Molecule Information

General Information of the Molecule (ID: Mol01988)

• Name: Tribbles homolog 3 (TRIB3) ,Mus musculus
• Synonyms: Trib3; Nipk; Trb3
• Molecule Type: Protein
• Gene Name: TRIB3
• Gene ID: 228775
• Location: chr2:152,179,342-152,185,952[-]
• Sequence:
  MRATPLAASADVSCRKKPLEFDDNIDAKCPVLKRVRDEPEPGPLPSLLPPSPPPASDLSP
  AVAPATRLGPYILLEREQGSCSYRALHCPTGTEYTCKVYPASEAQAVLAPYARLPTHQHV
  ARPTEVLLGSRLLYIFFTKTHGDLHSLVRSRRGIPESEAAGLFRQMASAVAHCHKHGLVL
  RDLKLRRFVFSNCERTKLVLENLEDACVMTGSDDSLWDKHACPAYVGPEILSSRPSYSGK
  AADVWSLGVALFTMLAGRYPFHDSEPVLLFGKIRRGTFALPEGLSAPARCLIRCLLRKEP
  SERLVALGILLHPWLREDHGRVSPPQSDRREMDQVVPDGPQLEEAEEGEVGLYG
• Function: Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity. Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. Can inhibit APOBEC3A editing of nuclear DNA.
• Uniprot ID: TRIB3_MOUSE
• Ensembl ID: ENSMUSG00000032715

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Nicorandil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Insulin-resistance syndrome [1]

• Sensitive Disease: Insulin-resistance syndrome [ICD-11: 5A44.0]
• Sensitive Drug: Nicorandil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: PERK signaling pathway; Inhibition; hsa04137
• In Vitro Model: L6 cells; Skeletal muscle; Rattus norvegicus (Rat); CVCL_0385
• In Vivo Model: Adult Sprague-Dawley rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Glucose tolerance test, insulin tolerance test
• Mechanism Description: Nicorandil attenuates high glucose-induced insulin resistance by suppressing oxidative stress-mediated ER stress PERK signaling pathway.

References

• Ref 1: Nicorandil attenuates high glucose-induced insulin resistance by suppressing oxidative stress-mediated ER stress PERK signaling pathway .BMJ Open Diabetes Res Care. 2021 Apr;9(1):e001884. doi: 10.1136/bmjdrc-2020-001884. 10.1136/bmjdrc-2020-001884