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SREBF1 phospho S439

Domain

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Function

Sterol regulatory element-binding protein 1

Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (By similarity).

Processed sterol regulatory element-binding protein 1

Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:12177166, PubMed:32322062, PubMed:8402897). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897).

Isoform SREBP-1A

Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity).

Isoform SREBP-1C

Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity).

Isoform SREBP-1aDelta

The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.

Isoform SREBP-1cDelta

The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.

Involvement in disease

IFAP syndrome 2

IFAP2

An autosomal dominant form of IFAP syndrome, a disease characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. IFAP2 patients manifest ichthyosis follicularis or follicular hyperkeratosis, hyperkeratotic plaques, sparse to no body hair, and photophobia with punctate corneal epithelial defects, corneal pannus, and complicated cataract. Ultrastructural hair analysis shows trichorrhexis nodosa.

None

The disease is caused by variants affecting the gene represented in this entry.

Mucoepithelial dysplasia, hereditary

HMD

An autosomal dominant genodermatosis mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Sterol regulatory element-binding protein 1

Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:32322062, PubMed:8626610). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:32322062, PubMed:8626610). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:32322062, PubMed:8626610). The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane (PubMed:32322062).

Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression (By similarity). Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding (By similarity).

Processed sterol regulatory element-binding protein 1

Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.

Sequence similarities

Belongs to the SREBP family.

Tissue specificity

Expressed in a wide variety of tissues, most abundant in liver and adrenal gland (PubMed:8402897). In fetal tissues lung and liver shows highest expression (PubMed:8402897).

Isoform SREBP-1A

Predominates in hepatoma cell lines (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).

Isoform SREBP-1C

Predominantly expressed in liver and adipose tissues (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).

Cellular localization

  • Sterol regulatory element-binding protein 1
  • Endoplasmic reticulum membrane
  • Multi-pass membrane protein
  • Golgi apparatus membrane
  • Multi-pass membrane protein
  • Cytoplasmic vesicle
  • COPII-coated vesicle membrane
  • Multi-pass membrane protein
  • At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum. Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed.
  • Processed sterol regulatory element-binding protein 1
  • Nucleus
  • Isoform SREBP-1aDelta
  • Nucleus
  • Isoform SREBP-1cDelta
  • Nucleus

Alternative names

BHLHD1, SREBP1, SREBF1, Sterol regulatory element-binding protein 1, SREBP-1, Class D basic helix-loop-helix protein 1, Sterol regulatory element-binding transcription factor 1, bHLHd1

Target type

Proteins

Primary research area

Metabolism

Molecular weight

121675Da

We found 2 products in 1 category

Primary Antibodies

Target

Application

Reactive species

Search our catalogue for 'SREBF1 phospho S439' (2)

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