SPHK2

Protein identityUniProt · HPA

UniProt accession

Q9NRA0

Gene

SPHK2

Ensembl

ENSG00000063176

Chromosome

19

Canonical length

654 aa

Protein class

Disease related genes, Enzymes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

654 residues, UniProt reviewed canonical sequence.

>Q9NRA0|SPHK2
     1  MNGHLEAEEQ QDQRPDQELT GSWGHGPRST LVRAKAMAPP PPPLAASTPL LHGEFGSYPA
    61  RGPRFALTLT SQALHIQRLR PKPEARPRGG LVPLAEVSGC CTLRSRSPSD SAAYFCIYTY
   121  PRGRRGARRR ATRTFRADGA ATYEENRAEA QRWATALTCL LRGLPLPGDG EITPDLLPRP
   181  PRLLLLVNPF GGRGLAWQWC KNHVLPMISE AGLSFNLIQT ERQNHARELV QGLSLSEWDG
   241  IVTVSGDGLL HEVLNGLLDR PDWEEAVKMP VGILPCGSGN ALAGAVNQHG GFEPALGLDL
   301  LLNCSLLLCR GGGHPLDLLS VTLASGSRCF SFLSVAWGFV SDVDIQSERF RALGSARFTL
   361  GTVLGLATLH TYRGRLSYLP ATVEPASPTP AHSLPRAKSE LTLTPDPAPP MAHSPLHRSV
   421  SDLPLPLPQP ALASPGSPEP LPILSLNGGG PELAGDWGGA GDAPLSPDPL LSSPPGSPKA
   481  ALHSPVSEGA PVIPPSSGLP LPTPDARVGA STCGPPDHLL PPLGTPLPPD WVTLEGDFVL
   541  MLAISPSHLG ADLVAAPHAR FDDGLVHLCW VRSGISRAAL LRLFLAMERG SHFSLGCPQL
   601  GYAAARAFRL EPLTPRGVLT VDGEQVEYGP LQAQMHPGIG TLLTGPPGCP GREP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SPHK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

38 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.02

gnomAD pLI

0

gnomAD missense Z

1.32

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood vessel development
• brain development
• cell population proliferation
• cellular response to phorbol 13-acetate 12-myristate
• female pregnancy
• intracellular signal transduction
• negative regulation of cell growth
• positive regulation of apoptotic process
• positive regulation of cell population proliferation
• positive regulation of ceramide biosynthetic process
• positive regulation of cytokine production involved in immune response
• positive regulation of interleukin-13 production
• positive regulation of interleukin-6 production
• positive regulation of mast cell degranulation
• positive regulation of tumor necrosis factor production
• regulation of canonical NF-kappaB signal transduction
• regulation of cytochrome-c oxidase activity
• regulation of reactive oxygen species biosynthetic process
• sphingolipid biosynthetic process
• sphingosine biosynthetic process
• sphingosine metabolic process
• transcription initiation-coupled chromatin remodeling
• positive regulation of mast cell activation involved in immune response
• regulation of ATP biosynthetic process
• sphinganine-1-phosphate biosynthetic process

Molecular functions

• ATP binding
• histone binding
• lipid kinase activity
• small GTPase binding
• sphingosine kinase activity
• sphingosine-1-phosphate receptor activity

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum
• lysosomal membrane
• membrane
• mitochondrial inner membrane
• mitochondrion
• nucleoplasm
• nucleosome
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Diacylglycerol kinase, catalytic domain
• NAD kinase/diacylglycerol kinase-like domain superfamily
• Inorganic polyphosphate/ATP-NAD kinase, N-terminal
• Lipid Phosphate Formation and Regulation
• Diacylglycerol kinase catalytic domain
• YegS/DAGK, C-terminal domain
• YegS C-terminal NAD kinase beta sandwich-like domain

KeywordsUniProt

• ATP-binding
• Cytoplasm
• Endoplasmic reticulum
• Kinase
• Lipid metabolism
• Lysosome
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of SPHK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EEF1A1
• HDAC1
• HDAC2
• MBD2
• PHB2
• SIN3A