Molecule Information

General Information of the Molecule (ID: Mol04315)

• Name: Glucocorticoid receptor (NR3C1) ,Homo sapiens
• Synonyms: Nuclear receptor subfamily 3 group C member 1
• Molecule Type: Protein
• Gene Name: NR3C1
• Gene ID: 2908
• Sequence:
  MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
  LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDL
  K LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNG
  GN VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLL
  EGN SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEK
  LGTV YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIP
  PIPVG SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATT
  GPPPKL CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNC
  PACRYRK CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTL
  VSLLEVIE PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDD
  QMTLLQYSW MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVS
  SELHRLQVSY EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSS
  QNWQRFYQLTK LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGN
  IKKLLFHQK
• Function: Receptor for glucocorticoids . Has a dual mode of action: as a transcription factorthat binds to glucocorticoid response elements , both for nuclearand mitochondrial DNA, and as a modulator of other transcriptionfactors . Affects inflammatory responses, cellularproliferation and differentiation in target tissues. Involved inchromatin remodeling . Plays a role in rapid mRNAdegradation by binding to the 5' UTR of target mRNAs and interactingwith PNRC2 in a ligand-dependent manner which recruits the RNA helicaseUPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependenttranscription upon growth hormone stimulation and could reveal anessential role of hepatic GR in the control of body growth . {ECO:0000250|UniProtKB:P06537,ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27120390,ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:37478846,ECO:0000269|PubMed:9590696}.; [Isoform Alpha]: Has transcriptional activation andrepression activity . Mediates glucocorticoid-inducedapoptosis . Promotes accurate chromosome segregationduring mitosis . May act as a tumor suppressor. May play a negative role in adipogenesis through theregulation of lipolytic and antilipogenic gene expression . {ECO:0000250|UniProtKB:P06537,ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988,ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946,ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771,ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385,ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903,ECO:0000269|PubMed:25847991}.; [Isoform Beta]: Acts as a dominant negative inhibitor ofisoform Alpha . Hasintrinsic transcriptional activity independent of isoform Alpha whenboth isoforms are coexpressed . Losesthis transcription modulator function on its own . Hasno hormone-binding activity . May play a role incontrolling glucose metabolism by maintaining insulin sensitivity . Reduces hepatic gluconeogenesis through down-regulation ofPEPCK in an isoform Alpha-dependent manner . Directlyregulates STAT1 expression in isoform Alpha-independent manner. {ECO:0000250|UniProtKB:P06537,ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466,ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088,ECO:0000269|PubMed:8621628}.; [Isoform Alpha-2]: Has lower transcriptional activationactivity than isoform Alpha. Exerts a dominant negative effect onisoform Alpha trans-repression mechanism .; [Isoform GR-P]: Increases activity of isoform Alpha.{ECO:0000269|PubMed:11358809}.; [Isoform Alpha-B]: More effective than isoform Alpha intranscriptional activation, but not repression activity.{ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}.; [Isoform 10]: Has transcriptional activation activity.{ECO:0000269|PubMed:20484466}.; [Isoform Alpha-C1]: Has transcriptional activation activity.{ECO:0000269|PubMed:15866175}.; [Isoform Alpha-C2]: Has transcriptional activation activity.{ECO:0000269|PubMed:15866175}.; [Isoform Alpha-C3]: Has highest transcriptional activationactivity of all isoforms created by alternative initiation. Has transcriptional repressionactivity . Mediates glucocorticoid-induced apoptosis. {ECO:0000269|PubMed:15866175,ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.; [Isoform Alpha-D1]: Has transcriptional activation activity.{ECO:0000269|PubMed:15866175}.; [Isoform Alpha-D2]: Has transcriptional activation activity.{ECO:0000269|PubMed:15866175}.; [Isoform Alpha-D3]: Has lowest transcriptional activationactivity of all isoforms created by alternative initiation. Has transcriptional repressionactivity . {ECO:0000269|PubMed:15866175,ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.
• Uniprot ID: GCR_HUMAN
• Ensembl ID: ENSG0000011358015
• HGNC ID: HGNC:7978

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

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Idelalisib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: b-lymphoblastic leukemia [ICD-11: 2A70] [1]

• Sensitive Disease: b-lymphoblastic leukemia [ICD-11: 2A70]
• Sensitive Drug: Idelalisib
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Nalm-6 cells; Peripheral blood; Homo sapiens (Human); CVCL_0092
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• In Vitro Model: RCH-ACV cells; Bone marrow; Homo sapiens (Human); CVCL_1851
• Experiment for Molecule Alteration: Gene expression assay; MS analysis; Electrophoretic mobility shift assay; Phospho-GR Western blot assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Through this comprehensive analysis, we discovered growth factor receptor-bound protein 2 (Grb2) as a central interactor bridging the pathways related to PI3Kalpha and beta1 integrin.

References

• Ref 1: PI3Kdelta Inhibition Potentiates Glucocorticoids in B-lymphoblastic Leukemia by Decreasing Receptor Phosphorylation and Enhancing Gene Regulation. Cancers (Basel). 2023 Dec 27;16(1):143.