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UniProtKB - Q9NRA0 (SPHK2_HUMAN)

Entry version 165 (03 Jul 2019)
Sequence version 2 (26 Jul 2002)
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Protein

Sphingosine kinase 2

Gene

SPHK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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

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. Upregulates 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

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei247Proton donor/acceptorBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei252ATPPROSITE-ProRule annotation1
Binding sitei344SubstrateBy similarity1
Binding sitei351ATPPROSITE-ProRule annotation1
Binding sitei357ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi188 – 190ATPPROSITE-ProRule annotation3
Nucleotide bindingi220 – 224ATPPROSITE-ProRule annotation5
Nucleotide bindingi277 – 279ATPPROSITE-ProRule annotation3
Nucleotide bindingi622 – 624ATPPROSITE-ProRule annotation3

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.1.91 2681

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1660661 Sphingolipid de novo biosynthesis

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q9NRA0

Chemistry databases

SwissLipids knowledge resource for lipid biology

More...SwissLipidsi		SLP:000000112

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Sphingosine kinase 2Curated (EC:2.7.1.913 Publications)
Short name:
SK 2
Short name:
SPK 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SPHK2Imported
Synonyms:SK2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 19

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:18859 SPHK2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		607092 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9NRA0

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

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

<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

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi138D → A: Abolishes cleavage and secretion in apoptotic cells. No effect on kinase activity. 1 Publication1
Mutagenesisi212G → E: Decreases SPP production in nucleus. Abolishes increase of histone acetylation. No effect on association with histone 3. 1 Publication1
Mutagenesisi220T → A: Loss of location to cell membrane. Not secreted. No effect on kinase acitivity. 1 Publication1
Mutagenesisi387S → A: Strongly reduces phosphorylation levels. 1 Publication1
Mutagenesisi419 – 421SVS → AVA: Abolishes nuclear export in response to PMA treatment. 1 Publication3
Mutagenesisi423 – 425LPL → APA: Abolishes nuclear export. 1 Publication3
Mutagenesisi437S → A: Reduces phosphorylation levels. 1 Publication1
Mutagenesisi466S → A: Reduces phosphorylation levels. 1 Publication1
Mutagenesisi477S → A: Reduces phosphorylation levels. 1 Publication1
Mutagenesisi552D → A: No effect on cleavage and secretion in apoptotic cells. No effect on kinase activity. 1 Publication1
Mutagenesisi614T → A: Abolishes phosphorylation. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		56848

Open Targets

More...OpenTargetsi		ENSG00000063176

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA38719

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3023

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2205

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SPHK2

Domain mapping of disease mutations (DMDM)

More...DMDMi		22001996

<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

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001813581 – 654Sphingosine kinase 2Add BLAST654

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei387Phosphoserine; by MAPKCombined sources1 Publication1
Modified residuei393PhosphoserineBy similarity1
Modified residuei399PhosphoserineCombined sources1
Modified residuei419Phosphoserine; by PKD1 Publication1
Modified residuei421Phosphoserine; by PKD1 Publication1
Modified residuei477PhosphoserineCombined sources1
Modified residuei614Phosphothreonine; by MAPK1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...EPDi		Q9NRA0

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9NRA0

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9NRA0

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9NRA0

PeptideAtlas

More...PeptideAtlasi		Q9NRA0

PRoteomics IDEntifications database

More...PRIDEi		Q9NRA0

ProteomicsDB human proteome resource

More...ProteomicsDBi		82315
82316 [Q9NRA0-2]
82317 [Q9NRA0-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9NRA0

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9NRA0

<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

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000063176 Expressed in 160 organ(s), highest expression level in substantia nigra

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9NRA0 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9NRA0 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		HPA065508

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		121208, 9 interactors

Protein interaction database and analysis system

More...IntActi		Q9NRA0, 5 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000245222

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q9NRA0

<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

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9NRA0

Database of comparative protein structure models

More...ModBasei		Search...

<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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini178 – 325DAGKcPROSITE-ProRule annotationAdd BLAST148

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 175Required for binding to sulfatide and phosphoinositides and for membrane localizationAdd BLAST175
Regioni245 – 248Substrate bindingBy similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi122 – 130NLSBy similarity9
Motifi416 – 425NES1 Publication10

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1116 Eukaryota
COG1597 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000161197

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000111460

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9NRA0

KEGG Orthology (KO)

More...KOi		K04718

Database of Orthologous Groups

More...OrthoDBi		866496at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9NRA0

TreeFam database of animal gene trees

More...TreeFami		TF354296

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.50.10330, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR017438 ATP-NAD_kinase_N
IPR001206 Diacylglycerol_kinase_cat_dom
IPR016064 NAD/diacylglycerol_kinase_sf

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00781 DAGK_cat, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00046 DAGKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF111331 SSF111331, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50146 DAGK, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (5+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 5 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd 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 allAlign All

Isoform 1 (identifier: Q9NRA0-1) [UniParc]FASTAAdd to basket
Also known as: SK2B, SK2-L1 Publication

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>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.

« Hide
        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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iF73FFCEC930DA50F
GO
Isoform 2 (identifier: Q9NRA0-2) [UniParc]FASTAAdd to basket
Also known as: SK2A, SK2-S1 Publication

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

Show »
Length:618
Mass (Da):65,205
Checksum:i1A5B06BCB6F93F1F
GO
Isoform 3 (identifier: Q9NRA0-3) [UniParc]FASTAAdd to basket

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

Show »
Length:618
Mass (Da):65,170
Checksum:iD934F61C0A69EDAE
GO
Isoform 4 (identifier: Q9NRA0-4) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:595
Mass (Da):62,986
Checksum:iC24AC949EEEA059B
GO
Isoform 5 (identifier: Q9NRA0-5) [UniParc]FASTAAdd to basket

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

Show »
Length:761
Mass (Da):80,205
Checksum:iA52BF3441102A3D3
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R344M0R344_HUMAN
Sphingosine kinase 2
SPHK2
663Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
M0R0E9M0R0E9_HUMAN
Sphingosine kinase 2
SPHK2
255Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PCV4E9PCV4_HUMAN
Sphingosine kinase 2
SPHK2 hCG_15274
448Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A075B7A1A0A075B7A1_HUMAN
Sphingosine kinase 2
SPHK2
349Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
M0QXX5M0QXX5_HUMAN
Sphingosine kinase 2
SPHK2
133Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
M0QZP3M0QZP3_HUMAN
Sphingosine kinase 2
SPHK2
72Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E7ET12E7ET12_HUMAN
Sphingosine kinase 2
SPHK2
49Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti49P → S in CAB66636 (PubMed:11230166).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_060112652R → Q. Corresponds to variant dbSNP:rs11881285Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0062171 – 36Missing in isoform 2 and isoform 3. 4 PublicationsAdd BLAST36
Alternative sequenceiVSP_0477211 – 12MNGHL…EEQQD → MIGCLHARVSGPLWDAGLCP ASSRSAHTCLSLSVSDAPVS PATAPHCLLLSTAPAPPCPC HGVLNSHPFSPPFP in isoform 5. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_04691013 – 71Missing in isoform 4. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_006218292 – 390FEPAL…ASPTP → PREDSDSSTSSSACPLWTTA RSCPRAAASMPGSCPLLPQQ LALGFSRFIQDRVNGGGGRI GSLTCRGHTQRTLPAPAREG GGSLFLKNINVFICKKKKK in isoform 3. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_047722640 – 654GTLLT…PGREP → ARGRTQTPALPAAPALYGRQ PGAAHGLQPVCQGAALFFHN SWLWGSQDLFRIVLTEAVGG in isoform 5. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000245222; ENSP00000245222; ENSG00000063176 [Q9NRA0-1]
ENST00000598088; ENSP00000469158; ENSG00000063176 [Q9NRA0-1]
ENST00000599748; ENSP00000471205; ENSG00000063176 [Q9NRA0-2]
ENST00000600537; ENSP00000470092; ENSG00000063176 [Q9NRA0-4]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		56848

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:56848

UCSC genome browser

More...UCSCi		uc002pjr.4 human [Q9NRA0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<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

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
CCDSiCCDS12727.1 [Q9NRA0-1]
CCDS59404.1 [Q9NRA0-4]
CCDS59405.1 [Q9NRA0-2]
RefSeqiNP_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

SMRiQ9NRA0
ModBaseiSearch...

Protein-protein interaction databases

BioGridi121208, 9 interactors
IntActiQ9NRA0, 5 interactors
STRINGi9606.ENSP00000245222

Chemistry databases

BindingDBiQ9NRA0
ChEMBLiCHEMBL3023
GuidetoPHARMACOLOGYi2205
SwissLipidsiSLP:000000112

PTM databases

iPTMnetiQ9NRA0
PhosphoSitePlusiQ9NRA0

Polymorphism and mutation databases

BioMutaiSPHK2
DMDMi22001996

Proteomic databases

EPDiQ9NRA0
jPOSTiQ9NRA0
MaxQBiQ9NRA0
PaxDbiQ9NRA0
PeptideAtlasiQ9NRA0
PRIDEiQ9NRA0
ProteomicsDBi82315
82316 [Q9NRA0-2]
82317 [Q9NRA0-3]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		56848
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245222; ENSP00000245222; ENSG00000063176 [Q9NRA0-1]
ENST00000598088; ENSP00000469158; ENSG00000063176 [Q9NRA0-1]
ENST00000599748; ENSP00000471205; ENSG00000063176 [Q9NRA0-2]
ENST00000600537; ENSP00000470092; ENSG00000063176 [Q9NRA0-4]
GeneIDi56848
KEGGihsa:56848
UCSCiuc002pjr.4 human [Q9NRA0-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		56848
DisGeNETi56848

GeneCards: human genes, protein and diseases

More...GeneCardsi		SPHK2
HGNCiHGNC:18859 SPHK2
HPAiHPA065508
MIMi607092 gene
neXtProtiNX_Q9NRA0
OpenTargetsiENSG00000063176
PharmGKBiPA38719

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1116 Eukaryota
COG1597 LUCA
GeneTreeiENSGT00940000161197
HOGENOMiHOG000111460
InParanoidiQ9NRA0
KOiK04718
OrthoDBi866496at2759
PhylomeDBiQ9NRA0
TreeFamiTF354296

Enzyme and pathway databases

BRENDAi2.7.1.91 2681
ReactomeiR-HSA-1660661 Sphingolipid de novo biosynthesis
SIGNORiQ9NRA0

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		SPHK2 human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		SPHK2

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		56848

Protein Ontology

More...PROi		PR:Q9NRA0

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000063176 Expressed in 160 organ(s), highest expression level in substantia nigra
ExpressionAtlasiQ9NRA0 baseline and differential
GenevisibleiQ9NRA0 HS

Family and domain databases

Gene3Di3.40.50.10330, 1 hit
InterProiView protein in InterPro
IPR017438 ATP-NAD_kinase_N
IPR001206 Diacylglycerol_kinase_cat_dom
IPR016064 NAD/diacylglycerol_kinase_sf
PfamiView protein in Pfam
PF00781 DAGK_cat, 1 hit
SMARTiView protein in SMART
SM00046 DAGKc, 1 hit
SUPFAMiSSF111331 SSF111331, 1 hit
PROSITEiView protein in PROSITE
PS50146 DAGK, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSPHK2_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9NRA0
Secondary accession number(s): A0T4C8
, B4DU87, Q9BRN1, Q9H0Q2, Q9NWU7
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 24, 2001
Last sequence update: July 26, 2002
Last modified: July 3, 2019
This is version 165 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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