SGPP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that SGPP1 is active in the ER membrane. This is correct and directly supported by experimental confocal co-localization of the human protein with the ER marker calreticulin, and by the multipass membrane topology. Supporting Evidence: PMID:12815058 green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin
GO:0046839 phospholipid dephosphorylation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: General "phospholipid dephosphorylation" transferred by phylogeny. S1P is a phosphorylated sphingoid lipid, so this parent term is not wrong, but it is far less informative than the specific sphingosine-1-phosphate phosphatase activity and sphingosine metabolic process terms that capture the actual function. Kept as non-core because it under-specifies the substrate class.
GO:0042392 sphingosine-1-phosphate phosphatase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the core molecular function. Redundant with the experimental IDA/EXP annotations to the same term but correct; represents the defining activity of the protein. Supporting Evidence: PMID:12815058 Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P
GO:0006670 sphingosine metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: SGPP1 generates free sphingosine from S1P, and this sphingosine is recycled into the sphingolipid biosynthesis pathway. This is a core biological process for the enzyme; well supported by the demonstrated fall in cellular sphingosine on knockdown and by the UniProt-documented recycling role. Supporting Evidence: PMID:12815058 Sphingolipid mass measurements in hSPPase1 siRNA knockdown cells revealed a 2-fold increase of S1P levels and concomitant decrease in sphingosine
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt SubCell electronic mapping to ER membrane. Correct and consistent with the experimental localization; redundant with the EXP annotation. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269\|PubMed:12815058}
GO:0005886 plasma membrane	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Electronic SubCell mapping to plasma membrane. In UniProt the "Cell membrane" location is asserted only By similarity to the mouse ortholog (Q9JI99), with no human experimental support; the demonstrated site of the human enzyme is the ER membrane. Treated as an over-annotation for the human protein rather than removed, since it derives from a curated ortholog inference. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Cell membrane {ECO:0000250\|UniProtKB:Q9JI99}
GO:0030149 sphingolipid catabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning annotation to sphingolipid catabolic process. S1P dephosphorylation is a degradative/turnover step on S1P, but the net physiological role is recycling sphingosine back into sphingolipid synthesis rather than net sphingolipid breakdown. Retained as non-core (also captured by the Reactome TAS to the same term).
GO:0042392 sphingosine-1-phosphate phosphatase activity	IEA GO_REF:0000120	ACCEPT	Summary: Multi-method electronic annotation (ARBA + RHEA) of the core S1P phosphatase activity. Correct; redundant with experimental annotations. Supporting Evidence: PMID:12815058 Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P
GO:0070780 dihydrosphingosine-1-phosphate phosphatase activity	IEA GO_REF:0000116	ACCEPT	Summary: RHEA-based electronic annotation for the dihydro-S1P (sphinganine 1-phosphate) phosphatase reaction (RHEA:27514), a UniProt-documented catalytic activity of SGPP1. Correct; also supported experimentally. Supporting Evidence: PMID:12815058 Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P
GO:0045616 regulation of keratinocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara electronic transfer from the mouse ortholog (Q9JI99) of a role in keratinocyte differentiation. UniProt records this epidermal role only By similarity. Plausible but not demonstrated for the human protein and not part of the core enzymatic function; kept as a non-core, ortholog-derived process. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Involved in the regulation of epidermal homeostasis and keratinocyte differentiation (By similarity)
GO:0045682 regulation of epidermis development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl Compara electronic transfer from mouse Q9JI99 of a role in epidermis development, mirroring the By-similarity epidermal-homeostasis statement in UniProt. Same rationale as the keratinocyte-differentiation term; retained as non-core. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Involved in the regulation of epidermal homeostasis and keratinocyte differentiation (By similarity)
GO:0030149 sphingolipid catabolic process	TAS Reactome:R-HSA-9845614	KEEP AS NON CORE	Summary: Reactome pathway assertion placing SGPP1 in sphingolipid catabolism. As with the ARBA annotation, S1P dephosphorylation is a turnover step but the dominant physiological outcome is recycling into synthesis; retained as non-core.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: HPA immunofluorescence (IDA) annotation to nucleoplasm. This is inconsistent with a nine-transmembrane ER-membrane enzyme and is most likely a high-throughput IF artifact or antibody cross-reactivity; no other evidence supports a nuclear pool. Marked as over-annotation rather than removed because it is an experimental (IDA) annotation whose full underlying image data were not reviewed here.
GO:0005789 endoplasmic reticulum membrane	EXP PMID:12815058 Role of human sphingosine-1-phosphate phosphatase 1 in the r...	ACCEPT	Summary: Direct experimental localization of the human enzyme to the ER membrane by confocal co-localization with calreticulin. This is the authoritative, core subcellular location. Supporting Evidence: PMID:12815058 green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin
GO:0005886 plasma membrane	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Sequence-similarity (ISS) transfer of a plasma-membrane/cell-membrane location from the mouse ortholog Q9JI99. There is no human experimental evidence for a plasma-membrane pool; the demonstrated location is the ER membrane. Over-annotation of the human protein. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Cell membrane {ECO:0000250\|UniProtKB:Q9JI99}
GO:0042392 sphingosine-1-phosphate phosphatase activity	EXP PMID:12815058 Role of human sphingosine-1-phosphate phosphatase 1 in the r...	ACCEPT	Summary: Experimental demonstration (overexpression increases, and siRNA knockdown decreases, S1P-directed phosphatase activity; knockdown raises cellular/secreted S1P) of the defining molecular function. Core function. Supporting Evidence: PMID:12815058 Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P
GO:0070780 dihydrosphingosine-1-phosphate phosphatase activity	EXP PMID:12815058 Role of human sphingosine-1-phosphate phosphatase 1 in the r...	ACCEPT	Summary: Experimental demonstration that the enzyme also dephosphorylates dihydro-S1P (sphinganine 1-phosphate). A genuine, distinct catalytic activity of SGPP1. Supporting Evidence: PMID:12815058 Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P
GO:0042392 sphingosine-1-phosphate phosphatase activity	TAS Reactome:R-HSA-428664	ACCEPT	Summary: Reactome traceable-author-statement for the S1P phosphatase reaction (SGPP1,2 dephosphorylate sphingoid-1-phosphates). Correct and consistent with the experimental annotations to the same core activity.
GO:0035621 ER to Golgi ceramide transport	IMP PMID:16782891 Sphingosine-1-phosphate phosphohydrolase regulates endoplasm...	KEEP AS NON CORE	Summary: Experimental (IMP) annotation based on the finding that SPP-1 overexpression, in the presence of S1P, raises ER ceramide and inhibits ER-to-Golgi trafficking of a fluorescent ceramide analog (and of a protein cargo). SGPP1 thus regulates ER-to-Golgi ceramide transport, a downstream consequence of its control of ER ceramide levels rather than the enzyme's primary function; retained as a well-supported non-core process. Supporting Evidence: PMID:16782891 SPP-1 regulates ceramide levels in the ER and thus influences the anterograde membrane transport of both ceramide and proteins from the ER to the Golgi apparatus
GO:0042392 sphingosine-1-phosphate phosphatase activity	IDA PMID:16782891 Sphingosine-1-phosphate phosphohydrolase regulates endoplasm...	ACCEPT	Summary: Direct-assay (IDA) confirmation of S1P phosphatase activity in the study of ceramide trafficking, consistent with the substrate specificity documented in UniProt. Core molecular function. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Specifically dephosphorylates sphingosine 1-phosphate (S1P), dihydro-S1P, and phyto-S1P. Does not act on ceramide 1-phosphate, lysophosphatidic acid or phosphatidic acid (PubMed:16782891)
GO:0045616 regulation of keratinocyte differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS) transfer from mouse Q9JI99 of a keratinocyte differentiation role, matching the By-similarity epidermal statement in UniProt. Retained as non-core, ortholog-derived; not part of the core enzymatic function. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Involved in the regulation of epidermal homeostasis and keratinocyte differentiation (By similarity)
GO:0045682 regulation of epidermis development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity (ISS) transfer from mouse Q9JI99 of an epidermis development role. Same rationale as the keratinocyte-differentiation ISS annotation; retained as non-core. Supporting Evidence: file:human/SGPP1/SGPP1-uniprot.txt Involved in the regulation of epidermal homeostasis and keratinocyte differentiation (By similarity)
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-428664	ACCEPT	Summary: Reactome traceable-author-statement placing the SGPP1 dephosphorylation reaction at the ER membrane. Consistent with the experimental localization; correct. Supporting Evidence: PMID:12815058 green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin

Gene Description

Existing Annotations Review

Core Functions

Sphingosine-1-phosphate phosphatase that dephosphorylates sphingosine 1-phosphate (and dihydro-S1P) to sphingosine plus phosphate at the endoplasmic reticulum membrane, recycling sphingosine into sphingolipid metabolism and setting intracellular S1P levels (the sphingolipid rheostat).

Dihydrosphingosine-1-phosphate (sphinganine 1-phosphate) phosphatase activity, dephosphorylating dihydro-S1P to sphinganine at the ER membrane as part of sphingoid-base recycling.

References

📚 Additional Documentation

Notes

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