Molecule Information

General Information of the Molecule (ID: Mol04020)

• Name: Ceramide kinase (CERK) ,Homo sapiens
• Synonyms: Acylsphingosine kinase; Lipid kinase 4
• Molecule Type: Protein
• Gene Name: CERK
• Gene ID: 64781
• Location: chr22:46684410-46738252[-]
• Sequence:
  MGATGAAEPLQSVLWVKQQRCAVSLEPARALLRWWRSPGPGAGAPGADACSVPVSEIIAV
  EETDVHGKHQGSGKWQKMEKPYAFTVHCVKRARRHRWKWAQVTFWCPEEQLCHLWLQTLR
  EMLEKLTSRPKHLLVFINPFGGKGQGKRIYERKVAPLFTLASITTDIIVTEHANQAKETL
  YEINIDKYDGIVCVGGDGMFSEVLHGLIGRTQRSAGVDQNHPRAVLVPSSLRIGIIPAGS
  TDCVCYSTVGTSDAETSALHIVVGDSLAMDVSSVHHNSTLLRYSVSLLGYGFYGDIIKDS
  EKKRWLGLARYDFSGLKTFLSHHCYEGTVSFLPAQHTVGSPRDRKPCRAGCFVCRQSKQQ
  LEEEQKKALYGLEAAEDVEEWQVVCGKFLAINATNMSCACRRSPRGLSPAAHLGDGSSDL
  ILIRKCSRFNFLRFLIRHTNQQDQFDFTFVEVYRVKKFQFTSKHMEDEDSDLKEGGKKRF
  GHICSSHPSCCCTVSNSSWNCDGEVLHSPAIEVRVHCQLVRLFARGIEENPKPDSHS
• Function: Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate (PubMed:11956206, PubMed:16269826, PubMed:19168031). Acts efficiently on natural and analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2- ceramide and C6-dihydroceramide, but not on other lipids, such as various sphingosines (PubMed:11956206, PubMed:16269826, PubMed:19168031). Shows a greater preference for D-erythro isomer of ceramides (PubMed:16269826). Binds phosphoinositides (PubMed:19168031). .
• Uniprot ID: CERK1_HUMAN
• Ensembl ID: ENSG00000100422
• HGNC ID: HGNC:19256

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293 T cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: H3396 cells; Breast; Mus musculus (Mouse); CVCL_D348
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Apoptosis rate assay
• Mechanism Description: Mechanistically, the elevated EHF expression transcriptionally up-regulates CERK expression to prohibit tamoxifen-induced sphingolipid ceramide accumulation, which then inhibits tamoxifen-mediated repression on PI3K/AKT dependent cell proliferation and its driven p53/caspase-3 mediated apoptosis in TAMR cells. This work provides insight into the regulation of sphingolipid metabolism in tamoxifen resistance and identifies a potential therapeutic target for this disease.

References

• Ref 1: Ceramide kinase confers tamoxifen resistance in estrogen receptor-positive breast cancer by altering sphingolipid metabolism. Pharmacol Res. 2023 Jan;187:106558.