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Target intelligence / Profile preview
Seizure-related 6 homolog protein (SEZ6) (SEZ6)
- Target
- SEZ6
- Molecular classification
- Transmembrane protein
01
Overview
Seizure-related 6 homolog protein (SEZ6) is a cell surface type 1 transmembrane glycoprotein with CUB, CCP, and sushi-like domains, primarily expressed in neuronal cells. It regulates kainate receptor (GluK2/3) trafficking, glycosylation (including HNK-1 glycan), and surface localization in the secretory pathway, independent of BACE1 cleavage. SEZ6 is a BACE1 substrate, undergoes ectodomain shedding, and influences dendritic spine dynamics and LTP. In cancer, it is selectively overexpressed in high-grade neuroendocrine tumors like SCLC (78% of cases), LCNEC, and neuroendocrine prostate cancer, often linked to ASCL1-driven neuroendocrine differentiation, positioning it as a tumor-selective ADC target with promising preclinical antitumor activity.
- Other names
- seizure protein 6SEZ6
02
Mechanism of action
Antibody-drug conjugate-mediated antitumor activity
03
Biological functions
Neuronal developmentkainate receptor trafficking and glycosylationmodulation of kainate receptor surface localizationinhibition of complement cascade
04
Disease associations
Neuroendocrine malignancies (e.g., SCLC)Alzheimer's diseasepsychiatric disorderscancer stem cell-related angiogenesis
05
Safety considerations
Limited normal tissue expression outside CNSpotential complement inhibition effects
06
Interacting drugs
SEZ6-targeted antibody-drug conjugates (ADCs)
07
Biomarkers
SEZ6 expression by IHCASCL1-positive neuroendocrine-high tumors
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