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    SPHK2 sphingosine kinase 2 [ Homo sapiens (human) ]

    Gene ID: 56848, updated on 14-Nov-2024

    Summary

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    Official Symbol
    SPHK2provided by HGNC
    Official Full Name
    sphingosine kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:18859
    See related
    Ensembl:ENSG00000063176 MIM:607092; AllianceGenome:HGNC:18859
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SK 2; SK-2; SPK 2; SPK-2
    Summary
    This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in kidney (RPKM 6.4), duodenum (RPKM 5.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPHK2 in Genome Data Viewer
    Location:
    19q13.33
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (48619506..48630405)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (51613990..51624887)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (49122763..49133662)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 83 member E Neighboring gene sperm acrosome associated 4 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:49117268-49117444 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:49117749-49118580 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:49118581-49119412 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:49119413-49120243 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:49121076-49121906 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14902 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14903 Neighboring gene ribosomal protein L18 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10889 Neighboring gene Sharpr-MPRA regulatory region 2382 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:49130943-49131443 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10890 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10891 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10892 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10893 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10894 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10895 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14904 Neighboring gene D-box binding PAR bZIP transcription factor Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr19:49147372-49148073 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:49148074-49148774 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:49148775-49149475 Neighboring gene secretory blood group 1, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10896 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10897 Neighboring gene carbonic anhydrase 11 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:49166921-49167422 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:49167423-49167922 Neighboring gene netrin 5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Down-regulation of sphingosine kinase 2 (SphK2) increases the effects of all-trans-retinoic acid (ATRA) on colon cancer cells. Chu JH, et al. Biomed Pharmacother, 2014 Oct. PMID 25455157
    2. Metabolic Adaptation of Airway Smooth Muscle Cells to an SPHK2 Substrate Precedes Cytostasis. Blais-Lecours P, et al. Am J Respir Cell Mol Biol, 2020 Jan. PMID 31247144, Free PMC Article
    3. Decreased S1P and SPHK2 are involved in pancreatic acinar cell injury. Xiao J, et al. Biomark Med, 2019 Jun. PMID 31157539
    4. Sphingosine kinase 2: a controversial role in arthritis. Xu T, et al. Rheumatol Int, 2014 Jul. PMID 23881266
    5. In vitro and in vivo roles of sphingosine kinase 2 during dengue virus infection. Al-Shujairi WH, et al. J Gen Virol, 2019 Apr. PMID 30869582

    See all (114) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.
      Title: Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.
    2. YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis.
      Title: YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis.
    3. The accumulation of sphingosine kinase 2 disrupts the DNA damage response and promotes resistance to genotoxic agents.
      Title: The accumulation of sphingosine kinase 2 disrupts the DNA damage response and promotes resistance to genotoxic agents.
    4. Accumulation of sphingosine kinase 2 protein induces malignant transformation in oral keratinocytes associated with stemness, autophagy, senescence, and proliferation.
      Title: Accumulation of sphingosine kinase 2 protein induces malignant transformation in oral keratinocytes associated with stemness, autophagy, senescence, and proliferation.
    5. Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma.
      Title: Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma.
    6. Sphingosine kinase 2 regulates insulin receptor trafficking in hepatocytes.
      Title: Sphingosine kinase 2 regulates insulin receptor trafficking in hepatocytes.
    7. miR-153-3p Attenuates the Development of Gastric Cancer by Suppressing SphK2.
      Title: miR-153-3p Attenuates the Development of Gastric Cancer by Suppressing SphK2.
    8. Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.
      Title: Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.
    9. Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.
      Title: Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.
    10. Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition.
      Title: Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition.
    Submit: New GeneRIF Correction See all GeneRIFs (84)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    EBI GWAS Catalog

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables D-erythro-sphingosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables D-erythro-sphingosine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables lipid kinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables sphingosine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sphingosine-1-phosphate receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in blood vessel development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in brain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to phorbol 13-acetate 12-myristate IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in female pregnancy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of cell growth ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of ceramide biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cytokine production involved in immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of interleukin-13 production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of interleukin-6 production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of mast cell activation involved in immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of mast cell degranulation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of tumor necrosis factor production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of ATP biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of canonical NF-kappaB signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of cytochrome-c oxidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of reactive oxygen species biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sphinganine-1-phosphate biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sphinganine-1-phosphate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sphingolipid biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in sphingosine biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sphingosine biosynthetic process IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in sphingosine biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in sphingosine metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sphingosine-1-phosphate receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in transcription initiation-coupled chromatin remodeling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in intracellular membrane-bounded organelle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosomal membrane HDA PubMed 
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    part_of nucleosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sphingosine kinase 2
    NP_001191087.1
    NP_001191088.1
    NP_001191089.1
    NP_001230805.1
    NP_064511.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029867.1 RefSeqGene

      Range
      5216..16115
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001204158.3 → NP_001191087.1  sphingosine kinase 2 isoform b

      See identical proteins and their annotated locations for NP_001191087.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a.
      Source sequence(s)
      AK122735, AK300541, DB367710
      Consensus CDS
      CCDS59404.1
      UniProtKB/TrEMBL
      B3KV83
      Related
      ENSP00000470092.1, ENST00000600537.5
      Conserved Domains (1) summary
      pfam00781
      Location:128 → 262
      DAGK_cat; Diacylglycerol kinase catalytic domain

    2. NM_001204159.3 → NP_001191088.1  sphingosine kinase 2 isoform a

      See identical proteins and their annotated locations for NP_001191088.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 both encode the same isoform (a).
      Source sequence(s)
      AC022154, AF245447, AL136701, DB053266
      Consensus CDS
      CCDS12727.1
      UniProtKB/Swiss-Prot
      A0T4C8, B4DU87, Q9BRN1, Q9H0Q2, Q9NRA0, Q9NWU7
      UniProtKB/TrEMBL
      B3KV83
      Related
      ENSP00000469158.1, ENST00000598088.5
      Conserved Domains (1) summary
      pfam00781
      Location:187 → 321
      DAGK_cat; Diacylglycerol kinase catalytic domain

    3. NM_001204160.3 → NP_001191089.1  sphingosine kinase 2 isoform c

      See identical proteins and their annotated locations for NP_001191089.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (c) has a shorter N-terminus, compared to isoform a.
      Source sequence(s)
      BC010671
      Consensus CDS
      CCDS59405.1
      UniProtKB/TrEMBL
      M0R344
      Related
      ENSP00000471205.1, ENST00000599748.5
      Conserved Domains (1) summary
      pfam00781
      Location:151 → 285
      DAGK_cat; Diacylglycerol kinase catalytic domain

    4. NM_001243876.2 → NP_001230805.1  sphingosine kinase 2 isoform d

      See identical proteins and their annotated locations for NP_001230805.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an exon in the coding region and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (d) has a shorter N-terminus, compared to isoform a.
      Source sequence(s)
      AK122735, DA926908, DB367710
      Consensus CDS
      CCDS74414.1
      UniProtKB/TrEMBL
      E9PCV4
      Related
      ENSP00000341091.4, ENST00000340932.7
      Conserved Domains (2) summary
      PLN02958
      Location:1 → 175
      PLN02958; diacylglycerol kinase/D-erythro-sphingosine kinase
      PHA03247
      Location:149 → 310
      PHA03247; large tegument protein UL36; Provisional

    5. NM_020126.5 → NP_064511.2  sphingosine kinase 2 isoform a

      See identical proteins and their annotated locations for NP_064511.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 3 both encode the same isoform (a).
      Source sequence(s)
      BC006161
      Consensus CDS
      CCDS12727.1
      UniProtKB/Swiss-Prot
      A0T4C8, B4DU87, Q9BRN1, Q9H0Q2, Q9NRA0, Q9NWU7
      UniProtKB/TrEMBL
      B3KV83
      Related
      ENSP00000245222.3, ENST00000245222.9
      Conserved Domains (1) summary
      pfam00781
      Location:187 → 321
      DAGK_cat; Diacylglycerol kinase catalytic domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      48619506..48630405
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      51613990..51624887
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NRA0.2 GenPept UniProtKB/Swiss-Prot:Q9NRA0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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