Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform.
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Cloning and characterization of human/mouse SPHK2; SPHK2 expression raises SPP levels, with dihydrosphingosine a better substrate than sphingosine and a tissue distribution distinct from SPHK1.
"Expression of SPHK2 in HEK 293 cells resulted in elevated SPP levels. d-erythro-dihydrosphingosine was a better substrate than d-erythro-sphingosine for SPHK2."
Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling.
Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.
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VEGF-induced Ras-GTP/phospho-ERK accumulation is blocked by siRNA against SPK1 but not SPK2, indicating the effect is SPHK1-dependent.
"Small interfering RNA (siRNA) that targets SPK1, but not SPK2, blocks VEGF-induced accumulation of Ras-GTP and phospho-ERK in T24 cells."
Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis.
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SPHK2 localizes to the nucleus (functional NLS) as well as the cytosol and inhibits DNA synthesis, arresting cells at G1/S.
"When SPHK2 was transiently expressed in various cell lines, it was localized in the nuclei as well as in the cytosol, whereas SPHK1 was distributed in the cytosol but not in the nucleus."
Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis.
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The human-specific N-terminal-extended SPHK2-L (isoform 1) translocates to the nucleus on serum deprivation; SPHK2 knockdown blocks serum-deprivation/drug-induced apoptosis.
"serum deprivation resulted in the translocation of SPHK2-L into the nuclei."
SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism.
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SPHK2 (putative BH3-only protein) inhibits cell growth, enhances apoptosis, and raises C16-ceramide, opposite to pro-survival SPHK1; ER-targeting converts SPHK1 to pro-apoptotic.
"In contrast to pro-survival SphK1, the putative BH3-only protein SphK2 inhibits cell growth and enhances apoptosis."
Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2.
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PKD phosphorylates a serine in a SPHK2 nuclear export signal, driving PMA-induced nuclear export; this regulates SPHK2 subcellular localization.
"phosphorylation of SPHK2 catalyzed by protein kinase D (PKD), which regulates its localization."
Integral and associated lysosomal membrane proteins.
Eukaryotic elongation factor 1A interacts with sphingosine kinase and directly enhances its catalytic activity.
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eEF1A1 directly interacts with SPHK2 and increases its catalytic activity ~2.6-fold in vitro (also for SPHK1), a novel mechanism of sphingosine kinase regulation.
"As with SK1, GST-eEF1A1 was shown to
increase SK2 activity by ∼2.6-fold"
Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate.
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Nuclear SPHK2 associates with histone H3 and produces S1P that binds and inhibits HDAC1/ HDAC2, increasing histone acetylation and transcription of p21 and c-fos.
"S1P specifically bound to the histone deacetylases HDAC1 and HDAC2 and inhibited their enzymatic activity, preventing the removal of acetyl groups from lysine residues within histone tails."
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SPHK2 binds specifically to histone H3 (not H4/H2B/H2A), placing it in nucleosomes/ chromatin.
"Only H3, but not histones H4, H2B, or H2A, bound to SphK2"
Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
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During apoptosis, SPHK2 is cleaved at its N-terminus by caspase-1 and a truncated but enzymatically active fragment is released from cells.
"During cell death, sphingosine kinase 2 (SphK2) is cleaved at its N-terminus in a caspase-1-dependent manner. Thereupon, a truncated but enzymatically active fragment of SphK2 is released from cells."
Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration.
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Mitochondrial S1P made mainly by SPHK2 binds prohibitin 2 (PHB2); loss of SPHK2 or PHB2 disrupts cytochrome-c oxidase (complex IV) assembly and mitochondrial respiration.
"S1P, produced in the mitochondria mainly by sphingosine kinase 2 (SphK2), binds with high affinity and specificity to prohibitin 2 (PHB2)"
Sphingosine 1-phosphate induces filopodia formation through S1PR2 activation of ERM proteins.
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S1P-driven ERM phosphorylation/filopodia formation acts through the receptor S1PR2, with endogenous S1P generated predominantly by SPHK1; SPHK2 was one of the knockdown controls.
"endogenously generated predominantly by the action of SK1"
Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer's disease brain.
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In Alzheimer's disease brains, neuronal SPHK2 shifts from cytosol to nucleus and cleaved SPHK2 increases; cytosolic SPHK2 decreases with amyloid density.
"SphK2 is preferentially localized in the nucleus in AD brain extracts as compared to control extracts, with a marked increase of cleaved SphK2."
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Sphingolipid de novo biosynthesis
SPHK2 binds SPHK2 inhibitors
SPHK2 phosphorylates sphingoid