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Protein

Sphingosine kinase 1

Gene

Sphk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

ATP + sphinganine = ADP + sphinganine 1-phosphate.
ATP + sphingosine = ADP + sphingosine 1-phosphate.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei81 – 811Proton donor/acceptorBy similarity
Binding sitei86 – 861ATPPROSITE-ProRule annotation
Binding sitei178 – 1781SubstrateBy similarity
Binding sitei185 – 1851ATPPROSITE-ProRule annotation
Binding sitei191 – 1911ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi22 – 243ATPPROSITE-ProRule annotation
Nucleotide bindingi54 – 585ATPPROSITE-ProRule annotation
Nucleotide bindingi111 – 1133ATPPROSITE-ProRule annotation
Nucleotide bindingi340 – 3423ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.91. 3474.
ReactomeiREACT_275351. Association of TriC/CCT with target proteins during biosynthesis.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_335233. Sphingolipid de novo biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingosine kinase 1 (EC:2.7.1.91)
Short name:
SK 1
Short name:
SPK 1
Gene namesi
Name:Sphk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1316649. Sphk1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Cell membrane By similarity

  • Note: Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 382382Sphingosine kinase 1PRO_0000333032Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei193 – 1931PhosphothreonineBy similarity
Modified residuei225 – 2251PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8CI15.
PRIDEiQ8CI15.

PTM databases

PhosphoSiteiQ8CI15.

Expressioni

Gene expression databases

BgeeiQ8CI15.
ExpressionAtlasiQ8CI15. baseline and differential.
GenevisibleiQ8CI15. MM.

Interactioni

Subunit structurei

Binds to calmodulin. Interacts with SPHKAP. Interacts with CIB1, the interaction occurs in a calcium-dependent manner (By similarity). Interacts with ACY1.By similarity1 Publication

Protein-protein interaction databases

IntActiQ8CI15. 3 interactions.
STRINGi10090.ENSMUSP00000131010.

Structurei

3D structure databases

ProteinModelPortaliQ8CI15.
SMRiQ8CI15. Positions 7-361.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 159148DAGKcPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni79 – 824Substrate bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi147 – 1559Nuclear export signal 1By similarity
Motifi161 – 1699Nuclear export signal 2By similarity

Sequence similaritiesi

Contains 1 DAGKc domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG1597.
GeneTreeiENSGT00690000101761.
HOGENOMiHOG000111460.
HOVERGENiHBG054796.
InParanoidiQ8CI15.
KOiK04718.
OMAiLEREDWS.
OrthoDBiEOG7PCJGK.
PhylomeDBiQ8CI15.
TreeFamiTF354296.

Family and domain databases

InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
IPR016064. NAD/diacylglycerol_kinase.
[Graphical view]
PfamiPF00781. DAGK_cat. 1 hit.
[Graphical view]
SMARTiSM00046. DAGKc. 1 hit.
[Graphical view]
SUPFAMiSSF111331. SSF111331. 2 hits.
PROSITEiPS50146. DAGK. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CI15-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPVECPRGL LPRPCRVLVL LNPQGGKGKA LQLFQSRVQP FLEEAEITFK
60 70 80 90 100
LILTERKNHA RELVCAEELG HWDALAVMSG DGLMHEVVNG LMERPDWETA
110 120 130 140 150
IQKPLCSLPG GSGNALAASV NHYAGYEQVT NEDLLINCTL LLCRRRLSPM
160 170 180 190 200
NLLSLHTASG LRLYSVLSLS WGFVADVDLE SEKYRRLGEI RFTVGTFFRL
210 220 230 240 250
ASLRIYQGQL AYLPVGTVAS KRPASTLVQK GPVDTHLVPL EEPVPSHWTV
260 270 280 290 300
VPEQDFVLVL VLLHTHLSSE LFAAPMGRCE AGVMHLFYVR AGVSRAALLR
310 320 330 340 350
LFLAMQKGKH MELDCPYLVH VPVVAFRLEP RSQRGVFSVD GELMVCEAVQ
360 370 380
GQVHPNYLWM VCGSRDAPSG RDSRRGPPPE EP
Length:382
Mass (Da):42,443
Last modified:March 1, 2003 - v1
Checksum:iB791FAA58FCE3D29
GO
Isoform 2 (identifier: Q8CI15-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MEP → MWWCCVLFV

Show »
Length:388
Mass (Da):43,254
Checksum:i01EB032322542CAD
GO
Isoform 3 (identifier: Q8CI15-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     4-4: Missing.

Show »
Length:381
Mass (Da):42,344
Checksum:i2F2C1F10D59EB129
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti146 – 1461R → H in BAE33198 (PubMed:9726979).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 33MEP → MWWCCVLFV in isoform 2. 1 PublicationVSP_033448
Alternative sequencei4 – 41Missing in isoform 3. 1 PublicationVSP_033449

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068749 mRNA. Translation: AAC61698.1.
AF415213 mRNA. Translation: AAL07499.1.
AK155332 mRNA. Translation: BAE33198.1.
AK160900 mRNA. Translation: BAE36079.1.
AL645851 Genomic DNA. Translation: CAM17116.1.
AL645851 Genomic DNA. Translation: CAM17117.1.
BC037710 mRNA. Translation: AAH37710.1.
CCDSiCCDS25668.1. [Q8CI15-1]
CCDS25669.1. [Q8CI15-2]
CCDS48986.1. [Q8CI15-3]
RefSeqiNP_001165943.1. NM_001172472.1. [Q8CI15-1]
NP_001165944.1. NM_001172473.1. [Q8CI15-1]
NP_001165946.1. NM_001172475.1. [Q8CI15-3]
NP_035581.1. NM_011451.3. [Q8CI15-2]
NP_079643.2. NM_025367.6. [Q8CI15-1]
XP_006532733.1. XM_006532670.2. [Q8CI15-3]
XP_006532734.1. XM_006532671.2. [Q8CI15-3]
XP_006532735.1. XM_006532672.2. [Q8CI15-3]
XP_006532736.1. XM_006532673.2. [Q8CI15-1]
UniGeneiMm.20944.

Genome annotation databases

EnsembliENSMUST00000063396; ENSMUSP00000064743; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000063446; ENSMUSP00000067865; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000100201; ENSMUSP00000097775; ENSMUSG00000061878. [Q8CI15-3]
ENSMUST00000106386; ENSMUSP00000101994; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000106387; ENSMUSP00000101995; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000106388; ENSMUSP00000101996; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000141798; ENSMUSP00000131010; ENSMUSG00000061878. [Q8CI15-2]
GeneIDi20698.
KEGGimmu:20698.
UCSCiuc007mlg.2. mouse. [Q8CI15-3]
uc007mlh.2. mouse. [Q8CI15-1]
uc007mll.2. mouse. [Q8CI15-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF068749 mRNA. Translation: AAC61698.1.
AF415213 mRNA. Translation: AAL07499.1.
AK155332 mRNA. Translation: BAE33198.1.
AK160900 mRNA. Translation: BAE36079.1.
AL645851 Genomic DNA. Translation: CAM17116.1.
AL645851 Genomic DNA. Translation: CAM17117.1.
BC037710 mRNA. Translation: AAH37710.1.
CCDSiCCDS25668.1. [Q8CI15-1]
CCDS25669.1. [Q8CI15-2]
CCDS48986.1. [Q8CI15-3]
RefSeqiNP_001165943.1. NM_001172472.1. [Q8CI15-1]
NP_001165944.1. NM_001172473.1. [Q8CI15-1]
NP_001165946.1. NM_001172475.1. [Q8CI15-3]
NP_035581.1. NM_011451.3. [Q8CI15-2]
NP_079643.2. NM_025367.6. [Q8CI15-1]
XP_006532733.1. XM_006532670.2. [Q8CI15-3]
XP_006532734.1. XM_006532671.2. [Q8CI15-3]
XP_006532735.1. XM_006532672.2. [Q8CI15-3]
XP_006532736.1. XM_006532673.2. [Q8CI15-1]
UniGeneiMm.20944.

3D structure databases

ProteinModelPortaliQ8CI15.
SMRiQ8CI15. Positions 7-361.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8CI15. 3 interactions.
STRINGi10090.ENSMUSP00000131010.

Chemistry

BindingDBiQ8CI15.
ChEMBLiCHEMBL2401605.

PTM databases

PhosphoSiteiQ8CI15.

Proteomic databases

PaxDbiQ8CI15.
PRIDEiQ8CI15.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000063396; ENSMUSP00000064743; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000063446; ENSMUSP00000067865; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000100201; ENSMUSP00000097775; ENSMUSG00000061878. [Q8CI15-3]
ENSMUST00000106386; ENSMUSP00000101994; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000106387; ENSMUSP00000101995; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000106388; ENSMUSP00000101996; ENSMUSG00000061878. [Q8CI15-1]
ENSMUST00000141798; ENSMUSP00000131010; ENSMUSG00000061878. [Q8CI15-2]
GeneIDi20698.
KEGGimmu:20698.
UCSCiuc007mlg.2. mouse. [Q8CI15-3]
uc007mlh.2. mouse. [Q8CI15-1]
uc007mll.2. mouse. [Q8CI15-2]

Organism-specific databases

CTDi8877.
MGIiMGI:1316649. Sphk1.

Phylogenomic databases

eggNOGiCOG1597.
GeneTreeiENSGT00690000101761.
HOGENOMiHOG000111460.
HOVERGENiHBG054796.
InParanoidiQ8CI15.
KOiK04718.
OMAiLEREDWS.
OrthoDBiEOG7PCJGK.
PhylomeDBiQ8CI15.
TreeFamiTF354296.

Enzyme and pathway databases

BRENDAi2.7.1.91. 3474.
ReactomeiREACT_275351. Association of TriC/CCT with target proteins during biosynthesis.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_335233. Sphingolipid de novo biosynthesis.

Miscellaneous databases

NextBioi299241.
PROiQ8CI15.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CI15.
ExpressionAtlasiQ8CI15. baseline and differential.
GenevisibleiQ8CI15. MM.

Family and domain databases

InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
IPR016064. NAD/diacylglycerol_kinase.
[Graphical view]
PfamiPF00781. DAGK_cat. 1 hit.
[Graphical view]
SMARTiSM00046. DAGKc. 1 hit.
[Graphical view]
SUPFAMiSSF111331. SSF111331. 2 hits.
PROSITEiPS50146. DAGK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and functional characterization of murine sphingosine kinase."
    Kohama T., Olivera A., Edsall L., Nagiec M.M., Dickson R., Spiegel S.
    J. Biol. Chem. 273:23722-23728(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  2. Thompson D., Pyne S.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J and NOD.
    Tissue: Placenta.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Kidney.
  6. "Aminoacylase 1 is a sphingosine kinase 1-interacting protein."
    Maceyka M., Nava V.E., Milstien S., Spiegel S.
    FEBS Lett. 568:30-34(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ACY1.

Entry informationi

Entry nameiSPHK1_MOUSE
AccessioniPrimary (citable) accession number: Q8CI15
Secondary accession number(s): O88886, Q3U2E3, Q91ZN3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: March 1, 2003
Last modified: June 24, 2015
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Sphingosine 1-phosphate stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.