Q9NYA1 (SPHK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sphingosine kinase 1
Short name=SK 1
Short name=SPK 1
EC=2.7.1.91

Gene names

Name:	SPHK1
Synonyms:	SPHK, SPK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	384 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-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol. Ref.11
Catalytic activity	ATP + sphinganine = ADP + sphinganine 1-phosphate. Ref.2 Ref.11 ATP + sphingosine = ADP + sphingosine 1-phosphate. Ref.2 Ref.11
Cofactor	Magnesium. Ref.3
Subunit structure	Interacts with ACY1 By similarity. Binds to calmodulin. Interacts with SPHKAP. Ref.8
Subcellular location	Cytoplasm. Nucleus Ref.9.
Tissue specificity	Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Ref.2
Miscellaneous	Sphingosine 1-phosphate stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling.
Sequence similarities	Contains 1 DAGKc domain.
Biophysicochemical properties	Kinetic parameters: KM=14 µM for sphingosine Ref.3 KM=20 µM for dihydrosphingosine KM=77 µM for ATP pH dependence: Optimum pH is 7.4.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	'de novo' posttranslational protein folding Traceable author statement. Source: Reactome activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro anti-apoptosis Traceable author statement Ref.3. Source: UniProtKB calcium-mediated signaling Inferred from direct assay Ref.3. Source: UniProtKB positive regulation of NF-kappaB import into nucleus Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of angiogenesis Inferred from direct assay. Source: UniProtKB positive regulation of cell growth Inferred from direct assay. Source: UniProtKB positive regulation of cell migration Inferred from direct assay. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from direct assay. Source: MGI positive regulation of mitotic cell cycle Inferred from direct assay. Source: UniProtKB positive regulation of protein ubiquitination Inferred from direct assay Ref.11. Source: UniProtKB positive regulation of smooth muscle contraction Inferred from direct assay. Source: UniProtKB regulation of tumor necrosis factor-mediated signaling pathway Inferred from direct assay Ref.11. Source: UniProtKB sphingoid catabolic process Non-traceable author statement Ref.1. Source: UniProtKB sphingosine metabolic process Inferred from direct assay Ref.11. Source: UniProtKB
Cellular component	cytosol Traceable author statement Ref.1. Source: UniProtKB membrane fraction Traceable author statement Ref.1. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: BHF-UCL soluble fraction Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB D-erythro-sphingosine kinase activity Inferred from direct assay Ref.1Ref.11. Source: UniProtKB DNA binding Inferred from direct assay. Source: MGI calmodulin binding Inferred from direct assay Ref.3. Source: UniProtKB diacylglycerol kinase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from direct assay Ref.3. Source: UniProtKB protein phosphatase 2A binding Inferred from physical interaction. Source: BHF-UCL sphinganine kinase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EEF1A1	P68104	2	EBI-985303,EBI-352162
FHL2	Q14192	7	EBI-985303,EBI-701903
SPHKAP	Q2M3C7	4	EBI-985303,EBI-1803914

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NYA1-1) 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: Q9NYA1-2) The sequence of this isoform differs from the canonical sequence as follows:      1-1: M → MSAQVLGFLR...WQREPRVEVM
Sequence annotation (Features)
	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
	Natural variant	34	1	A → T. Corresponds to variant rs346803 [ dbSNP | Ensembl ].

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 384	384	Sphingosine kinase 1		PRO_0000181357
Regions
	Domain	12 – 159	148	DAGKc
	Motif	147 – 155	9	Nuclear export signal 1
	Motif	161 – 169	9	Nuclear export signal 2
Amino acid modifications
	Modified residue	193	1	Phosphothreonine Ref.10
	Modified residue	225	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	1	1	M → MSAQVLGFLRSWTPLPLAAP RGPAAAGNDAGAPAATAPGG EGEPHSRPCDARLGSTDKEL KAGAAATGSAPTAPGTPWQR EPRVEVM in isoform 2.		VSP_035453
Experimental info
	Mutagenesis	82	1	G → D: Loss of enzyme activity. Ref.11
	Sequence conflict	6	1	Missing in CAB92131. Ref.4
	Sequence conflict	11 – 15	5	LPRPC → ARL in CAB92131. Ref.4
	Sequence conflict	114 – 115	2	NA → KP in CAB92131. Ref.4
	Sequence conflict	251	1	V → M in AAF73423. Ref.2
	Sequence conflict	260	1	V → I in AAF73423. Ref.2
	Sequence conflict	302	1	L → F in AAF73423. Ref.2
	Sequence conflict	325	1	V → G in CAB92131. Ref.4
	Sequence conflict	337	1	V → M in AAG01980. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: EB04A7F2034C2DB0	FASTA	384	42,518
	10 20 30 40 50 60 MDPAGGPRGV LPRPCRVLVL LNPRGGKGKA LQLFRSHVQP LLAEAEISFT LMLTERRNHA 70 80 90 100 110 120 RELVRSEELG RWDALVVMSG DGLMHEVVNG LMERPDWETA IQKPLCSLPA GSGNALAASL 130 140 150 160 170 180 NHYAGYEQVT NEDLLTNCTL LLCRRLLSPM NLLSLHTASG LRLFSVLSLA WGFIADVDLE 190 200 210 220 230 240 SEKYRRLGEM RFTLGTFLRL AALRTYRGRL AYLPVGRVGS KTPASPVVVQ QGPVDAHLVP 250 260 270 280 290 300 LEEPVPSHWT VVPDEDFVLV LALLHSHLGS EMFAAPMGRC AAGVMHLFYV RAGVSRAMLL 310 320 330 340 350 360 RLFLAMEKGR HMEYECPYLV YVPVVAFRLE PKDGKGVFAV DGELMVSEAV QGQVHPNYFW 370 380 MVSGCVEPPP SWKPQQMPPP EEPL
	Isoform 2 [UniParc]. Checksum: F6BF2D324E12CFC0	FASTA	470	51,054
	10 20 30 40 50 60 MSAQVLGFLR SWTPLPLAAP RGPAAAGNDA GAPAATAPGG EGEPHSRPCD ARLGSTDKEL 70 80 90 100 110 120 KAGAAATGSA PTAPGTPWQR EPRVEVMDPA GGPRGVLPRP CRVLVLLNPR GGKGKALQLF 130 140 150 160 170 180 RSHVQPLLAE AEISFTLMLT ERRNHARELV RSEELGRWDA LVVMSGDGLM HEVVNGLMER 190 200 210 220 230 240 PDWETAIQKP LCSLPAGSGN ALAASLNHYA GYEQVTNEDL LTNCTLLLCR RLLSPMNLLS 250 260 270 280 290 300 LHTASGLRLF SVLSLAWGFI ADVDLESEKY RRLGEMRFTL GTFLRLAALR TYRGRLAYLP 310 320 330 340 350 360 VGRVGSKTPA SPVVVQQGPV DAHLVPLEEP VPSHWTVVPD EDFVLVLALL HSHLGSEMFA 370 380 390 400 410 420 APMGRCAAGV MHLFYVRAGV SRAMLLRLFL AMEKGRHMEY ECPYLVYVPV VAFRLEPKDG 430 440 450 460 470 KGVFAVDGEL MVSEAVQGQV HPNYFWMVSG CVEPPPSWKP QQMPPPEEPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution." Melendez A.J., Carlos-Dias E., Gosink M., Allen J.M., Takacs L. Gene 251:19-26(2000) [PubMed: 10863092] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Functional characterization of human sphingosine kinase-1." Nava V.E., Lacana' E., Poulton S., Liu H., Sugiura M., Kono K., Milstien S., Kohama T., Spiegel S. FEBS Lett. 473:81-84(2000) [PubMed: 10802064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, TISSUE SPECIFICITY.
[3]	"Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes." Pitson S.M., D'Andrea R.J., Vandeleur L., Moretti P.A.B., Xia P., Gamble J.R., Vadas M.A., Wattenberg B.W. Biochem. J. 350:429-441(2000) [PubMed: 10947957] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
[4]	Van Veldhoven P.P., Gijsbers S. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Mammary gland, Ovary and Testis.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Blood and Skin.
[8]	"Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity." Lacana E., Maceyka M., Milstien S., Spiegel S. J. Biol. Chem. 277:32947-32953(2002) [PubMed: 12080051] [Abstract] Cited for: INTERACTION WITH SPHKAP.
[9]	"Identification of functional nuclear export sequences in human sphingosine kinase 1." Inagaki Y., Li P.Y., Wada A., Mitsutake S., Igarashi Y. Biochem. Biophys. Res. Commun. 311:168-173(2003) [PubMed: 14575709] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNALS.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2." Alvarez S.E., Harikumar K.B., Hait N.C., Allegood J., Strub G.M., Kim E.Y., Maceyka M., Jiang H., Luo C., Kordula T., Milstien S., Spiegel S. Nature 465:1084-1088(2010) [PubMed: 20577214] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLY-82, PHOSPHORYLATION AT SER-225.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF266756 mRNA. Translation: AAF73470.1. AF238083 mRNA. Translation: AAF73423.1. AF200328 mRNA. Translation: AAG01980.1. AK023393 mRNA. Translation: BAB14558.1. AK292294 mRNA. Translation: BAF84983.1. AK022402 mRNA. Translation: BAB14028.1. AJ245504 mRNA. Translation: CAB92131.1. CH471099 Genomic DNA. Translation: EAW89392.1. BC014439 mRNA. Translation: AAH14439.1. BC030553 mRNA. Translation: AAH30553.1.
IPI	IPI00182048. IPI00790290.
RefSeq	NP_001136073.1. NM_001142601.1. NP_001136074.1. NM_001142602.1. NP_068807.2. NM_021972.3. NP_892010.2. NM_182965.2.
UniGene	Hs.68061.
3D structure databases
ProteinModelPortal	Q9NYA1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NYA1. 5 interactions.
MINT	MINT-226199.
STRING	Q9NYA1.
PTM databases
PhosphoSite	Q9NYA1.
Polymorphism databases
DMDM	17369329.
Proteomic databases
PRIDE	Q9NYA1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323374; ENSP00000313681; ENSG00000176170. ENST00000392496; ENSP00000376285; ENSG00000176170.
GeneID	8877.
KEGG	hsa:8877.
UCSC	uc002jrf.1. human.
Organism-specific databases
CTD	8877.
GeneCards	GC17P074380.
H-InvDB	HIX0022906.
HGNC	HGNC:11240. SPHK1.
HPA	HPA022829. HPA028761.
MIM	603730. gene.
neXtProt	NX_Q9NYA1.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000063185.
HOVERGEN	HBG054796.
InParanoid	Q9NYA1.
OrthoDB	EOG4ZW5B2.
PhylomeDB	Q9NYA1.
Enzyme and pathway databases
BRENDA	2.7.1.91. 2681.
Pathway_Interaction_DB	fcer1pathway. Fc-epsilon receptor I signaling in mast cells. pdgfrbpathway. PDGFR-beta signaling pathway. s1p_s1p1_pathway. S1P1 pathway. s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway.
Reactome	REACT_17015. Metabolism of proteins. REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9NYA1.
Bgee	Q9NYA1.
CleanEx	HS_SPHK1.
Genevestigator	Q9NYA1.
GermOnline	ENSG00000176170. Homo sapiens.
Family and domain databases
InterPro	IPR001206. Diacylglycerol_kinase_cat_dom. [Graphical view]
KO	K04718.
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
SOURCE	Search...

Entry information

Entry name

SPHK1_HUMAN

Accession

Primary (citable) accession number: Q9NYA1
Secondary accession number(s): Q8N632 , Q9HD92, Q9NY70, Q9NYL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2001
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 99 of the entry and version 1 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.