Reviewed, UniProtKB/Swiss-Prot Q9NYA1 (SPHK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Sphingosine kinase 1
      Short name=SPK 1
      Short name=SK 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.
Sequence processing	The displayed sequence is not processed.
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.
Catalytic activity	ATP + sphinganine = ADP + sphinganine 1-phosphate. Ref.2 ATP + sphingosine = ADP + sphingosine 1-phosphate. Ref.2
Cofactor	Magnesium. Ref.3
Subunit structure	Interacts with ACY1 By similarity. Binds to calmodulin. Interacts with SPHKAP.
Tissue specificity	Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Ref.2
Sequence similarities	Contains 1 DAGKc domain.
biophysicochemical properties	Kinetic parameters: KM=14 µM for sphingosine KM=20 µM for dihydrosphingosine KM=77 µM for ATP pH dependence: Optimum pH is 7.4.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro anti-apoptosis Ref.3 Traceable author statement. Source: UniProtKB calcium-mediated signaling Ref.3 Inferred from direct assay. 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 smooth muscle contraction Inferred from direct assay. Source: UniProtKB sphingoid catabolic process Ref.1 Non-traceable author statement. Source: UniProtKB sphingosine metabolic process Traceable author statement. Source: ProtInc
Cellular component	cytosol Ref.1 Traceable author statement. Source: UniProtKB membrane fraction Ref.1 Traceable author statement. Source: UniProtKB soluble fraction Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB D-erythro-sphingosine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB DNA binding Inferred from direct assay. Source: MGI calmodulin binding Ref.3 Inferred from direct assay. Source: UniProtKB diacylglycerol kinase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Ref.3 Inferred from direct assay. Source: UniProtKB sphinganine kinase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FHL2	Q14192	4	EBI-985303,EBI-701903
FYN	P06241	1	EBI-985303,EBI-515315
SPHKAP	Q2M3C7	2	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
Molecule processing
	Chain	1 – 384	384	Sphingosine kinase 1		PRO_0000181357
Regions
	Domain	16 – 153	138	DAGKc
Amino acid modifications
	Modified residue	193	1	Phosphothreonine Ref.9
Natural variations
	Alternative sequence	1	1	M → MSAQVLGFLRSWTPLPLAAP RGPAAAGNDAGAPTATAPGG EGEPHSRPCDARLGSTDKEL KAGAAATGSAPTAPGTPWQR EPRVEVM in isoform 2.		VSP_035453
Experimental info
	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. Checksum: 5172E93A38C7CC17	FASTA	470	51,084
	10 20 30 40 50 60 MSAQVLGFLR SWTPLPLAAP RGPAAAGNDA GAPTATAPGG 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]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. NP_001136074.1. NP_068807.2. NP_892010.2.
UniGene	Hs.68061
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NYA1. 3 interactions.
PTM databases
PhosphoSite	Q9NYA1.
Genome annotation databases
Ensembl	ENSG00000176170. Homo sapiens. [Contig view]
GeneID	8877.
Organism-specific databases
GeneCards	GC17P071890.
H-InvDB	HIX0022906.
HGNC	HGNC:11240. SPHK1.
MIM	603730. gene.
PharmGKB	PA36070.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9NYA1.
Enzyme and pathway databases
BRENDA	2.7.1.91. 247.
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.
Gene expression databases
ArrayExpress	Q9NYA1.
Bgee	Q9NYA1.
CleanEx	HS_SPHK1.
GermOnline	ENSG00000176170. Homo sapiens.
Family and domain databases
InterPro	IPR001206. Diacylglycerol_kinase_cat. [Graphical view]
Pfam	PF00781. DAGK_cat. 1 hit. [Graphical view]
ProDom	PD005043. DAGKc. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00046. DAGKc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	April 14, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)