SMS

Gene Description

SMS encodes spermine synthase (spermidine aminopropyltransferase; EC 2.5.1.22), a cytosolic enzyme that catalyzes the final committed step of polyamine biosynthesis. It transfers an aminopropyl group from decarboxylated S-adenosylmethionine (dcSAM, produced by AMD1) onto spermidine, yielding the higher polyamine spermine plus 5'-methylthioadenosine (MTA). Spermine synthase is an obligate homodimer; each subunit comprises three domains — a C-terminal catalytic domain resembling spermidine synthase, a central four-stranded beta lid, and an N-terminal domain with structural similarity to S-adenosylmethionine decarboxylase that mediates dimerization required for activity. The enzyme belongs to the spermidine/spermine synthase (aminopropyltransferase) family and is ubiquitously expressed. Loss-of-function variants in the X-linked SMS gene cause Snyder-Robinson syndrome, an X-linked recessive syndromic intellectual disability with osteoporosis, hypotonia/hypertonia, marfanoid habitus and unsteady gait, reflecting an altered spermine/spermidine balance from impaired spermine biosynthesis.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006597 spermine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to spermine biosynthetic process. This is the correct core biological process for SMS: it catalyzes the sole spermine-forming step (spermidine + dcSAM -> spermine + MTA). Well supported by UniProt PATHWAY and by the experimental structure/activity data. Supporting Evidence: file:human/SMS/SMS-uniprot.txt Amine and polyamine biosynthesis; spermine biosynthesis;
GO:0016768 spermine synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) annotation to the correct molecular function, spermine synthase activity (EC 2.5.1.22). This is the defining catalytic activity of the gene product and is corroborated by direct experimental evidence (crystal structure and kinetics, PMID:18367445). Core function. Supporting Evidence: file:human/SMS/SMS-uniprot.txt spermine + S-methyl-5'-thioadenosine + H(+)
GO:0005829 cytosol	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (ARBA) annotation to cytosol. SMS is a soluble cytosolic biosynthetic enzyme with no signal peptide or transmembrane segments; the cytosolic location is independently supported by Reactome (TAS). Correct core location.
GO:0006595 polyamine metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation to polyamine metabolic process. This is correct but a broad grouping-level parent; the specific process (spermine biosynthetic process, GO:0006597) is separately annotated and better captures the gene's role. Retained as non-core.
GO:0006597 spermine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (InterPro IPR015576 / UniPathway UPA00249) to spermine biosynthetic process. Consistent with the phylogenetic and experimental evidence for the core biological process; a valid duplicate of the IBA annotation.
GO:0016768 spermine synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA / InterPro IPR015576 / RHEA:19973 / EC:2.5.1.22) to spermine synthase activity. Correct core molecular function; supported by the mapped Rhea reaction and EC number and by direct experimental evidence.
GO:0006595 polyamine metabolic process	TAS Reactome:R-HSA-351202	KEEP AS NON CORE	Summary: Reactome (TAS) annotation to polyamine metabolic process via the "Metabolism of polyamines" pathway. Correct but a broad parent term; the specific spermine biosynthetic process is separately annotated. Retained as non-core.
GO:0016768 spermine synthase activity	EXP PMID:18367445 Crystal structure of human spermine synthase: implications o...	ACCEPT	Summary: Experimental (EXP) annotation to spermine synthase activity from the crystal-structure study, which solved ternary complexes with substrate/product, confirmed catalytic activity (EC 2.5.1.22) and identified catalytic residues (Asp201, Asp276, Glu353) by site-directed mutagenesis (>100,000-fold losses in kcat/Km). This is the strongest evidence for the core molecular function. Supporting Evidence: PMID:18367445 The crystal structures of two ternary complexes of human spermine synthase (EC 2.5.1.22)
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: High-throughput (HDA) localization to extracellular exosome from a shotgun proteomic survey of ~900 proteins in urinary/expressed-prostatic-secretion exosome preparations. SMS was detected as one of many co-purifying proteins and was not individually characterized; it is a soluble cytosolic biosynthetic enzyme with no known function at this site. This is an over-annotation for a metabolic enzyme, likely reflecting bulk co-isolation. Retained (not removed) but flagged as over-annotated. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected.
GO:0005829 cytosol	TAS Reactome:R-HSA-351210	ACCEPT	Summary: Reactome (TAS) annotation to cytosol, from the curated spermine-synthesis reaction. Consistent with a soluble cytosolic enzyme and with the ARBA cytosol annotation. Correct core location.
GO:0006595 polyamine metabolic process	TAS PMID:9299240 Sequence analysis of 139 kb in Xp22.1 containing spermine sy...	KEEP AS NON CORE	Summary: TAS annotation to polyamine metabolic process citing the genomic-sequencing paper, which describes SMS as "a ubiquitous enzyme of polyamine metabolism". Correct but a broad grouping term; the specific spermine biosynthetic process is separately annotated. Retained as non-core. Supporting Evidence: PMID:9299240 spermine synthase (SpS), which encodes a ubiquitous enzyme of polyamine metabolism

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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