Molecule Information

General Information of the Molecule (ID: Mol04029)

• Name: Early growth response protein 1 (EGR1) ,Homo sapiens
• Synonyms: AT225; Nerve growth factor-induced protein A; Transcription factor ETR103; Transcription factor Zif268; Zinc finger protein 225; Zinc finger protein Krox-24
• Molecule Type: Protein
• Gene Name: EGR1
• Gene ID: 1958
• Location: chr5:138465479-138469303[+]
• Sequence:
  MAAAKAEMQLMSPLQISDPFGSFPHSPTMDNYPKLEEMMLLSNGAPQFLGAAGAPEGSGS
  NSSSSSSGGGGGGGGGSNSSSSSSTFNPQADTGEQPYEHLTAESFPDISLNNEKVLVETS
  YPSQTTRLPPITYTGRFSLEPAPNSGNTLWPEPLFSLVSGLVSMTNPPASSSSAPSPAAS
  SASASQSPPLSCAVPSNDSSPIYSAAPTFPTPNTDIFPEPQSQAFPGSAGTALQYPPPAY
  PAAKGGFQVPMIPDYLFPQQQGDLGLGTPDQKPFQGLESRTQQPSLTPLSTIKAFATQSG
  SQDLKALNTSYQSQLIKPSRMRKYPNRPSKTPPHERPYACPVESCDRRFSRSDELTRHIR
  IHTGQKPFQCRICMRNFSRSDHLTTHIRTHTGEKPFACDICGRKFARSDERKRHTKIHLR
  QKDKKADKSVVASSATSSLSSYPSPVATSYPSPVTTSYPSPATTSYPSPVPTSFSSPGSS
  TYPSPVHSGFPSPSVATTYSSVPPAFPAQVSSFPSSAVTNSFSASTGLSDMTATFSPRTI
  EIC
• 3D-structure: PDB ID: 4R2A; Classification: Dna binding protein/dna; Method: X-ray diffraction; Resolution: 1.59 Å
• Function: Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed:25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). .
• Uniprot ID: EGR1_HUMAN
• Ensembl ID: ENSG00000120738
• HGNC ID: HGNC:3238

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

Ibrutinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Mantle cell lymphoma [ICD-11: 2A85.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Ibrutinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Mice, with fresh tissue from patient; Mice
• Experiment for Molecule Alteration: RNA seq
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of EGR1 in ibrutinib-resistant cells is likely to result from the transcription factor TCF4-mediated EGR1 transcription and EGR1 self-regulation. Genetic and pharmacological inhibition of EGR1 restores the sensitivity of the resistant cells to ibrutinib, suggesting a role EGR1 plays in ibrutinib resistance. The underlying mechanism is that EGR1 mediates metabolic reprogramming to mitochondrial OXPHOS by transcriptional activation of PDP1, which increases ATP production.

References

• Ref 1: EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma. Blood. 2023 Nov 30;142(22):1879-1894.