Sphingolipid pathway (Homo sapiens)

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1, 322(DH)Cer synthasesDihydroceramideDihydrosphingosineCDaseDHSMCerS2DHSTACER1SMS2PPAP2AASAH1C16:0-alSGPP2CerS5ASAH1SoP lyase1CERKSPT2SPHK1ASAH2SGPP2CeramidesDHCer1PSphinganineB4GALT6CerS1CERTCerS4ACER1PPAP2A3-ketodihydroshpingosinePhosphataseSa 1-phosphateSphingosineDHLacCerPalmityl-CoACerS6SPT1SPHK2S1P lyaseSerineASAH2PP1SPHK1DHGalCerEthanolamine phosphateSPHK2GAL3ST1C16:1-alDHGlcCer3-ketosphinganineSPT3KDSRFVT1CerS3SMS1Sphingosine 1-phosphateFumonisins B1Cer1PCERTGalCerSphingomyelinSMS2GlcCerSMS1LactosylceramideGAL3ST1CERKSulfatideB4GALT6PP2A(DH)Cer synthasesCerS1CerS6CerS5CerS4CerS3CerS2CERTGBAGlucosylceramidaseGBA2GalCer synthaseGlcCer synthaseGalCer synthaseGlcCer synthaseDEGS2DEGS1Dihydroceramide desaturaseSGMS2SGMS1SGPL1CoA(16:0)CoA(18:0)CoA(20:0)CoA(22:0)CoA(24:0)CoA(24:1)CoA(26:0)CoA(26:1)


Description

The sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form 3-ketosphinganine (3-ketoSa) by serine palmitoyltransferase, which is reduced to sphinganine (Sa), acylated to dihydroceramides, DHCer, by (DH)Cer synthases, and incorporated into more complex DH-sphingolipids (the 1-phosphate, DHCerP, sphingomyelins, DHSM, glucosylceramides, DHGlcCer, galactosylceramides, DHGalCer, lactosylceramides, DHLacCer, and sulfatides, or desaturated to Cer followed by headgroup addition. Also included are a number of the catabolic genes, e.g., sphingomyelinases, SMases, ceramidases, ASAH, sphingosine kinases, for the formation of sphinganine 1-phosphate (Sa1P) and sphingosine 1-phosphate (So1P), and phosphatases for the reverse reaction and the lyase that cleaves sphingoid base 1-phosphates to ethanolamine phosphate (EP), hexadecanal (C16:0al) and hexadecenal (C16:1al). This pathway has been updated with information from Lipidmaps>Sphingolipids [1]. Metabolites and proteins from this pathway are coloured orange and have a rounded rectangle shape (where an oval shape indicates that the node only occures in the LipidMaps pathway). Reactions occurring in the lipidmaps pathways are coloured orange (where a dashed line indicates that the reaction only occures in the LipidMaps pathway).

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Ontology Terms

 

Bibliography

  1. Merrill AH Jr, Stokes TH, Momin A, Park H, Portz BJ, Kelly S, Wang E, Sullards MC, Wang MD; ''Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease.''; J Lipid Res, 2009 PubMed Europe PMC Scholia
  2. Hannun YA, Obeid LM; ''Principles of bioactive lipid signalling: lessons from sphingolipids.''; Nature reviews Molecular cell biology, 2008 PubMed Europe PMC Scholia
  3. Merrill AH Jr, Wang MD, Park M, Sullards MC; ''(Glyco)sphingolipidology: an amazing challenge and opportunity for systems biology.''; Trends Biochem Sci, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
118359view13:39, 27 May 2021Marvin M2added ref link
118355view13:35, 27 May 2021Marvin M2added pubmed for ref
110178view14:12, 23 April 2020EgonwRemoved a redundant and broken reference.
106689view13:00, 17 September 2019MaintBotHMDB identifier normalization
105103view12:39, 8 July 2019DeSlChanged wikidata IDs for genes to uniprot or Ensembl.
102322view08:19, 20 December 2018FehrhartChanged title due to overlap with other pathway
101821view07:55, 11 November 2018EgonwTwo more changes of "Ensembl Human" to "Ensembl".
101820view22:52, 10 November 2018LarsEijssenChanged the database for the primary annotation of CERT from 'Ensembl Human' to 'Ensembl'. After the change, the cross references are properly shown.
98570view15:36, 17 September 2018DeSlRemoved "last modified" item
98569view15:35, 17 September 2018DeSlModified description
98568view15:34, 17 September 2018DeSlChanged layout, added info from LipidMaps
97394view06:23, 14 May 2018EgonwSGMS2 and GlcCer are also proteins
97393view06:21, 14 May 2018EgonwSGMS1 is a gene product.
97383view17:52, 13 May 2018EgonwFixed the protein to type Protein.
95422view15:19, 14 December 2017DeSlAdded ID for ASAH3
95021view07:52, 1 November 2017EgonwFixed a data source.
94434view10:53, 8 September 2017DeSlAnnotated several nodes.
94433view10:51, 8 September 2017DeSlannotated several nodes.
94426view10:04, 7 September 2017DeSlChanged location of title.
94425view10:03, 7 September 2017DeSlConnected glucosylceramidase enzymes
94424view09:59, 7 September 2017DeSlChanged location of title.
94423view09:58, 7 September 2017DeSlAdded all reverse reactions to this PW, annotated several nodes.
94384view11:40, 6 September 2017DeSlChanged all lines for enzymes to MIM catalysis, changed all lines between metabolite nodes to MIM conversion. Still have to connect (DH)Cer synthases in PW. Will look at literature for that.
94372view13:12, 4 September 2017DeSlAdded information from lit. ref. to PW (inhibition by fumonisins B1)
94291view15:29, 31 August 2017DeSlQuick edit to datanode annotation or property
94111view12:05, 21 August 2017DeSlAdded decription for metabolite node abbreviations.
94110view11:52, 21 August 2017DeSlChanged appaerence of other groups of genes/proteins.
94109view11:50, 21 August 2017DeSlAdded several IDs for metabolites (lipids, example C16). Changed appaerence of several gene groups, which where shifted.
93688view14:13, 9 August 2017DeSlChanged faulty ChEBi ID(same was used for GalCer and GlcCer); added to other metaboolite IDs (previously not annotated).
79871view14:51, 21 April 2015Mkutmonfixed id for "Ethanolamine phosphate"
78591view14:51, 7 January 2015MaintBotadded missing graphIds
71368view18:37, 17 October 2013MaintBotAutomated update of data sources
71248view20:24, 16 October 2013MaintBotAutomated update of data sources
70115view19:13, 12 July 2013MaintBotupdated to 2013 schema
69398view18:59, 8 July 2013EgonwReplaced an outdated HMDB identifier with the 3.5 one.
68699view06:56, 6 July 2013EgonwRemoved HMDB as data source where no identifier was given.
59452view20:28, 27 February 2013Khanspersdatanode annotation
59451view20:24, 27 February 2013Khanspersfinal edits
59450view20:23, 27 February 2013Khansperswork in progress
59449view20:06, 27 February 2013Khansperswork in progress
59448view20:04, 27 February 2013Khansperswork in progress
59447view20:01, 27 February 2013Khansperswork in progress
59411view22:31, 26 February 2013MaintBotwork in progress
59410view22:27, 26 February 2013MaintBotPeriodical save, work in progress
59409view22:11, 26 February 2013MaintBotwork in progress
59408view22:09, 26 February 2013MaintBotPeriodical save, work in progress
59407view21:58, 26 February 2013MaintBotPeriodical save, work in progress
59404view21:48, 26 February 2013MaintBotPeriodical save, work in progress
59403view21:43, 26 February 2013MaintBotwork in progress
59402view21:38, 26 February 2013MaintBotPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3-ketodihydroshpingosineMetaboliteQ27109281 (Wikidata)
3-ketosphinganineMetaboliteCHEBI:17862 (ChEBI)
ACER1GeneProductENSG00000167769 (Ensembl) (dihydro)ceramide synthases. ASAH3 is old name of ACER1
ASAH1GeneProduct427 (Entrez Gene) (dihydro)ceramide synthases
ASAH2GeneProduct56624 (Entrez Gene)
B4GALT6GeneProduct9331 (Entrez Gene)
C16:0-alMetabolite
C16:1-alMetabolite
CDaseProtein3.5.1.23 (Enzyme Nomenclature) Ceramidase
CERKGeneProduct64781 (Entrez Gene) 2.7.1.138
CERTGeneProductENSG00000113163 (Ensembl)
Cer1PMetaboliteCHEBI:13956 (ChEBI)
CerS1GeneProduct57515 (Entrez Gene) 2.3.1.24
CerS2GeneProduct29956 (Entrez Gene)
CerS3GeneProduct204219 (Entrez Gene)
CerS4GeneProduct79603 (Entrez Gene)
CerS5GeneProduct91012 (Entrez Gene)
CerS6GeneProduct253782 (Entrez Gene)
CeramidesMetaboliteHMDB0004949 (HMDB)
CoA(16:0)Metabolite
CoA(18:0)Metabolite
CoA(20:0)Metabolite
CoA(22:0)Metabolite
CoA(24:0)Metabolite
CoA(24:1)Metabolite
CoA(26:0)Metabolite
CoA(26:1)Metabolite
DEGS1MetaboliteQ21105760 (Wikidata)
DEGS2MetaboliteQ21115762 (Wikidata)
DHCer1PMetaboliteQ37611218 (Wikidata) C16 Dihydroceramide-1-Phosphate
DHGalCerMetaboliteC16 Dihydro-GalactoCerebroside
DHGlcCerMetaboliteLMSP0501AA04 (LIPID MAPS) C16 Dihydro-Glucosyl- ceramide
DHLacCerMetaboliteLMSP0501AB14 (LIPID MAPS) C16 DihydroLactosylceramide
DHSMMetaboliteLMSP030100A0 (LIPID MAPS) dihydrosphingomyelin
DHSTMetaboliteWhere does this abbreviation stand for? dihydrosterigmatocystin?!
Dihydroceramide desaturaseMetaboliteQ17117943 (Wikidata)
DihydroceramideMetaboliteHMDB0006752 (HMDB)
DihydrosphingosineMetaboliteQ27088847 (Wikidata)
Ethanolamine phosphateMetaboliteCHEBI:17553 (ChEBI)
FVT1GeneProduct2531 (Entrez Gene) 1.1.1.102
Fumonisins B1MetaboliteQ420762 (Wikidata)
GAL3ST1GeneProduct9514 (Entrez Gene)
GBA2Protein57704 (Entrez Gene) protein phosphatase 2A (PP2A)
GBAProtein2629 (Entrez Gene) protein phosphatase 1 (PP1)
GalCer synthaseProteinENSG00000174607 (Ensembl) UGT8 / CGT
GalCerMetaboliteCHEBI:36498 (ChEBI)
GlcCer synthaseProteinQ16739 (Uniprot-TrEMBL) glucosylceramide synthase (GCS)
GlcCerMetaboliteHMDB0000140 (HMDB) Glucosylceramide
GlucosylceramidaseProtein3.2.1.45 (Enzyme Nomenclature) Glucosylceramidase
KDSRGeneProductENSG00000119537 (Ensembl) 3-ketodihydrosphingosine reductase
LactosylceramideMetaboliteHMDB0006750 (HMDB)
PP1Protein5499 (Entrez Gene) protein phosphatase 1 (PP1)
PP2AProtein5515 (Entrez Gene) protein phosphatase 2A (PP2A)
PPAP2AGeneProduct8611 (Entrez Gene)
Palmityl-CoAMetaboliteHMDB0001338 (HMDB)
PhosphataseProtein3.1.3.16 (Enzyme Nomenclature) protein-serine/threonine phosphatase
S1P lyaseProtein4.1.2.27 (Enzyme Nomenclature) sphingosine-1-phosphate (S1P) lyase
SGMS1GeneProductENSG00000198964 (Ensembl) Sphingomyelin synthase 1
SGMS2ProteinQ8NHU3 (Uniprot-TrEMBL) Sphingomyelin synthase 2
SGPL1GeneProductENSG00000166224 (Ensembl) sphinganine-1-phosphate
SGPP2GeneProduct130367 (Entrez Gene)
SMS1ProteinQ86VZ5 (Uniprot-TrEMBL) 2.7.8.3
SMS2ProteinQ8NHU3 (Uniprot-TrEMBL) 2.7.8.3
SPHK1GeneProduct8877 (Entrez Gene)
SPHK2GeneProduct56848 (Entrez Gene)
SPT1GeneProduct10558 (Entrez Gene)
SPT2GeneProduct9517 (Entrez Gene) 2.3.1.50
SPT3GeneProduct55304 (Entrez Gene)
Sa 1-phosphateMetaboliteHMDB0001383 (HMDB) sphinganine-1-phosphate
SerineMetaboliteHMDB0000187 (HMDB)
SoP lyase1GeneProduct4.1.2.27 (Enzyme Nomenclature) 4.1.2.27
SphinganineMetaboliteHMDB0000269 (HMDB)
SphingomyelinMetaboliteHMDB0001348 (HMDB)
Sphingosine 1-phosphateMetaboliteHMDB0000277 (HMDB)
SphingosineMetaboliteHMDB0000252 (HMDB)
SulfatideMetaboliteHMDB0000024 (HMDB)

Annotated Interactions

No annotated interactions

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