SREBP1a

SREBP1a, or Sterol Regulatory Element-Binding Protein 1a, is a transcription factor of the SREBP family that regulates lipid biosynthesis. It is produced from the SREBF1 gene by alternative promoter usage and splicing, yielding two major isoforms: SREBP1a and SREBP1c. SREBP1a is the longer isoform and generally acts as a stronger transcriptional activator than SREBP1c, which is more specialized for insulin-responsive fatty acid synthesis.

SREBP1a is expressed in tissues with high lipogenic capacity, such as liver and intestine, and its relative abundance can vary with developmental stage and physiological conditions. The protein is synthesized as an inactive, membrane-bound precursor anchored in the endoplasmic reticulum. When cellular sterol levels decline, the SCAP-SREBP complex moves to the Golgi, where proteases site-1 and site-2 (S1P and S2P) cleave SREBP1a to release the N-terminal transcription factor. The active fragment then translocates to the nucleus.

In the nucleus, SREBP1a binds sterol regulatory elements in promoters of target genes to activate transcription. Its targets include genes involved in cholesterol and fatty acid biosynthesis, such as HMG-CoA reductase, HMG-CoA synthase, fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase (SCD). Compared with SREBP1c, SREBP1a has a stronger transcriptional activation domain and can induce a broader lipogenic program.

Dysregulation of SREBP1a has been linked to metabolic disorders and certain cancers where increased lipogenesis supports rapid cell growth. See also SREBF1 and the broader SREBP family.