Human Gene SREBF1 (ENST00000261646.11) from GENCODE V44
Description: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). 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'). (from UniProt P36956) RefSeq Summary (NM_001005291): This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. [provided by RefSeq, Nov 2017]. Gencode Transcript: ENST00000261646.11 Gencode Gene: ENSG00000072310.18 Transcript (Including UTRs) Position: hg38 chr17:17,811,334-17,836,986 Size: 25,653 Total Exon Count: 19 Strand: - Coding Region Position: hg38 chr17:17,812,622-17,836,817 Size: 24,196 Coding Exon Count: 19
ID:SRBP1_HUMAN DESCRIPTION: RecName: Full=Sterol regulatory element-binding protein 1; Short=SREBP-1; AltName: Full=Class D basic helix-loop-helix protein 1; Short=bHLHd1; AltName: Full=Sterol regulatory element-binding transcription factor 1; Contains: RecName: Full=Processed sterol regulatory element-binding protein 1; FUNCTION: Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). 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'). SUBUNIT: Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA. INTERACTION: P45481:Crebbp (xeno); NbExp=2; IntAct=EBI-948328, EBI-296306; Q96RN5:MED15; NbExp=6; IntAct=EBI-948328, EBI-394506; Q96EB6:SIRT1; NbExp=2; IntAct=EBI-948338, EBI-1802965; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cytoplasmic vesicle, COPII-coated vesicle membrane; Multi-pass membrane protein. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols. SUBCELLULAR LOCATION: Processed sterol regulatory element-binding protein 1: Nucleus. TISSUE SPECIFICITY: Expressed in a wide variety of tissues, most abundant in liver and adrenal gland. In fetal tissues lung and liver shows highest expression. Isoform SREBP-1C predominates in liver, adrenal gland and ovary, whereas isoform SREBP-1A predominates in hepatoma cell lines. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, brain, white fat, and muscle. PTM: At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. 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 and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. PTM: Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding (By similarity). SIMILARITY: Belongs to the SREBP family. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SEQUENCE CAUTION: Sequence=AAB28522.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAD92846.1; Type=Miscellaneous discrepancy; Note=Intron retention; WEB RESOURCE: Name=Wikipedia; Note=Sterol regulatory element- binding protein entry; URL="http://en.wikipedia.org/wiki/Sterol_regulatory_element_binding_protein";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P36956
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding GO:0005515 protein binding GO:0019901 protein kinase binding GO:0032810 sterol response element binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0044877 macromolecular complex binding GO:0046983 protein dimerization activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0003062 regulation of heart rate by chemical signal GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006629 lipid metabolic process GO:0007568 aging GO:0007623 circadian rhythm GO:0008202 steroid metabolic process GO:0008203 cholesterol metabolic process GO:0008286 insulin receptor signaling pathway GO:0008610 lipid biosynthetic process GO:0009267 cellular response to starvation GO:0009749 response to glucose GO:0010867 positive regulation of triglyceride biosynthetic process GO:0014070 response to organic cyclic compound GO:0019217 regulation of fatty acid metabolic process GO:0030324 lung development GO:0030522 intracellular receptor signaling pathway GO:0031065 positive regulation of histone deacetylation GO:0031647 regulation of protein stability GO:0032094 response to food GO:0032526 response to retinoic acid GO:0032570 response to progesterone GO:0032869 cellular response to insulin stimulus GO:0033762 response to glucagon GO:0033993 response to lipid GO:0042493 response to drug GO:0042789 mRNA transcription from RNA polymerase II promoter GO:0043434 response to peptide hormone GO:0045444 fat cell differentiation GO:0045540 regulation of cholesterol biosynthetic process GO:0045542 positive regulation of cholesterol biosynthetic process GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046676 negative regulation of insulin secretion GO:0050796 regulation of insulin secretion GO:0051591 response to cAMP GO:0070542 response to fatty acid GO:0071398 cellular response to fatty acid GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1903146 regulation of mitophagy GO:1903214 regulation of protein targeting to mitochondrion
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