Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRX9AV)

• DTT Name: Sortilin (SORT1)
• Synonyms: 100 kDa NT receptor; Glycoprotein 95; Gp95; Neurotensin receptor 3; NT3; NTR3
• Gene Name: SORT1
• DTT Type: Clinical trial target; [1]
• UniProt ID: SORT_HUMAN
• TTD ID: T63233
• Sequence:
  MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGL
  RAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDS
  TGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSG
  KVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLW
  VSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIG
  VKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDM
  VFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLS
  EDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLS
  EPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHS
  SRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSY
  TIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVT
  KQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPG
  DKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKK
  YVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE
• Function: Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:16787399). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi. {ECO:0000269|PubMed:10085125, ECO:0000269|PubMed:11331584, ECO:0000269|PubMed:11390366, ECO:0000269|PubMed:12209882, ECO:0000269|PubMed:12598608, ECO:0000269|PubMed:14657016, ECO:0000269|PubMed:14985763, ECO:0000269|PubMed:15313463, ECO:0000269|PubMed:15930396, ECO:0000269|PubMed:15987945, ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:18817523}.
• KEGG Pathway: 6272 (hsa)
• Reactome Pathway: (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AL001	DM7YBGH	Frontotemporal dementia	6D83	Phase 3	[2]
GSK4527223	DMXLD07	Frontotemporal dementia	6D83	Phase 3	[1]
GSK4527226	DMOVMGA	Neurodegenerative disorder	8A20-8A23	Phase 1	[1]

References

• [1] Clinical pipeline report, company report or official report of GlaxoSmithKline
• [2] Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia. J Transl Med. 2023 Jun 15;21(1):387.