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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)DescriptionActionsGraphical viewLength
Binding sitei148S-adenosylmethioninamine1
Binding sitei177Spermidine1
Binding sitei201Spermidine1
Binding sitei220S-adenosylmethioninamine1
Active sitei276Proton acceptorPROSITE-ProRule annotation1
Binding sitei351Spermidine1
Binding sitei353Spermidine1

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.
ZFISH: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)DescriptionActionsGraphical viewLength
Natural variantiVAR_07644956G → S in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs121434610dbSNPEnsembl.1
Natural variantiVAR_07274858F → L in MRXSSR. 1 PublicationCorresponds to variant rs397515549dbSNPEnsembl.1
Natural variantiVAR_07645067G → E in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs397515550dbSNPEnsembl.1
Natural variantiVAR_076451132V → G in MRXSSR. 1 PublicationCorresponds to variant rs267607076dbSNPEnsembl.1
Natural variantiVAR_076452328Y → C in MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs397515553dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi201D → A or N: 100,000-fold decrease in catalytic efficiency. 1 Publication1
Mutagenesisi276D → N: 200,000-fold decrease in catalytic efficiency. 1 Publication1
Mutagenesisi353E → Q: 800-fold decrease in catalytic efficiency. 1 Publication1

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi6611.
MalaCardsiSMS.
MIMi309583. phenotype.
OpenTargetsiENSG00000102172.
Orphaneti3063. X-linked intellectual disability, Snyder type.
PharmGKBiPA35972.

Chemistry databases

ChEMBLiCHEMBL4934.
DrugBankiDB00127. Spermine.

Polymorphism and mutation databases

BioMutaiSMS.
DMDMi8247960.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001565382 – 366Spermine synthaseAdd BLAST365

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei57PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP52788.
MaxQBiP52788.
PaxDbiP52788.
PeptideAtlasiP52788.
PRIDEiP52788.

2D gel databases

OGPiP52788.

PTM databases

iPTMnetiP52788.
PhosphoSitePlusiP52788.

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 interactors.
IntActiP52788. 17 interactors.
MINTiMINT-5002620.
STRINGi9606.ENSP00000385746.

Chemistry databases

BindingDBiP52788.

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Helixi21 – 32Combined sources12
Beta strandi36 – 42Combined sources7
Turni43 – 45Combined sources3
Beta strandi46 – 52Combined sources7
Beta strandi58 – 63Combined sources6
Beta strandi67 – 75Combined sources9
Helixi85 – 98Combined sources14
Beta strandi114 – 117Combined sources4
Beta strandi136 – 144Combined sources9
Beta strandi149 – 155Combined sources7
Turni156 – 158Combined sources3
Beta strandi159 – 164Combined sources6
Beta strandi167 – 171Combined sources5
Helixi175 – 181Combined sources7
Turni182 – 185Combined sources4
Beta strandi193 – 198Combined sources6
Helixi203 – 209Combined sources7
Beta strandi214 – 221Combined sources8
Helixi223 – 232Combined sources10
Helixi234 – 237Combined sources4
Beta strandi242 – 246Combined sources5
Beta strandi249 – 254Combined sources6
Helixi256 – 266Combined sources11
Beta strandi270 – 276Combined sources7
Helixi291 – 304Combined sources14
Beta strandi306 – 318Combined sources13
Helixi322 – 332Combined sources11
Beta strandi335 – 337Combined sources3
Beta strandi339 – 346Combined sources8
Helixi349 – 351Combined sources3
Beta strandi355 – 362Combined sources8

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP52788.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini122 – 362PABSPROSITE-ProRule annotationAdd BLAST241

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni255 – 256S-adenosylmethioninamine binding2

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.
GeneTreeiENSGT00860000133776.
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)DescriptionActionsGraphical viewLength
Sequence conflicti1M → MPG in CAA88921 (PubMed:7546290).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07644956G → S in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs121434610dbSNPEnsembl.1
Natural variantiVAR_07274858F → L in MRXSSR. 1 PublicationCorresponds to variant rs397515549dbSNPEnsembl.1
Natural variantiVAR_07104860N → S.1 Publication1
Natural variantiVAR_07645067G → E in MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs397515550dbSNPEnsembl.1
Natural variantiVAR_076451132V → G in MRXSSR. 1 PublicationCorresponds to variant rs267607076dbSNPEnsembl.1
Natural variantiVAR_076452328Y → C in MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis. 1 PublicationCorresponds to variant rs397515553dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03440657 – 109Missing in isoform 2. CuratedAdd BLAST53

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3C6KX-ray1.95A/B/C/D5-366[»]
3C6MX-ray2.45A/B/C/D5-366[»]
ProteinModelPortaliP52788.
SMRiP52788.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP52788.
ChEMBLiCHEMBL4934.
DrugBankiDB00127. Spermine.

PTM databases

iPTMnetiP52788.
PhosphoSitePlusiP52788.

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.
DisGeNETi6611.
GeneCardsiSMS.
GeneReviewsiSMS.
HGNCiHGNC:11123. SMS.
HPAiHPA029849.
HPA029852.
MalaCardsiSMS.
MIMi300105. gene.
309583. phenotype.
neXtProtiNX_P52788.
OpenTargetsiENSG00000102172.
Orphaneti3063. X-linked intellectual disability, Snyder type.
PharmGKBiPA35972.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1562. Eukaryota.
COG0421. LUCA.
GeneTreeiENSGT00860000133776.
HOGENOMiHOG000007053.
HOVERGENiHBG004512.
InParanoidiP52788.
KOiK00802.
OMAiEGRMFDY.
OrthoDBiEOG091G0BXC.
PhylomeDBiP52788.
TreeFamiTF324508.

Enzyme and pathway databases

UniPathwayiUPA00249; UER00315.
BioCyciMetaCyc:HS02362-MONOMER.
ZFISH: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: November 30, 2016
This is version 157 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.