Free for academic non-profit institutions. Other users need a Commercial license
The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]
SPHK1 (Sphingosine Kinase 1) is a Protein Coding gene. Diseases associated with SPHK1 include Renal Fibrosis and Salivary Gland Carcinoma. Among its related pathways are Signaling by GPCR and S1P3 pathway. Gene Ontology (GO) annotations related to this gene include magnesium ion binding and protein phosphatase 2A binding. An important paralog of this gene is SPHK2.
Sphingosine kinase (SphK) mediates the conversion of sphingosine to sphingosine-1-phosphate, a key sphingolipid signaling molecule involved in cell growth, survival, differentiation and motility. Two mammalian isoforms have been cloned - SPHK1 and SPHK2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IDA | 10947957 |
GO:0001727 | lipid kinase activity | IBA | 21873635 |
GO:0003677 | DNA binding | IDA | 12393916 |
GO:0003951 | NAD+ kinase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | ISS | -- |
GO:0005737 | cytoplasm | IBA,IDA | 15623571 |
GO:0005768 | endosome | IEA | -- |
GO:0005829 | cytosol | TAS | 10863092 |
GO:0005886 | plasma membrane | IEA,IDA | 19854831 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Sphingolipid metabolism | ||
2 | Metabolism |
.40
|
|
3 | Development VEGF signaling via VEGFR2 - generic cascades |
Development VEGF signaling and activation
.42
Development VEGF signaling via VEGFR2 - generic cascades
.42
|
|
4 | Chaperonin-mediated protein folding |
.94
|
|
5 | RET signaling |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001568 | blood vessel development | IEA | -- |
GO:0003376 | sphingosine-1-phosphate receptor signaling pathway | IEA | -- |
GO:0006457 | protein folding | TAS | -- |
GO:0006473 | protein acetylation | ISS | -- |
GO:0006665 | sphingolipid metabolic process | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Fingolimod | Approved, Investigational | Pharma | Enzyme, substrate, inhibitor | 0 | ||
Magnesium | Approved, Experimental, Investigational | Pharma | 0 | |||
Sphingosine | Experimental | Pharma | 0 | |||
Ceramide NG | Experimental | Pharma | 0 | |||
ATP | Investigational | Nutra | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
sphinganine 1-phosphate |
|
19794-97-9 | ||||
ADP |
|
58-64-0 |
|
|||
Cer(d18:0/12:0) |
|
|
||||
Cer(d18:0/14:0) |
|
67030-48-2 |
|
|||
Cer(d18:0/16:0) |
|
5966-29-0 |
|
Compound | Action | Cas Number |
---|---|---|
MP A08 | Selective ATP competitive SphK1 and 2 inhibitor; cell permeable | 219832-49-2 |
N,N-Dimethylsphingosine | Sphingosine kinase inhibitor | 119567-63-4 |
PF 543 hydrochloride | Potent and selective SphK1 inhibitor | 1706522-79-3 |
SKI II | Selective non-lipid inhibitor of sphingosine kinase | 312636-16-1 |
Compound | Action | Cas Number |
---|---|---|
PF-543 | SphK1 inhibitor,cell-permeate,potent and selective | 1415562-82-1 |
PF-543 Citrate | SphK1 inhibitor,potent and cell-permeate | 1415562-83-2 |
SKI II | Sphingosine kinase(SK) inhibitor | 312636-16-1 |
ExUns: | 1 | ^ | 2 | ^ | 3a | · | 3b | ^ | 4 | ^ | 5a | · | 5b | · | 5c | · | 5d | ^ | 6a | · | 6b | · | 6c | ^ | 7a | · | 7b | · | 7c | · | 7d | ^ | 8 | ^ | 9a | · | 9b | · | 9c | · | 9d | ^ | 10a | · | 10b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||
SP6: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||
SP8: | - | - | - | ||||||||||||||||||||||||||||||||||||||||||
SP9: | - | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||
SP10: | - | - | |||||||||||||||||||||||||||||||||||||||||||
SP11: |
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | SPHK1 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Dog (Canis familiaris) |
Mammalia | SPHK1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | SPHK1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Sphk1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Sphk1 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | SPHK1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | SPHK1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | SPHK1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | sphk1 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | LOC100331840 30 |
|
||
SPHK1 31 |
|
OneToOne | |||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP006995 30 |
|
||
Fruit Fly (Drosophila melanogaster) |
Insecta | Sk2 30 31 |
|
ManyToMany | |
Sk1 31 32 |
|
ManyToMany | |||
Worm (Caenorhabditis elegans) |
Secernentea | C34C6.5 32 |
|
|
|
sphk-1 31 |
|
OneToMany | |||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | LCB4 31 |
|
ManyToMany | |
LCB5 31 33 |
|
ManyToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 17 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs138977514 | Benign: not provided | 76,387,028(+) |
T/C NM_001142601.2(SPHK1):c.597T>C (p.Arg199=) |
SYNONYMOUS | |
rs200800534 | Benign: not provided | 76,385,986(+) |
G/C NM_001142601.2(SPHK1):c.12G>C (p.Ala4=) |
SYNONYMOUS | |
rs201987985 | Likely Benign: not provided | 76,385,481(+) |
C/A NM_001142601.2(SPHK1):c.-164C>A |
MISSENSE_VARIANT,FIVE_PRIME_UTR | |
rs549579958 | Likely Benign: not provided | 76,387,026(+) |
CG/C NM_001142601.2(SPHK1):c.596del (p.Arg199fs) |
FRAMESHIFT | |
rs56341546 | Benign: not provided | 76,387,567(+) |
C/T NM_001142601.2(SPHK1):c.1136C>T (p.Pro379Leu) |
MISSENSE |
Disorder | Aliases | PubMed IDs |
---|---|---|
renal fibrosis |
|
|
salivary gland carcinoma |
|
|
glioblastoma |
|
|
estrogen-receptor positive breast cancer |
|
|
brachydactyly, type e1 |
|
|