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Guanine nucleotide-exchange factor SEC12 (PREB)
- Target
- PREB
- Molecular classification
- Guanine nucleotide-exchange factor (GEF), Enzyme, Transmembrane protein, Transcription factor (in some species, primarily in mammals), ER membrane protein
01
Overview
Guanine nucleotide-exchange factor SEC12 (PREB) is an essential enzyme that catalyzes the exchange of GDP for GTP specifically on the small GTPase Sar1, which is the initiating step for the assembly of the COPII coat required for vesicle budding from the endoplasmic reticulum (ER) to the Golgi apparatus[1][2][3][4][6]. SEC12 is a transmembrane glycoprotein localized to the ER membrane, and its cytosolic domain contains a WD repeat β-propeller structure that directly activates Sar1[3][4]. In yeast, SEC12 is essential for the secretory pathway; in mammals, its homolog is referred to as PREB and may also act as a transcriptional regulator for the prolactin (PRL) gene by binding to the Pit1 element of the PRL promoter[5]. Mutations in SEC12 disrupt ER-to-Golgi trafficking, though no specific drug interactions or disease biomarkers are currently documented. The protein’s role is conserved from yeast to mammals, underscoring its fundamental importance in vesicular transport.
- Other names
- Prolactin regulatory element-binding proteinPREBSEC12Mammalian guanine nucleotide exchange factor mSec12Guanine nucleotide-exchange factor SEC12
02
Mechanism of action
null (no approved drugs act directly on SEC12/PREB)
03
Biological functions
Activation of Sar1 GTPase on the endoplasmic reticulum (ER) membraneInitiation of COPII vesicle formation for ER-to-Golgi transportProtein cargo selection (indirect, downstream via COPII pathway)Binds Pit1-binding element of prolactin promoter (transcriptional regulation in mammals)
04
Disease associations
Other (No direct disease association is strongly established; however, defects in ER-to-Golgi trafficking can contribute to secretory pathway diseases and general cellular dysfunction. Limited data on direct PREB/SEC12 disease roles.)Potential role in prolactin regulation with endocrinological implications (mammalian PREB subtype)
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