Sphingosine kinase 1 (SK 1) (SPK 1) (EC 2.7.1.91) (Acetyltransferase SPHK1) (EC 2.3.1.-)
1_MDPAG 6_ GPRGV 11_ LPRPC 16_ RVLVL 21_ LNPRG 26_ GKGKA 31_ LQLFR 36_ SHVQP 41_ LLAEA 46_ EISFT 51_ LMLTE 56_ RRNHA 61_ RELVR 66_ SEELG 71_ RWDAL 76_ VVMSG 81_ DGLMH 86_ EVVNG 91_ LMERP 96_ DWETA 101_ IQKPL 106_ CSLPA 111_ GSGNA 116_ LAASL 121_ NHYAG 126_ YEQVT 131_ NEDLL 136_ TNCTL 141_ LLCRR 146_ LLSPM 151_ NLLSL 156_ HTASG 161_ LRLFS 166_ VLSLA 171_ WGFIA 176_ DVDLE 181_ SEKYR 186_ RLGEM 191_ RFTLG 196_ TFLRL 201_ AALRT 206_ YRGRL 211_ AYLPV 216_ GRVGS 221_ KTPAS 226_ PVVVQ 231_ QGPVD 236_ AHLVP 241_ LEEPV 246_ PSHWT 251_ VVPDE 256_ DFVLV 261_ LALLH 266_ SHLGS 271_ EMFAA 276_ PMGRC 281_ AAGVM 286_ HLFYV 291_ RAGVS 296_ RAMLL 301_ RLFLA 306_ MEKGR 311_ HMEYE 316_ CPYLV 321_ YVPVV 326_ AFRLE 331_ PKDGK 336_ GVFAV 341_ DGELM 346_ VSEAV 351_ QGQVH 356_ PNYFW 361_ MVSGC 366_ VEPPP 371_ SWKPQ 376_QMPPP
1: Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also 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 (PubMed:11923095, PubMed:20577214, PubMed:23602659, PubMed:24929359, PubMed:29662056). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). 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 (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). 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 (PubMed:24929359, PubMed:28049734). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698)
2: Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia