UniProtKB - Q9NRA0 (SPHK2_HUMAN)
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Protein
Sphingosine kinase 2
Gene
SPHK2
Organism
Homo sapiens (Human)
Status
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.1 Publication
Catalytic activityi
ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate.1 Publication
Cofactori
Mg2+By similarity
Enzyme regulationi
Inhibited by sulfatide.1 Publication
Kineticsi
- KM=3.4 µM for sphingosine1 Publication
pH dependencei
Optimum pH is 7.5.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | 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 | Graphical view | 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
- ATP binding Source: UniProtKB-KW
- D-erythro-sphingosine kinase activity Source: Reactome
- NAD+ kinase activity Source: InterPro
- Ras GTPase binding Source: UniProtKB
- sphinganine kinase activity Source: Reactome
- sphingosine-1-phosphate receptor activity Source: UniProtKB
GO - Biological processi
- blood vessel development Source: Ensembl
- brain development Source: Ensembl
- cell proliferation Source: UniProtKB
- female pregnancy Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- positive regulation of cell proliferation Source: Ensembl
- sphinganine-1-phosphate biosynthetic process Source: UniProtKB
- sphingolipid biosynthetic process Source: Reactome
- sphingosine biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.1.91. 2681. |
Reactomei | R-HSA-1660661. Sphingolipid de novo biosynthesis. |
SIGNORi | Q9NRA0. |
Chemistry databases
SwissLipidsi | SLP:000000112. |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:SPHK2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000063176.15. |
HGNCi | HGNC:18859. SPHK2. |
MIMi | 607092. gene. |
neXtProti | NX_Q9NRA0. |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 56848. |
OpenTargetsi | ENSG00000063176. |
PharmGKBi | PA38719. |
Chemistry databases
ChEMBLi | CHEMBL3023. |
GuidetoPHARMACOLOGYi | 2205. |
Polymorphism and mutation 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 | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 387 | PhosphoserineCombined sources | 1 | |
Modified residuei | 393 | PhosphoserineBy similarity | 1 | |
Modified residuei | 399 | PhosphoserineCombined sources | 1 | |
Modified residuei | 477 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9NRA0. |
MaxQBi | Q9NRA0. |
PaxDbi | Q9NRA0. |
PeptideAtlasi | Q9NRA0. |
PRIDEi | Q9NRA0. |
PTM databases
iPTMneti | Q9NRA0. |
PhosphoSitePlusi | Q9NRA0. |
Expressioni
Gene expression databases
Bgeei | ENSG00000063176. |
ExpressionAtlasi | Q9NRA0. baseline and differential. |
Genevisiblei | Q9NRA0. HS. |
Organism-specific databases
HPAi | HPA065508. |
Interactioni
GO - Molecular functioni
- Ras GTPase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 121208. 3 interactors. |
IntActi | Q9NRA0. 5 interactors. |
STRINGi | 9606.ENSP00000245222. |
Chemistry databases
BindingDBi | Q9NRA0. |
Structurei
3D structure databases
ProteinModelPortali | Q9NRA0. |
SMRi | Q9NRA0. |
ModBasei | Search... |
MobiDBi | 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 | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 175 | Required for binding to sulfatide and phosphoinositides and for membrane localizationAdd BLAST | 175 | |
Regioni | 245 – 248 | Substrate bindingBy similarity | 4 |
Phylogenomic databases
eggNOGi | KOG1116. Eukaryota. COG1597. LUCA. |
GeneTreei | ENSGT00690000101761. |
HOGENOMi | HOG000111460. |
HOVERGENi | HBG054796. |
InParanoidi | Q9NRA0. |
KOi | K04718. |
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. |
Pfami | View protein in Pfam PF00781. DAGK_cat. 1 hit. |
SMARTi | View protein in SMART SM00046. DAGKc. 1 hit. |
SUPFAMi | SSF111331. SSF111331. 2 hits. |
PROSITEi | View protein in PROSITE PS50146. DAGK. 1 hit. |
s (5)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basket
Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9NRA0-1) [UniParc]FASTAAdd to basket
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.
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
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 | Graphical view | 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. |
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] |
UniGenei | Hs.528006. |
Genome annotation databases
Ensembli | ENST00000245222; ENSP00000245222; ENSG00000063176. [Q9NRA0-1] ENST00000598088; ENSP00000469158; ENSG00000063176. [Q9NRA0-1] ENST00000599748; ENSP00000471205; ENSG00000063176. [Q9NRA0-2] ENST00000600537; ENSP00000470092; ENSG00000063176. [Q9NRA0-4] |
GeneIDi | 56848. |
KEGGi | hsa:56848. |
UCSCi | uc002pjr.4. human. [Q9NRA0-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | SPHK2_HUMAN | |
Accessioni | Q9NRA0Primary (citable) accession number: Q9NRA0 Secondary accession number(s): A0T4C8 Q9NWU7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 24, 2001 |
Last sequence update: | July 26, 2002 | |
Last modified: | February 28, 2018 | |
This is version 156 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. |