iPTMnetiP52788.
PhosphoSiteiP52788.

Expressioni

Gene expression databases

BgeeiENSG00000102172.
CleanExiHS_SMS.
ExpressionAtlasiP52788. baseline and differential.
GenevisibleiP52788. HS.

Organism-specific databases

HPAiHPA029849.
HPA029852.

Interactioni

Subunit structurei

Homodimer. Dimerization is mediated through the N-terminal domain and seems to be required for activity as deletion of the N-terminal domain causes complete loss of activity.1 Publication

Protein-protein interaction databases

BioGridi112495. 44 interactions.
IntActiP52788. 17 interactions.
MINTiMINT-5002620.
STRINGi9606.ENSP00000385746.

Chemistry

BindingDBiP52788.

Structurei

Secondary structure

1
366
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi5 – 128Combined sources
Helixi21 – 3212Combined sources
Beta strandi36 – 427Combined sources
Turni43 – 453Combined sources
Beta strandi46 – 527Combined sources
Beta strandi58 – 636Combined sources
Beta strandi67 – 759Combined sources
Helixi85 – 9814Combined sources
Beta strandi114 – 1174Combined sources
Beta strandi136 – 1449Combined sources
Beta strandi149 – 1557Combined sources
Turni156 – 1583Combined sources
Beta strandi159 – 1646Combined sources
Beta strandi167 – 1715Combined sources
Helixi175 – 1817Combined sources
Turni182 – 1854Combined sources
Beta strandi193 – 1986Combined sources
Helixi203 – 2097Combined sources
Beta strandi214 – 2218Combined sources
Helixi223 – 23210Combined sources
Helixi234 – 2374Combined sources
Beta strandi242 – 2465Combined sources
Beta strandi249 – 2546Combined sources
Helixi256 – 26611Combined sources
Beta strandi270 – 2767Combined sources
Helixi291 – 30414Combined sources
Beta strandi306 – 31813Combined sources
Helixi322 – 33211Combined sources
Beta strandi335 – 3373Combined sources
Beta strandi339 – 3468Combined sources
Helixi349 – 3513Combined sources
Beta strandi355 – 3628Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C6KX-ray1.95A/B/C/D5-366[»]
3C6MX-ray2.45A/B/C/D5-366[»]
ProteinModelPortaliP52788.
SMRiP52788. Positions 3-365.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52788.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini122 – 362241PABSPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni255 – 2562S-adenosylmethioninamine binding

Domaini

Composed of 3 domains: the N-terminal domain has structural similarity to S-adenosylmethionine decarboxylase, the central domain is made up of four beta strands and the C-terminal domain is similar in structure to spermidine synthase. The N- and C-terminal domains are both required for activity.

Sequence similaritiesi

Contains 1 PABS (polyamine biosynthesis) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1562. Eukaryota.
COG0421. LUCA.
GeneTreeiENSGT00620000088036.
HOGENOMiHOG000007053.
HOVERGENiHBG004512.
InParanoidiP52788.
KOiK00802.
OMAiEGRMFDY.
OrthoDBiEOG091G0BXC.
PhylomeDBiP52788.
TreeFamiTF324508.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR030374. PABS.
IPR030373. PABS_CS.
IPR029063. SAM-dependent_MTases.
IPR015576. Spermine_synthase_animal.
[Graphical view]
PANTHERiPTHR11558:SF27. PTHR11558:SF27. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS01330. PABS_1. 1 hit.
PS51006. PABS_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P52788-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAARHSTLD FMLGAKADGE TILKGLQSIF QEQGMAESVH TWQDHGYLAT
60 70 80 90 100
YTNKNGSFAN LRIYPHGLVL LDLQSYDGDA QGKEEIDSIL NKVEERMKEL
110 120 130 140 150
SQDSTGRVKR LPPIVRGGAI DRYWPTADGR LVEYDIDEVV YDEDSPYQNI
160 170 180 190 200
KILHSKQFGN ILILSGDVNL AESDLAYTRA IMGSGKEDYT GKDVLILGGG
210 220 230 240 250
DGGILCEIVK LKPKMVTMVE IDQMVIDGCK KYMRKTCGDV LDNLKGDCYQ
260 270 280 290 300
VLIEDCIPVL KRYAKEGREF DYVINDLTAV PISTSPEEDS TWEFLRLILD
310 320 330 340 350
LSMKVLKQDG KYFTQGNCVN LTEALSLYEE QLGRLYCPVE FSKEIVCVPS
360
YLELWVFYTV WKKAKP
Length:366
Mass (Da):41,268
Last modified:May 30, 2000 - v2
Checksum:iD5B23EF61DE66443
GO
Isoform 2 (identifier: P52788-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     57-109: Missing.

Note: Gene prediction confirmed by EST data.
Show »
Length:313
Mass (Da):35,278
Checksum:i7D237FC4CD55D3E6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 11M → MPG in CAA88921 (PubMed:7546290).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561G → S in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076449
Natural varianti58 – 581F → L in MRXSSR. 1 Publication
Corresponds to variant rs397515549 [ dbSNP | Ensembl ].
VAR_072748
Natural varianti60 – 601N → S.1 Publication
VAR_071048
Natural varianti67 – 671G → E in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076450
Natural varianti132 – 1321V → G in MRXSSR. 1 Publication
VAR_076451
Natural varianti328 – 3281Y → C in MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 Publication
VAR_076452

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei57 – 10953Missing in isoform 2. CuratedVSP_034406Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49099 mRNA. Translation: CAA88921.1.
AD001528 mRNA. Translation: AAB61308.1.
AK313834 mRNA. Translation: BAG36567.1.
U53331 Genomic DNA. Translation: AAD08634.1.
U73023 Genomic DNA. No translation available.
CH471074 Genomic DNA. Translation: EAW98984.1.
BC009898 mRNA. Translation: AAH09898.1.
BC085621 mRNA. Translation: AAH85621.1.
CCDSiCCDS14203.1. [P52788-1]
CCDS59161.1. [P52788-2]
PIRiS54160.
RefSeqiNP_001245352.1. NM_001258423.1. [P52788-2]
NP_004586.2. NM_004595.4. [P52788-1]
UniGeneiHs.724874.

Genome annotation databases

EnsembliENST00000379404; ENSP00000368714; ENSG00000102172. [P52788-2]
ENST00000404933; ENSP00000385746; ENSG00000102172. [P52788-1]
GeneIDi6611.
KEGGihsa:6611.
UCSCiuc004dag.5. human. [P52788-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49099 mRNA. Translation: CAA88921.1.
AD001528 mRNA. Translation: AAB61308.1.
AK313834 mRNA. Translation: BAG36567.1.
U53331 Genomic DNA. Translation: AAD08634.1.
U73023 Genomic DNA. No translation available.
CH471074 Genomic DNA. Translation: EAW98984.1.
BC009898 mRNA. Translation: AAH09898.1.
BC085621 mRNA. Translation: AAH85621.1.
CCDSiCCDS14203.1. [P52788-1]
CCDS59161.1. [P52788-2]
PIRiS54160.
RefSeqiNP_001245352.1. NM_001258423.1. [P52788-2]
NP_004586.2. NM_004595.4. [P52788-1]
UniGeneiHs.724874.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3C6KX-ray1.95A/B/C/D5-366[»]
3C6MX-ray2.45A/B/C/D5-366[»]
ProteinModelPortaliP52788.
SMRiP52788. Positions 3-365.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112495. 44 interactions.
IntActiP52788. 17 interactions.
MINTiMINT-5002620.
STRINGi9606.ENSP00000385746.

Chemistry

BindingDBiP52788.
ChEMBLiCHEMBL4934.
DrugBankiDB00127. Spermine.

PTM databases

iPTMnetiP52788.
PhosphoSiteiP52788.

Polymorphism and mutation databases

BioMutaiSMS.
DMDMi8247960.

2D gel databases

OGPiP52788.

Proteomic databases

EPDiP52788.
MaxQBiP52788.
PaxDbiP52788.
PeptideAtlasiP52788.
PRIDEiP52788.

Protocols and materials databases

DNASUi6611.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379404; ENSP00000368714; ENSG00000102172. [P52788-2]
ENST00000404933; ENSP00000385746; ENSG00000102172. [P52788-1]
GeneIDi6611.
KEGGihsa:6611.
UCSCiuc004dag.5. human. [P52788-1]

Organism-specific databases

CTDi6611.
GeneCardsiSMS.
GeneReviewsiSMS.
HGNCiHGNC:11123. SMS.
HPAiHPA029849.
HPA029852.
MalaCardsiSMS.
MIMi300105. gene.
309583. phenotype.
neXtProtiNX_P52788.
Orphaneti3063. X-linked intellectual disability, Snyder type.
PharmGKBiPA35972.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1562. Eukaryota.
COG0421. LUCA.
GeneTreeiENSGT00620000088036.
HOGENOMiHOG000007053.
HOVERGENiHBG004512.
InParanoidiP52788.
KOiK00802.
OMAiEGRMFDY.
OrthoDBiEOG091G0BXC.
PhylomeDBiP52788.
TreeFamiTF324508.

Enzyme and pathway databases

UniPathwayiUPA00249; UER00315.
BioCyciMetaCyc:HS02362-MONOMER.
BRENDAi2.5.1.22. 2681.
ReactomeiR-HSA-351202. Metabolism of polyamines.
SABIO-RKP52788.

Miscellaneous databases

EvolutionaryTraceiP52788.
GeneWikiiSMS_(gene).
GenomeRNAii6611.
PROiP52788.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102172.
CleanExiHS_SMS.
ExpressionAtlasiP52788. baseline and differential.
GenevisibleiP52788. HS.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR030374. PABS.
IPR030373. PABS_CS.
IPR029063. SAM-dependent_MTases.
IPR015576. Spermine_synthase_animal.
[Graphical view]
PANTHERiPTHR11558:SF27. PTHR11558:SF27. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS01330. PABS_1. 1 hit.
PS51006. PABS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPSY_HUMAN
AccessioniPrimary (citable) accession number: P52788
Secondary accession number(s): A6NHA7
, A6NI34, B2R9M0, O00544, Q9UQS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: September 7, 2016
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.