Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOT2RY)

• DTT Name: Sequestosome-1 p62 (SQSTM1)
• Synonyms: Ubiquitin-binding protein p62; Sequestosome-1; Phosphotyrosine-independent ligand for the Lck SH2 domain of 62kDa; Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa; OSIL; ORCA; EBIAP; EBI3-associated protein of 60 kDa
• Gene Name: SQSTM1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Zinc-finger
• UniProt ID: SQSTM_HUMAN
• TTD ID: T17367
• Sequence:
  MASLTVKAYLLGKEDAAREIRRFSFCCSPEPEAEAEAAAGPGPCERLLSRVAALFPALRP
  GGFQAHYRDEDGDLVAFSSDEELTMAMSYVKDDIFRIYIKEKKECRRDHRPPCAQEAPRN
  MVHPNVICDGCNGPVVGTRYKCSVCPDYDLCSVCEGKGLHRGHTKLAFPSPFGHLSEGFS
  HSRWLRKVKHGHFGWPGWEMGPPGNWSPRPPRAGEARPGPTAESASGPSEDPSVNFLKNV
  GESVAAALSPLGIEVDIDVEHGGKRSRLTPVSPESSSTEEKSSSQPSSCCSDPSKPGGNV
  EGATQSLAEQMRKIALESEGRPEEQMESDNCSGGDDDWTHLSSKEVDPSTGELQSLQMPE
  SEGPSSLDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFSDEGGWLTRLLQTK
  NYDIGAALDTIQYSKHPPPL
• Function: Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Promotes relocalization of 'Lys-63'-linked ubiquitinated TMEM173/STING to autophagosomes. Autophagy receptor required for selective macroautophagy (aggrephagy).
• KEGG Pathway: Osteoclast differentiation (hsa04380)
• Reactome Pathway:
  p75NTR recruits signalling complexes (R-HSA-209543)
  NF-kB is activated and signals survival (R-HSA-209560)
  Interleukin-1 signaling (R-HSA-446652)
  NRIF signals cell death from the nucleus (R-HSA-205043)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IMX-942	DMV5KSA	Mucositis	CA00	Preclinical	[1]

References

• [1] Clinical pipeline report, company report or official report of SARomics Biostructures.