Q9NRA0 (SPHK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine kinase 2
Short name=SK 2
Short name=SPK 2
EC=2.7.1.91

Gene names

Name:

SPHK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	654 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7
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.7
Subcellular location	Isoform 1: Cytoplasm. Membrane Ref.5 Ref.7. Isoform 2: Lysosome membrane Ref.5 Ref.7.
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 component	Cytoplasm Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cell proliferation Non-traceable author statement Ref.1. Source: UniProtKB negative regulation of apoptotic process Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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 sphingosine metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW D-erythro-sphingosine kinase activity Inferred from electronic annotation. Source: Compara Ras GTPase binding Non-traceable author statement PubMed 12391145. Source: UniProtKB diacylglycerol kinase activity Inferred from electronic annotation. Source: InterPro sphinganine kinase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 654	654	Sphingosine kinase 2		PRO_0000181358
Regions
	Domain	178 – 325	148	DAGKc
	Region	1 – 175	175	Required for binding to sulfatide and phosphoinositides and for membrane localization
Amino acid modifications
	Modified residue	399	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 36	36	Missing in isoform 2 and isoform 3.		VSP_006217
	Alternative sequence	292 – 390	99	FEPAL…ASPTP → PREDSDSSTSSSACPLWTTA RSCPRAAASMPGSCPLLPQQ LALGFSRFIQDRVNGGGGRI GSLTCRGHTQRTLPAPAREG GGSLFLKNINVFICKKKKK in isoform 3.		VSP_006218
	Natural variant	652	1	R → Q. Corresponds to variant rs11881285 [ dbSNP | Ensembl ].		VAR_060112
Experimental info
	Sequence conflict	49	1	P → S in CAB66636. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 26, 2002. Version 2. Checksum: F73FFCEC930DA50F	FASTA	654	69,217
	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
	Isoform 2 [UniParc]. Checksum: 1A5B06BCB6F93F1F	FASTA	618	65,205
	10 20 30 40 50 60 MAPPPPPLAA STPLLHGEFG SYPARGPRFA LTLTSQALHI QRLRPKPEAR PRGGLVPLAE 70 80 90 100 110 120 VSGCCTLRSR SPSDSAAYFC IYTYPRGRRG ARRRATRTFR ADGAATYEEN RAEAQRWATA 130 140 150 160 170 180 LTCLLRGLPL PGDGEITPDL LPRPPRLLLL VNPFGGRGLA WQWCKNHVLP MISEAGLSFN 190 200 210 220 230 240 LIQTERQNHA RELVQGLSLS EWDGIVTVSG DGLLHEVLNG LLDRPDWEEA VKMPVGILPC 250 260 270 280 290 300 GSGNALAGAV NQHGGFEPAL GLDLLLNCSL LLCRGGGHPL DLLSVTLASG SRCFSFLSVA 310 320 330 340 350 360 WGFVSDVDIQ SERFRALGSA RFTLGTVLGL ATLHTYRGRL SYLPATVEPA SPTPAHSLPR 370 380 390 400 410 420 AKSELTLTPD PAPPMAHSPL HRSVSDLPLP LPQPALASPG SPEPLPILSL NGGGPELAGD 430 440 450 460 470 480 WGGAGDAPLS PDPLLSSPPG SPKAALHSPV SEGAPVIPPS SGLPLPTPDA RVGASTCGPP 490 500 510 520 530 540 DHLLPPLGTP LPPDWVTLEG DFVLMLAISP SHLGADLVAA PHARFDDGLV HLCWVRSGIS 550 560 570 580 590 600 RAALLRLFLA MERGSHFSLG CPQLGYAAAR AFRLEPLTPR GVLTVDGEQV EYGPLQAQMH 610 PGIGTLLTGP PGCPGREP
	Isoform 3 [UniParc]. Checksum: D934F61C0A69EDAE	FASTA	618	65,170
	10 20 30 40 50 60 MAPPPPPLAA STPLLHGEFG SYPARGPRFA LTLTSQALHI QRLRPKPEAR PRGGLVPLAE 70 80 90 100 110 120 VSGCCTLRSR SPSDSAAYFC IYTYPRGRRG ARRRATRTFR ADGAATYEEN RAEAQRWATA 130 140 150 160 170 180 LTCLLRGLPL PGDGEITPDL LPRPPRLLLL VNPFGGRGLA WQWCKNHVLP MISEAGLSFN 190 200 210 220 230 240 LIQTERQNHA RELVQGLSLS EWDGIVTVSG DGLLHEVLNG LLDRPDWEEA VKMPVGILPC 250 260 270 280 290 300 GSGNALAGAV NQHGGPREDS DSSTSSSACP LWTTARSCPR AAASMPGSCP LLPQQLALGF 310 320 330 340 350 360 SRFIQDRVNG GGGRIGSLTC RGHTQRTLPA PAREGGGSLF LKNINVFICK KKKKAHSLPR 370 380 390 400 410 420 AKSELTLTPD PAPPMAHSPL HRSVSDLPLP LPQPALASPG SPEPLPILSL NGGGPELAGD 430 440 450 460 470 480 WGGAGDAPLS PDPLLSSPPG SPKAALHSPV SEGAPVIPPS SGLPLPTPDA RVGASTCGPP 490 500 510 520 530 540 DHLLPPLGTP LPPDWVTLEG DFVLMLAISP SHLGADLVAA PHARFDDGLV HLCWVRSGIS 550 560 570 580 590 600 RAALLRLFLA MERGSHFSLG CPQLGYAAAR AFRLEPLTPR GVLTVDGEQV EYGPLQAQMH 610 PGIGTLLTGP PGCPGREP

References

	« Hide 'large scale' referencesShow '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]	"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. , 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.
[3]	"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.
[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. , 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] OF 1-354 (ISOFORM 3). Tissue: Carcinoma.
[5]	"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], MASS SPECTROMETRY. Tissue: Placenta.
[6]	"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.
[7]	"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. AL136701 mRNA. Translation: CAB66636.1. BC006161 mRNA. Translation: AAH06161.1. BC010671 mRNA. Translation: AAH10671.1. AK000599 mRNA. Translation: BAA91280.1.
IPI	IPI00215795. IPI00215796. IPI00939760.
RefSeq	NP_001191088.1. NM_001204159.2. NP_001191089.1. NM_001204160.2. NP_064511.2. NM_020126.4.
UniGene	Hs.528006.
3D structure databases
ProteinModelPortal	Q9NRA0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NRA0. 5 interactions.
STRING	9606.ENSP00000245222.
PTM databases
PhosphoSite	Q9NRA0.
Polymorphism databases
DMDM	22001996.
Proteomic databases
PaxDb	Q9NRA0.
PRIDE	Q9NRA0.
Protocols and materials databases
DNASU	56848.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245222; ENSP00000245222; ENSG00000063176. ENST00000598088; ENSP00000469158; ENSG00000063176. ENST00000599748; ENSP00000471205; ENSG00000063176.
GeneID	56848.
KEGG	hsa:56848.
UCSC	uc002pjr.3. human. uc002pju.3. human.
Organism-specific databases
CTD	56848.
GeneCards	GC19P049122.
HGNC	HGNC:18859. SPHK2.
MIM	607092. gene.
neXtProt	NX_Q9NRA0.
PharmGKB	PA38719.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1597.
HOGENOM	HOG000111460.
HOVERGEN	HBG054796.
InParanoid	Q9NRA0.
KO	K04718.
OrthoDB	EOG4X0MSG.
PhylomeDB	Q9NRA0.
Enzyme and pathway databases
BRENDA	2.7.1.91. 2681.
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway. il12_2pathway. IL12-mediated signaling events. s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9NRA0.
Bgee	Q9NRA0.
Genevestigator	Q9NRA0.
GermOnline	ENSG00000063176. Homo sapiens.
Family and domain databases
InterPro	IPR001206. Diacylglycerol_kinase_cat_dom. [Graphical view]
Pfam	PF00781. DAGK_cat. 1 hit. [Graphical view]
SMART	SM00046. DAGKc. 1 hit. [Graphical view]
PROSITE	PS50146. DAGK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NRA0.
ChEMBL	CHEMBL3023.
ChiTaRS	SPHK2. human.
GenomeRNAi	56848.
NextBio	62244.
SOURCE	Search...

Entry information

Entry name

SPHK2_HUMAN

Accession

Primary (citable) accession number: Q9NRA0
Secondary accession number(s): Q9BRN1, Q9H0Q2, Q9NWU7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2001
Last sequence update:	July 26, 2002
Last modified:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.