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Q9NRA0 (SPHK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sphingosine kinase 2

Short name=SK 2
Short name=SPK 2
EC=2.7.1.91
Gene names
Name:SPHK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length654 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides. Ref.9

Catalytic activity

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

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

Cofactor

Magnesium By similarity.

Enzyme regulation

Inhibited by sulfatide. Ref.9

Subcellular location

Isoform 1: Cytoplasm. Membrane Ref.7 Ref.9.

Isoform 2: Lysosome membrane Ref.7 Ref.9.

Sequence similarities

Contains 1 DAGKc domain.

Biophysicochemical properties

Kinetic parameters:

KM=3.4 µM for sphingosine Ref.1

pH dependence:

Optimum pH is 7.5.

Ontologies

Keywords
   Cellular componentCytoplasm
Lysosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood vessel development

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Non-traceable author statement Ref.1. Source: UniProtKB

lipid phosphorylation

Non-traceable author statement Ref.1. Source: GOC

negative regulation of apoptotic process

Non-traceable author statement Ref.1. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

protein kinase C-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

small molecule metabolic process

Traceable author statement. Source: Reactome

sphinganine-1-phosphate biosynthetic process

Non-traceable author statement Ref.1. Source: UniProtKB

sphingolipid biosynthetic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

sphingosine metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from direct assay Ref.1. Source: UniProtKB

lysosomal membrane

Inferred from direct assay Ref.7. Source: UniProtKB

membrane

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

D-erythro-sphingosine kinase activity

Inferred from electronic annotation. Source: Ensembl

NAD+ kinase activity

Inferred from electronic annotation. Source: InterPro

Ras GTPase binding

Non-traceable author statement PubMed 12391145. Source: UniProtKB

diacylglycerol kinase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 11777919. Source: UniProtKB

sphinganine kinase activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9NRA0-1)

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.
Isoform 2 (identifier: Q9NRA0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
Isoform 3 (identifier: Q9NRA0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     292-390: FEPALGLDLL...ATVEPASPTP → PREDSDSSTS...NVFICKKKKK
Isoform 4 (identifier: Q9NRA0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     13-71: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q9NRA0-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNGHLEAEEQQD → MIGCLHARVS...NSHPFSPPFP
     640-654: GTLLTGPPGCPGREP → ARGRTQTPALPAAPALYGRQPGAAHGLQPVCQGAALFFHNSWLWGSQDLFRIVLTEAVGG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 654654Sphingosine kinase 2
PRO_0000181358

Regions

Domain178 – 325148DAGKc
Nucleotide binding188 – 1903ATP By similarity
Nucleotide binding220 – 2245ATP By similarity
Nucleotide binding277 – 2793ATP By similarity
Nucleotide binding622 – 6243ATP By similarity
Region1 – 175175Required for binding to sulfatide and phosphoinositides and for membrane localization
Region245 – 2484Substrate binding By similarity

Sites

Active site2471Proton donor/acceptor By similarity
Binding site2521ATP By similarity
Binding site3441Substrate By similarity
Binding site3511ATP By similarity
Binding site3571ATP By similarity

Natural variations

Alternative sequence1 – 3636Missing in isoform 2 and isoform 3.
VSP_006217
Alternative sequence1 – 1212MNGHL…EEQQD → MIGCLHARVSGPLWDAGLCP ASSRSAHTCLSLSVSDAPVS PATAPHCLLLSTAPAPPCPC HGVLNSHPFSPPFP in isoform 5.
VSP_047721
Alternative sequence13 – 7159Missing in isoform 4.
VSP_046910
Alternative sequence292 – 39099FEPAL…ASPTP → PREDSDSSTSSSACPLWTTA RSCPRAAASMPGSCPLLPQQ LALGFSRFIQDRVNGGGGRI GSLTCRGHTQRTLPAPAREG GGSLFLKNINVFICKKKKK in isoform 3.
VSP_006218
Alternative sequence640 – 65415GTLLT…PGREP → ARGRTQTPALPAAPALYGRQ PGAAHGLQPVCQGAALFFHN SWLWGSQDLFRIVLTEAVGG in isoform 5.
VSP_047722
Natural variant6521R → Q.
Corresponds to variant rs11881285 [ dbSNP | Ensembl ].
VAR_060112

Experimental info

Sequence conflict491P → S in CAB66636. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 26, 2002. Version 2.
Checksum: F73FFCEC930DA50F

FASTA65469,217
        10         20         30         40         50         60 
MNGHLEAEEQ QDQRPDQELT GSWGHGPRST LVRAKAMAPP PPPLAASTPL LHGEFGSYPA 

        70         80         90        100        110        120 
RGPRFALTLT SQALHIQRLR PKPEARPRGG LVPLAEVSGC CTLRSRSPSD SAAYFCIYTY 

       130        140        150        160        170        180 
PRGRRGARRR ATRTFRADGA ATYEENRAEA QRWATALTCL LRGLPLPGDG EITPDLLPRP 

       190        200        210        220        230        240 
PRLLLLVNPF GGRGLAWQWC KNHVLPMISE AGLSFNLIQT ERQNHARELV QGLSLSEWDG 

       250        260        270        280        290        300 
IVTVSGDGLL HEVLNGLLDR PDWEEAVKMP VGILPCGSGN ALAGAVNQHG GFEPALGLDL 

       310        320        330        340        350        360 
LLNCSLLLCR GGGHPLDLLS VTLASGSRCF SFLSVAWGFV SDVDIQSERF RALGSARFTL 

       370        380        390        400        410        420 
GTVLGLATLH TYRGRLSYLP ATVEPASPTP AHSLPRAKSE LTLTPDPAPP MAHSPLHRSV 

       430        440        450        460        470        480 
SDLPLPLPQP ALASPGSPEP LPILSLNGGG PELAGDWGGA GDAPLSPDPL LSSPPGSPKA 

       490        500        510        520        530        540 
ALHSPVSEGA PVIPPSSGLP LPTPDARVGA STCGPPDHLL PPLGTPLPPD WVTLEGDFVL 

       550        560        570        580        590        600 
MLAISPSHLG ADLVAAPHAR FDDGLVHLCW VRSGISRAAL LRLFLAMERG SHFSLGCPQL 

       610        620        630        640        650 
GYAAARAFRL EPLTPRGVLT VDGEQVEYGP LQAQMHPGIG TLLTGPPGCP GREP 

« Hide

Isoform 2 [UniParc].

Checksum: 1A5B06BCB6F93F1F
Show »

FASTA61865,205
Isoform 3 [UniParc].

Checksum: D934F61C0A69EDAE
Show »

FASTA61865,170
Isoform 4 [UniParc].

Checksum: C24AC949EEEA059B
Show »

FASTA59562,986
Isoform 5 [UniParc].

Checksum: A52BF3441102A3D3
Show »

FASTA76180,205

References

« Hide 'large scale' references
[1]"Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform."
Liu H., Sugiura M., Nava V.E., Edsall L.C., Kono K., Poulton S., Milstien S., Kohama T., Spiegel S.
J. Biol. Chem. 275:19513-19520(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[2]"Variant of human sphingosine kinase-2 (SPHK2)."
Alemany R., Ruemenapp U., van Koppen C.J., Danneberg K., Meyer zu Heringdorf D., Jakobs K.H.
Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[3]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-354 (ISOFORM 3).
Tissue: Carcinoma and Prostate.
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1 AND 2).
Tissue: Eye and Lymph.
[7]"Integral and associated lysosomal membrane proteins."
Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A.
Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Placenta.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A lipid binding domain in sphingosine kinase 2."
Don A.S., Rosen H.
Biochem. Biophys. Res. Commun. 380:87-92(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, REGION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF245447 mRNA. Translation: AAF74124.1.
EF107108 mRNA. Translation: ABK81123.1.
AL136701 mRNA. Translation: CAB66636.1.
AK000599 mRNA. Translation: BAA91280.1.
AK300541 mRNA. Translation: BAG62249.1.
AC022154 Genomic DNA. No translation available.
BC006161 mRNA. Translation: AAH06161.1.
BC010671 mRNA. Translation: AAH10671.1.
CCDSCCDS12727.1. [Q9NRA0-1]
CCDS59404.1. [Q9NRA0-4]
CCDS59405.1. [Q9NRA0-2]
RefSeqNP_001191087.1. NM_001204158.2. [Q9NRA0-4]
NP_001191088.1. NM_001204159.2. [Q9NRA0-1]
NP_001191089.1. NM_001204160.2. [Q9NRA0-2]
NP_064511.2. NM_020126.4. [Q9NRA0-1]
XP_006723354.1. XM_006723291.1. [Q9NRA0-1]
XP_006723355.1. XM_006723292.1. [Q9NRA0-2]
XP_006723356.1. XM_006723293.1. [Q9NRA0-4]
UniGeneHs.528006.

3D structure databases

ProteinModelPortalQ9NRA0.
SMRQ9NRA0. Positions 176-406, 514-637.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121208. 2 interactions.
IntActQ9NRA0. 5 interactions.
STRING9606.ENSP00000245222.

Chemistry

BindingDBQ9NRA0.
ChEMBLCHEMBL3023.
GuidetoPHARMACOLOGY2205.

PTM databases

PhosphoSiteQ9NRA0.

Polymorphism databases

DMDM22001996.

Proteomic databases

MaxQBQ9NRA0.
PaxDbQ9NRA0.
PRIDEQ9NRA0.

Protocols and materials databases

DNASU56848.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245222; ENSP00000245222; ENSG00000063176. [Q9NRA0-1]
ENST00000443164; ENSP00000413369; ENSG00000063176. [Q9NRA0-5]
ENST00000598088; ENSP00000469158; ENSG00000063176. [Q9NRA0-1]
ENST00000599748; ENSP00000471205; ENSG00000063176. [Q9NRA0-2]
ENST00000600537; ENSP00000470092; ENSG00000063176. [Q9NRA0-4]
GeneID56848.
KEGGhsa:56848.
UCSCuc002pjr.3. human. [Q9NRA0-1]
uc002pju.3. human. [Q9NRA0-3]

Organism-specific databases

CTD56848.
GeneCardsGC19P049122.
HGNCHGNC:18859. SPHK2.
MIM607092. gene.
neXtProtNX_Q9NRA0.
PharmGKBPA38719.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1597.
HOGENOMHOG000111460.
HOVERGENHBG054796.
InParanoidQ9NRA0.
KOK04718.
OrthoDBEOG7PCJGK.
PhylomeDBQ9NRA0.
TreeFamTF354296.

Enzyme and pathway databases

BRENDA2.7.1.91. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NRA0.
BgeeQ9NRA0.
GenevestigatorQ9NRA0.

Family and domain databases

InterProIPR016064. ATP-NAD_kinase_PpnK-typ.
IPR001206. Diacylglycerol_kinase_cat_dom.
[Graphical view]
PfamPF00781. DAGK_cat. 1 hit.
[Graphical view]
SMARTSM00046. DAGKc. 1 hit.
[Graphical view]
SUPFAMSSF111331. SSF111331. 2 hits.
PROSITEPS50146. DAGK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSPHK2. human.
GeneWikiSPHK2.
GenomeRNAi56848.
NextBio35460299.
PROQ9NRA0.
SOURCESearch...

Entry information

Entry nameSPHK2_HUMAN
AccessionPrimary (citable) accession number: Q9NRA0
Secondary accession number(s): A0T4C8 expand/collapse secondary AC list , B4DU87, Q9BRN1, Q9H0Q2, Q9NWU7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 24, 2001
Last sequence update: July 26, 2002
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM