TARGETID

T86014

FORMERID

TTDI02179

UNIPROID

SPHK1_HUMAN

TARGNAME

Sphingosine kinase 1 (SPHK1)

GENENAME

SPHK1

TARGTYPE

Clinical trial target

SYNONYMS

SPK 1; SPK; SPHK1; SK 1; Acetyltransferase SPHK1

FUNCTION

Acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis. Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion. In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES inducion through p38 MAPK signaling pathway. Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity. In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA. Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions.

PDBSTRUC

4V24; 4L02; 3VZD; 3VZC; 3VZB

BIOCLASS

Kinase

ECNUMBER

EC 2.7.1.91

SEQUENCE

MDPAGGPRGVLPRPCRVLVLLNPRGGKGKALQLFRSHVQPLLAEAEISFTLMLTERRNHARELVRSEELGRWDALVVMSGDGLMHEVVNGLMERPDWETAIQKPLCSLPAGSGNALAASLNHYAGYEQVTNEDLLTNCTLLLCRRLLSPMNLLSLHTASGLRLFSVLSLAWGFIADVDLESEKYRRLGEMRFTLGTFLRLAALRTYRGRLAYLPVGRVGSKTPASPVVVQQGPVDAHLVPLEEPVPSHWTVVPDEDFVLVLALLHSHLGSEMFAAPMGRCAAGVMHLFYVRAGVSRAMLLRLFLAMEKGRHMEYECPYLVYVPVVAFRLEPKDGKGVFAVDGELMVSEAVQGQVHPNYFWMVSGCVEPPPSWKPQQMPPPEEPL

DRUGINFO

Phenoxodiol

DRUGINFO

GSK618334

DRUGINFO

Methylbenzenesulfonamide derivative 1

DRUGINFO

PMID27539678-Compound-10

DRUGINFO

PMID27539678-Compound-11

DRUGINFO

PMID27539678-Compound-12

DRUGINFO

PMID27539678-Compound-13

DRUGINFO

PMID27539678-Compound-14