SPHK2

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-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:19168031, PubMed:12954646).

In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219).

In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514).

In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656).

In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110).

In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity).

In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity).

Also involved in the regulation of glucose and lipid metabolism (By similarity).

By similarity6 Publications

Catalytic activityⁱ

Cofactorⁱ

Mg²⁺By similarity

Activity regulationⁱ

Inhibited by sulfatide (PubMed:19168031). Kinase activity is increased by phosphorylation by MAPK2 upon PMA or EGF treatments (PubMed:17311928).2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Length
Active siteⁱ	247	Proton donor/acceptorBy similarity	1
Binding siteⁱ	252	ATPPROSITE-ProRule annotation	1
Binding siteⁱ	344	SubstrateBy similarity	1
Binding siteⁱ	351	ATPPROSITE-ProRule annotation	1
Binding siteⁱ	357	ATPPROSITE-ProRule annotation	1

Regions

Feature key	Position(s)	DescriptionActions	Length
Nucleotide bindingⁱ	188 – 190	ATPPROSITE-ProRule annotation	3
Nucleotide bindingⁱ	220 – 224	ATPPROSITE-ProRule annotation	5
Nucleotide bindingⁱ	277 – 279	ATPPROSITE-ProRule annotation	3
Nucleotide bindingⁱ	622 – 624	ATPPROSITE-ProRule annotation	3

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Transferase
Biological process	Lipid metabolism
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.1.91, 2681
PathwayCommonsⁱ	Q9NRA0
Reactomeⁱ	R-HSA-1660661, Sphingolipid de novo biosynthesis
SignaLinkⁱ	Q9NRA0
SIGNORⁱ	Q9NRA0

Chemistry databases

SwissLipidsⁱ	SLP:000000112

SwissLipidsⁱ

SLP:000000112

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Sphingosine kinase 2Curated (EC:2.7.1.913 Publications) Short name: SK 2 Short name: SPK 2
Gene namesⁱ	Name:SPHK2Imported Synonyms:SK2
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:18859, SPHK2
MIMⁱ	607092, gene
neXtProtⁱ	NX_Q9NRA0
VEuPathDBⁱ	HostDB:ENSG00000063176

Keywords - Cellular componentⁱ

Cytoplasm, Endoplasmic reticulum, Lysosome, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

In patients with Alzheimer's disease brains, may be preferentially localized in the nucleus. Cytosolic expression decrease correlates with the density of amyloid deposits.1 Publication

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	138	D → A: Abolishes cleavage and secretion in apoptotic cells. No effect on kinase activity. 1 Publication	1
Mutagenesisⁱ	212	G → E: Decreases SPP production in nucleus. Abolishes increase of histone acetylation. No effect on association with histone 3. 1 Publication	1
Mutagenesisⁱ	220	T → A: Loss of location to cell membrane. Not secreted. No effect on kinase acitivity. 1 Publication	1
Mutagenesisⁱ	387	S → A: Strongly reduces phosphorylation levels. 1 Publication	1
Mutagenesisⁱ	419 – 421	SVS → AVA: Abolishes nuclear export in response to PMA treatment. 1 Publication	3
Mutagenesisⁱ	423 – 425	LPL → APA: Abolishes nuclear export. 1 Publication	3
Mutagenesisⁱ	437	S → A: Reduces phosphorylation levels. 1 Publication	1
Mutagenesisⁱ	466	S → A: Reduces phosphorylation levels. 1 Publication	1
Mutagenesisⁱ	477	S → A: Reduces phosphorylation levels. 1 Publication	1
Mutagenesisⁱ	552	D → A: No effect on cleavage and secretion in apoptotic cells. No effect on kinase activity. 1 Publication	1
Mutagenesisⁱ	614	T → A: Abolishes phosphorylation. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	56848
Open Targets More...OpenTargetsⁱ	ENSG00000063176
PharmGKBⁱ	PA38719

Miscellaneous databases

Pharosⁱ	Q9NRA0, Tchem

Pharosⁱ

Q9NRA0, Tchem

Chemistry databases

ChEMBLⁱ	CHEMBL3023
Drug and drug target database More...DrugBankⁱ	DB12764, Opaganib
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2205

Genetic variation databases

BioMutaⁱ	SPHK2
DMDMⁱ	22001996

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000181358	1 – 654	Sphingosine kinase 2Add BLAST		654

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	387	Phosphoserine; by MAPKCombined sources1 Publication	1
Modified residueⁱ	393	PhosphoserineBy similarity	1
Modified residueⁱ	399	PhosphoserineCombined sources	1
Modified residueⁱ	419	Phosphoserine; by PKD1 Publication	1
Modified residueⁱ	421	Phosphoserine; by PKD1 Publication	1
Modified residueⁱ	477	PhosphoserineCombined sources	1
Modified residueⁱ	614	Phosphothreonine; by MAPK1 Publication	1

Post-translational modificationⁱ

Phosphorylated by PKD on Ser-419 and Ser-421 upon PMA treatment. Phosphorylation induces export from the nucleus to the cytoplasm (PubMed:17635916). Phosphorylated by MAPK1 and MAPK2 at Ser-387 and Thr-614, phosphorylation is induced by agonists such as EGF and PMA and increases kinase activity (PubMed:17311928).2 Publications

Cleaved by CASP1 in apoptotic cells. The truncated form is released from cells.1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	Q9NRA0
jPOSTⁱ	Q9NRA0
MassIVEⁱ	Q9NRA0
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q9NRA0
PaxDbⁱ	Q9NRA0
PeptideAtlas More...PeptideAtlasⁱ	Q9NRA0
PRIDEⁱ	Q9NRA0
ProteomicsDBⁱ	82315 [Q9NRA0-1] 82316 [Q9NRA0-2] 82317 [Q9NRA0-3] 86

PTM databases

iPTMnetⁱ	Q9NRA0
PhosphoSitePlusⁱ	Q9NRA0

Expressionⁱ

Tissue specificityⁱ

Mainly expressed in adult kidney, liver, and brain (PubMed:10751414). Expressed in cerebral cortex and hippocampus (at protein level) (PubMed:29615132). Isoform 1 is the predominant form expressed in most tissues (PubMed:16103110).3 Publications

Gene expression databases

Bgeeⁱ	ENSG00000063176, Expressed in substantia nigra and 173 other tissues
ExpressionAtlasⁱ	Q9NRA0, baseline and differential
Genevisibleⁱ	Q9NRA0, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000063176, Low tissue specificity

HPAⁱ

ENSG00000063176, Low tissue specificity

Interactionⁱ

Subunit structureⁱ

Interacts with histone H3 (PubMed:19729656).

Interacts with HDAC1, HDAC2, MBD2 and SIN3A (PubMed:19729656).

Interacts with EEF1A1; the interaction enhances SPHK2 kinase activity (PubMed:18263879).

Interacts with PHB2 (By similarity).

By similarity2 Publications

Binary interactionsⁱ

Q9NRA0

With	#Exp.	IntAct
OPTN [Q96CV9]	3	EBI-985324,EBI-748974

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	121208, 19 interactors
IntActⁱ	Q9NRA0, 7 interactors
STRINGⁱ	9606.ENSP00000245222

Chemistry databases

BindingDBⁱ

Q9NRA0

Miscellaneous databases

RNActⁱ	Q9NRA0, protein

RNActⁱ

Q9NRA0, protein

Structureⁱ

3D structure databases

AlphaFoldDBⁱ	Q9NRA0
SMRⁱ	Q9NRA0
ModBaseⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	178 – 325	DAGKcPROSITE-ProRule annotationAdd BLAST		148

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	1 – 175	Required for binding to sulfatide and phosphoinositides and for membrane localizatione1 PublicationAdd BLAST	175
Regionⁱ	1 – 28	DisorderedSequence analysisAdd BLAST	28
Regionⁱ	245 – 248	Substrate bindingBy similarity	4
Regionⁱ	400 – 509	DisorderedSequence analysisAdd BLAST	110

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	122 – 130	Nuclear localization signalBy similarity		9
Motifⁱ	416 – 425	Nuclear export signal1 Publication		10

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	1 – 15	Basic and acidic residuesSequence analysisAdd BLAST		15

Phylogenomic databases

eggNOGⁱ	KOG1116, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000161197
HOGENOMⁱ	CLU_013399_1_1_1
InParanoidⁱ	Q9NRA0
OMAⁱ	EREDGMM
Database of Orthologous Groups More...OrthoDBⁱ	681139at2759
PhylomeDBⁱ	Q9NRA0
TreeFamⁱ	TF354296

Family and domain databases

Gene3Dⁱ	3.40.50.10330, 1 hit
InterProⁱ	View protein in InterPro IPR017438, ATP-NAD_kinase_N IPR001206, Diacylglycerol_kinase_cat_dom IPR016064, NAD/diacylglycerol_kinase_sf IPR045540, YegS/DAGK_C
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00781, DAGK_cat, 1 hit PF19279, YegS_C, 1 hit
SMARTⁱ	View protein in SMART SM00046, DAGKc, 1 hit
SUPFAMⁱ	SSF111331, SSF111331, 1 hit
PROSITEⁱ	View protein in PROSITE PS50146, DAGK, 1 hit

Sequences (5+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

Note: Experimental confirmation may be lacking for some isoforms.

This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: Q9NRA0-1) [UniParc]FASTA Add to basket

Also known as: SK2B, SK2-L1 Publication

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

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        10         20         30         40         50
MNGHLEAEEQ QDQRPDQELT GSWGHGPRST LVRAKAMAPP PPPLAASTPL 
        60         70         80         90        100
LHGEFGSYPA RGPRFALTLT SQALHIQRLR PKPEARPRGG LVPLAEVSGC 
       110        120        130        140        150
CTLRSRSPSD SAAYFCIYTY PRGRRGARRR ATRTFRADGA ATYEENRAEA 
       160        170        180        190        200
QRWATALTCL LRGLPLPGDG EITPDLLPRP PRLLLLVNPF GGRGLAWQWC 
       210        220        230        240        250
KNHVLPMISE AGLSFNLIQT ERQNHARELV QGLSLSEWDG IVTVSGDGLL 
       260        270        280        290        300
HEVLNGLLDR PDWEEAVKMP VGILPCGSGN ALAGAVNQHG GFEPALGLDL 
       310        320        330        340        350
LLNCSLLLCR GGGHPLDLLS VTLASGSRCF SFLSVAWGFV SDVDIQSERF 
       360        370        380        390        400
RALGSARFTL GTVLGLATLH TYRGRLSYLP ATVEPASPTP AHSLPRAKSE 
       410        420        430        440        450
LTLTPDPAPP MAHSPLHRSV SDLPLPLPQP ALASPGSPEP LPILSLNGGG 
       460        470        480        490        500
PELAGDWGGA GDAPLSPDPL LSSPPGSPKA ALHSPVSEGA PVIPPSSGLP 
       510        520        530        540        550
LPTPDARVGA STCGPPDHLL PPLGTPLPPD WVTLEGDFVL MLAISPSHLG 
       560        570        580        590        600
ADLVAAPHAR FDDGLVHLCW VRSGISRAAL LRLFLAMERG SHFSLGCPQL 
       610        620        630        640        650
GYAAARAFRL EPLTPRGVLT VDGEQVEYGP LQAQMHPGIG TLLTGPPGCP 

GREP

Length:654

Mass (Da):69,217

Last modified:July 26, 2002 - v2

Checksum:ⁱF73FFCEC930DA50F

GO

Isoform 2 (identifier: Q9NRA0-2) [UniParc]FASTA Add to basket

Also known as: SK2A, SK2-S1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
1-36: Missing.

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        10         20         30         40         50
MAPPPPPLAA STPLLHGEFG SYPARGPRFA LTLTSQALHI QRLRPKPEAR 
        60         70         80         90        100
PRGGLVPLAE VSGCCTLRSR SPSDSAAYFC IYTYPRGRRG ARRRATRTFR 
       110        120        130        140        150
ADGAATYEEN RAEAQRWATA LTCLLRGLPL PGDGEITPDL LPRPPRLLLL 
       160        170        180        190        200
VNPFGGRGLA WQWCKNHVLP MISEAGLSFN LIQTERQNHA RELVQGLSLS 
       210        220        230        240        250
EWDGIVTVSG DGLLHEVLNG LLDRPDWEEA VKMPVGILPC GSGNALAGAV 
       260        270        280        290        300
NQHGGFEPAL GLDLLLNCSL LLCRGGGHPL DLLSVTLASG SRCFSFLSVA 
       310        320        330        340        350
WGFVSDVDIQ SERFRALGSA RFTLGTVLGL ATLHTYRGRL SYLPATVEPA 
       360        370        380        390        400
SPTPAHSLPR AKSELTLTPD PAPPMAHSPL HRSVSDLPLP LPQPALASPG 
       410        420        430        440        450
SPEPLPILSL NGGGPELAGD WGGAGDAPLS PDPLLSSPPG SPKAALHSPV 
       460        470        480        490        500
SEGAPVIPPS SGLPLPTPDA RVGASTCGPP DHLLPPLGTP LPPDWVTLEG 
       510        520        530        540        550
DFVLMLAISP SHLGADLVAA PHARFDDGLV HLCWVRSGIS RAALLRLFLA 
       560        570        580        590        600
MERGSHFSLG CPQLGYAAAR AFRLEPLTPR GVLTVDGEQV EYGPLQAQMH 
       610 
PGIGTLLTGP PGCPGREP

Show »

Length:618

Mass (Da):65,205

Checksum:ⁱ1A5B06BCB6F93F1F

GO

Isoform 3 (identifier: Q9NRA0-3) [UniParc]FASTA Add to basket

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

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        10         20         30         40         50
MAPPPPPLAA STPLLHGEFG SYPARGPRFA LTLTSQALHI QRLRPKPEAR 
        60         70         80         90        100
PRGGLVPLAE VSGCCTLRSR SPSDSAAYFC IYTYPRGRRG ARRRATRTFR 
       110        120        130        140        150
ADGAATYEEN RAEAQRWATA LTCLLRGLPL PGDGEITPDL LPRPPRLLLL 
       160        170        180        190        200
VNPFGGRGLA WQWCKNHVLP MISEAGLSFN LIQTERQNHA RELVQGLSLS 
       210        220        230        240        250
EWDGIVTVSG DGLLHEVLNG LLDRPDWEEA VKMPVGILPC GSGNALAGAV 
       260        270        280        290        300
NQHGGPREDS DSSTSSSACP LWTTARSCPR AAASMPGSCP LLPQQLALGF 
       310        320        330        340        350
SRFIQDRVNG GGGRIGSLTC RGHTQRTLPA PAREGGGSLF LKNINVFICK 
       360        370        380        390        400
KKKKAHSLPR AKSELTLTPD PAPPMAHSPL HRSVSDLPLP LPQPALASPG 
       410        420        430        440        450
SPEPLPILSL NGGGPELAGD WGGAGDAPLS PDPLLSSPPG SPKAALHSPV 
       460        470        480        490        500
SEGAPVIPPS SGLPLPTPDA RVGASTCGPP DHLLPPLGTP LPPDWVTLEG 
       510        520        530        540        550
DFVLMLAISP SHLGADLVAA PHARFDDGLV HLCWVRSGIS RAALLRLFLA 
       560        570        580        590        600
MERGSHFSLG CPQLGYAAAR AFRLEPLTPR GVLTVDGEQV EYGPLQAQMH 
       610 
PGIGTLLTGP PGCPGREP

Show »

Length:618

Mass (Da):65,170

Checksum:ⁱD934F61C0A69EDAE

GO

Isoform 4 (identifier: Q9NRA0-4) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
13-71: Missing.

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        10         20         30         40         50
MNGHLEAEEQ QDQALHIQRL RPKPEARPRG GLVPLAEVSG CCTLRSRSPS 
        60         70         80         90        100
DSAAYFCIYT YPRGRRGARR RATRTFRADG AATYEENRAE AQRWATALTC 
       110        120        130        140        150
LLRGLPLPGD GEITPDLLPR PPRLLLLVNP FGGRGLAWQW CKNHVLPMIS 
       160        170        180        190        200
EAGLSFNLIQ TERQNHAREL VQGLSLSEWD GIVTVSGDGL LHEVLNGLLD 
       210        220        230        240        250
RPDWEEAVKM PVGILPCGSG NALAGAVNQH GGFEPALGLD LLLNCSLLLC 
       260        270        280        290        300
RGGGHPLDLL SVTLASGSRC FSFLSVAWGF VSDVDIQSER FRALGSARFT 
       310        320        330        340        350
LGTVLGLATL HTYRGRLSYL PATVEPASPT PAHSLPRAKS ELTLTPDPAP 
       360        370        380        390        400
PMAHSPLHRS VSDLPLPLPQ PALASPGSPE PLPILSLNGG GPELAGDWGG 
       410        420        430        440        450
AGDAPLSPDP LLSSPPGSPK AALHSPVSEG APVIPPSSGL PLPTPDARVG 
       460        470        480        490        500
ASTCGPPDHL LPPLGTPLPP DWVTLEGDFV LMLAISPSHL GADLVAAPHA 
       510        520        530        540        550
RFDDGLVHLC WVRSGISRAA LLRLFLAMER GSHFSLGCPQ LGYAAARAFR 
       560        570        580        590 
LEPLTPRGVL TVDGEQVEYG PLQAQMHPGI GTLLTGPPGC PGREP

Show »

Length:595

Mass (Da):62,986

Checksum:ⁱC24AC949EEEA059B

GO

Isoform 5 (identifier: Q9NRA0-5) [UniParc]FASTA Add to basket

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

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        10         20         30         40         50
MIGCLHARVS GPLWDAGLCP ASSRSAHTCL SLSVSDAPVS PATAPHCLLL 
        60         70         80         90        100
STAPAPPCPC HGVLNSHPFS PPFPQRPDQE LTGSWGHGPR STLVRAKAMA 
       110        120        130        140        150
PPPPPLAAST PLLHGEFGSY PARGPRFALT LTSQALHIQR LRPKPEARPR 
       160        170        180        190        200
GGLVPLAEVS GCCTLRSRSP SDSAAYFCIY TYPRGRRGAR RRATRTFRAD 
       210        220        230        240        250
GAATYEENRA EAQRWATALT CLLRGLPLPG DGEITPDLLP RPPRLLLLVN 
       260        270        280        290        300
PFGGRGLAWQ WCKNHVLPMI SEAGLSFNLI QTERQNHARE LVQGLSLSEW 
       310        320        330        340        350
DGIVTVSGDG LLHEVLNGLL DRPDWEEAVK MPVGILPCGS GNALAGAVNQ 
       360        370        380        390        400
HGGFEPALGL DLLLNCSLLL CRGGGHPLDL LSVTLASGSR CFSFLSVAWG 
       410        420        430        440        450
FVSDVDIQSE RFRALGSARF TLGTVLGLAT LHTYRGRLSY LPATVEPASP 
       460        470        480        490        500
TPAHSLPRAK SELTLTPDPA PPMAHSPLHR SVSDLPLPLP QPALASPGSP 
       510        520        530        540        550
EPLPILSLNG GGPELAGDWG GAGDAPLSPD PLLSSPPGSP KAALHSPVSE 
       560        570        580        590        600
GAPVIPPSSG LPLPTPDARV GASTCGPPDH LLPPLGTPLP PDWVTLEGDF 
       610        620        630        640        650
VLMLAISPSH LGADLVAAPH ARFDDGLVHL CWVRSGISRA ALLRLFLAME 
       660        670        680        690        700
RGSHFSLGCP QLGYAAARAF RLEPLTPRGV LTVDGEQVEY GPLQAQMHPG 
       710        720        730        740        750
IARGRTQTPA LPAAPALYGR QPGAAHGLQP VCQGAALFFH NSWLWGSQDL 
       760 
FRIVLTEAVG G

Show »

Length:761

Mass (Da):80,205

Checksum:ⁱA52BF3441102A3D3

GO

Computationally mapped potential isoform sequencesⁱ

There are 7 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

M0R344	M0R344_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	663	Annotation score:
M0R0E9	M0R0E9_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	255	Annotation score:
E9PCV4	E9PCV4_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2 (Sphingosine kinase 2, isoform CRA_e)	SPHK2 hCG_15274	448	Annotation score:
M0QXX5	M0QXX5_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	133	Annotation score:
A0A075B7A1	A0A075B7A1_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	349	Annotation score:
M0QZP3	M0QZP3_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	72	Annotation score:
E7ET12	E7ET12_HUMAN	Sphingosine kinase 2 Sphingosine kinase 2	SPHK2	49	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	49	P → S in CAB66636 (PubMed:11230166).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_060112	652	R → Q. Corresponds to variant dbSNP:rs11881285Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_006217	1 – 36	Missing in isoform 2 and isoform 3. 4 PublicationsAdd BLAST	36
Alternative sequenceⁱVSP_047721	1 – 12	MNGHL…EEQQD → MIGCLHARVSGPLWDAGLCP ASSRSAHTCLSLSVSDAPVS PATAPHCLLLSTAPAPPCPC HGVLNSHPFSPPFP in isoform 5. 1 PublicationAdd BLAST	12
Alternative sequenceⁱVSP_046910	13 – 71	Missing in isoform 4. 1 PublicationAdd BLAST	59
Alternative sequenceⁱVSP_006218	292 – 390	FEPAL…ASPTP → PREDSDSSTSSSACPLWTTA RSCPRAAASMPGSCPLLPQQ LALGFSRFIQDRVNGGGGRI GSLTCRGHTQRTLPAPAREG GGSLFLKNINVFICKKKKK in isoform 3. 1 PublicationAdd BLAST	99
Alternative sequenceⁱVSP_047722	640 – 654	GTLLT…PGREP → ARGRTQTPALPAAPALYGRQ PGAAHGLQPVCQGAALFFHN SWLWGSQDLFRIVLTEAVGG in isoform 5. 1 PublicationAdd BLAST	15

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12727.1 [Q9NRA0-1] CCDS59404.1 [Q9NRA0-4] CCDS59405.1 [Q9NRA0-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_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_006723355.1, XM_006723292.1 [Q9NRA0-2] XP_011525435.1, XM_011527133.1 [Q9NRA0-1] XP_011525436.1, XM_011527134.1 [Q9NRA0-2]

Genome annotation databases

Ensemblⁱ	ENST00000245222.9; ENSP00000245222.3; ENSG00000063176.16 ENST00000598088.5; ENSP00000469158.1; ENSG00000063176.16 ENST00000599748.5; ENSP00000471205.1; ENSG00000063176.16 [Q9NRA0-2] ENST00000600537.5; ENSP00000470092.1; ENSG00000063176.16 [Q9NRA0-4]
GeneIDⁱ	56848
KEGGⁱ	hsa:56848
MANE-Selectⁱ	ENST00000245222.9; ENSP00000245222.3; NM_020126.5; NP_064511.2
UCSC genome browser More...UCSCⁱ	uc002pjr.4, human [Q9NRA0-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9NRA0	Sphingosine kinase 2, isoform CRA_c		HUMAN		654	UniRef100_Q9NRA0
Q9NRA0-3	Sphingosine kinase 2		HUMAN		349	UniRef100_A0A075B7A1
Q9NRA0-5	Sphingosine kinase 2		HUMAN		663	UniRef100_M0R344
SPHK2 isoform 8 (Fragment)		PONAB		133
Sphingosine kinase 2 (Fragment)		HUMAN		133
Sphingosine kinase 2 (Fragment)		HUMAN		72
SPHK2 isoform 9 (Fragment)		PONAB		72
+2

Protein	Similar proteins		Species	Score	Length	Source
Q9NRA0	Sphingosine kinase 2, isoform CRA_c		HUMAN		654	UniRef90_Q9NRA0
Sphingosine kinase 2		PONAB		678
Sphingosine kinase 2		MACMU		669
DAGKc domain-containing protein		RHIRO		665
Sphingosine kinase 2		GORGO		663
+123
Q9NRA0-3	Sphingosine kinase 2		HUMAN		349	UniRef90_A0A075B7A1
Q9NRA0-4	sphingosine kinase 2 isoform X1		SAPAP		694	UniRef90_Q9NRA0-4
Sphingosine kinase 2		AOTNA		657
Sphingosine kinase 2		SAIBB		656
sphingosine kinase 2 isoform X2		CARSF		595
SPHK2 isoform 4		PANTR		595
+6

Protein	Similar proteins		Species	Score	Length	Source
Q9NRA0	Sphingosine kinase 2		MOUSE		617	UniRef50_Q9NRA0
Sphingosine kinase 2, isoform CRA_c		HUMAN		654
Sphingosine kinase 2		PONAB		678
Sphingosine kinase 2		MACMU		669
DAGKc domain-containing protein		RHIRO		665
+241

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS12727.1 [Q9NRA0-1] CCDS59404.1 [Q9NRA0-4] CCDS59405.1 [Q9NRA0-2]
RefSeqⁱ	NP_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_006723355.1, XM_006723292.1 [Q9NRA0-2] XP_011525435.1, XM_011527133.1 [Q9NRA0-1] XP_011525436.1, XM_011527134.1 [Q9NRA0-2]

3D structure databases

AlphaFoldDBⁱ	Q9NRA0
SMRⁱ	Q9NRA0
ModBaseⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	121208, 19 interactors
IntActⁱ	Q9NRA0, 7 interactors
STRINGⁱ	9606.ENSP00000245222

Chemistry databases

BindingDBⁱ	Q9NRA0
ChEMBLⁱ	CHEMBL3023
DrugBankⁱ	DB12764, Opaganib
GuidetoPHARMACOLOGYⁱ	2205
SwissLipidsⁱ	SLP:000000112

PTM databases

iPTMnetⁱ	Q9NRA0
PhosphoSitePlusⁱ	Q9NRA0

Genetic variation databases

BioMutaⁱ	SPHK2
DMDMⁱ	22001996

Proteomic databases

EPDⁱ	Q9NRA0
jPOSTⁱ	Q9NRA0
MassIVEⁱ	Q9NRA0
MaxQBⁱ	Q9NRA0
PaxDbⁱ	Q9NRA0
PeptideAtlasⁱ	Q9NRA0
PRIDEⁱ	Q9NRA0
ProteomicsDBⁱ	82315 [Q9NRA0-1] 82316 [Q9NRA0-2] 82317 [Q9NRA0-3] 86

Protocols and materials databases

Antibodypediaⁱ	31745, 453 antibodies from 37 providers
The DNASU plasmid repository More...DNASUⁱ	56848

Genome annotation databases

Ensemblⁱ	ENST00000245222.9; ENSP00000245222.3; ENSG00000063176.16 ENST00000598088.5; ENSP00000469158.1; ENSG00000063176.16 ENST00000599748.5; ENSP00000471205.1; ENSG00000063176.16 [Q9NRA0-2] ENST00000600537.5; ENSP00000470092.1; ENSG00000063176.16 [Q9NRA0-4]
GeneIDⁱ	56848
KEGGⁱ	hsa:56848
MANE-Selectⁱ	ENST00000245222.9; ENSP00000245222.3; NM_020126.5; NP_064511.2
UCSCⁱ	uc002pjr.4, human [Q9NRA0-1]

Organism-specific databases

CTDⁱ	56848
DisGeNETⁱ	56848
GeneCardsⁱ	SPHK2
HGNCⁱ	HGNC:18859, SPHK2
HPAⁱ	ENSG00000063176, Low tissue specificity
MIMⁱ	607092, gene
neXtProtⁱ	NX_Q9NRA0
OpenTargetsⁱ	ENSG00000063176
PharmGKBⁱ	PA38719
VEuPathDBⁱ	HostDB:ENSG00000063176
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG1116, Eukaryota
GeneTreeⁱ	ENSGT00940000161197
HOGENOMⁱ	CLU_013399_1_1_1
InParanoidⁱ	Q9NRA0
OMAⁱ	EREDGMM
OrthoDBⁱ	681139at2759
PhylomeDBⁱ	Q9NRA0
TreeFamⁱ	TF354296

Enzyme and pathway databases

BRENDAⁱ	2.7.1.91, 2681
PathwayCommonsⁱ	Q9NRA0
Reactomeⁱ	R-HSA-1660661, Sphingolipid de novo biosynthesis
SignaLinkⁱ	Q9NRA0
SIGNORⁱ	Q9NRA0

Miscellaneous databases

BioGRID-ORCSⁱ	56848, 26 hits in 1083 CRISPR screens
ChiTaRSⁱ	SPHK2, human
GeneWikiⁱ	SPHK2
GenomeRNAiⁱ	56848
Pharosⁱ	Q9NRA0, Tchem
Protein Ontology More...PROⁱ	PR:Q9NRA0
RNActⁱ	Q9NRA0, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000063176, Expressed in substantia nigra and 173 other tissues
ExpressionAtlasⁱ	Q9NRA0, baseline and differential
Genevisibleⁱ	Q9NRA0, HS

Family and domain databases

Gene3Dⁱ	3.40.50.10330, 1 hit
InterProⁱ	View protein in InterPro IPR017438, ATP-NAD_kinase_N IPR001206, Diacylglycerol_kinase_cat_dom IPR016064, NAD/diacylglycerol_kinase_sf IPR045540, YegS/DAGK_C
Pfamⁱ	View protein in Pfam PF00781, DAGK_cat, 1 hit PF19279, YegS_C, 1 hit
SMARTⁱ	View protein in SMART SM00046, DAGKc, 1 hit
SUPFAMⁱ	SSF111331, SSF111331, 1 hit
PROSITEⁱ	View protein in PROSITE PS50146, DAGK, 1 hit
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	SPHK2_HUMAN
Accessionⁱ	Q9NRA0Primary (citable) accession number: Q9NRA0 Secondary accession number(s): A0T4C8 , B4DU87, Q9BRN1, Q9H0Q2, Q9NWU7
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 24, 2001
	Last sequence update:	July 26, 2002
	Last modified:	May 25, 2022
	This is version 180 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

Reference proteome

Documents

Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - Q9NRA0 (SPHK2_HUMAN)

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Sphingosine kinase 2

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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Enzyme and pathway databases

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<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Q9NRA0

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<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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Phylogenomic databases

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Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

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Chemistry databases

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Functionⁱ

Catalytic activityⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ