Sterol regulatory element-binding proteins (SREBP) signaling (WP1982)

Homo sapiens

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Sterol regulatory element-binding proteins (SREBPs) are membrane-bound proteins that act as transcription factors. They regulate lipid, especially cholesterol, biosynthesis and uptake at a transcriptional level to maintain cellular lipid homeostasis. In addition, SREBP appears to be involved in a variety of other cellular processes. This pathway of SREBP focuses on the regulation of lipid metabolism by SREBP. The data on which this pathway is based, is derived from a variety of in vitro and in vivo studies using different species, including mouse, rat, hamster and human. This pathway served as the basis for a review about SREBP that was published in Genes and Nutrition: [http://www.ncbi.nlm.nih.gov/pubmed/23516131 PubMed]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1982 CPTAC Assay Portal].

Authors

Sabine Daemen , Chris Evelo , Dan Bolser , Martina Summer-Kutmon , Daniela Digles , Zahra Roudbari , Marianthi Kalafati , Egon Willighagen , Kristina Hanspers , Friederike Ehrhart , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

fatty acid biosynthetic pathway sterol regulatory element-binding protein signaling pathway sterol regulatory element-binding protein signaling pathway cholesterol biosynthetic pathway

Disease Ontology

obsolete hypercholesterolemia

Cell Type Ontology

hepatocyte

Participants
Query Drugst.One

Label Type Compact URI Comment
Glucose Metabolite hmdb:HMDB0000122
PUFAs Metabolite chebi:26208 Inhibition of SREBP1 processing
Cholesterol Metabolite hmdb:HMDB0000067
UFAs Metabolite chebi:26208
Glutamine Metabolite hmdb:HMDB0000641
Oxysterols Metabolite chebi:53030
PKA GeneProduct ensembl:ENSG00000072062
SCAP GeneProduct ensembl:ENSG00000114650
CDK8 GeneProduct ensembl:ENSG00000132964
PRKAA2 GeneProduct ensembl:ENSG00000162409
CAMP GeneProduct ensembl:ENSG00000164047
PRKAG2 GeneProduct ensembl:ENSG00000106617
AKT GeneProduct ensembl:ENSG00000142208
gp78 GeneProduct ensembl:ENSG00000159461
PRKAG3 GeneProduct ensembl:ENSG00000115592
importin beta GeneProduct ensembl:ENSG00000108424
SREBP2 GeneProduct ensembl:ENSG00000198911
PI3K GeneProduct ensembl:ENSG00000121879
INSIG1 GeneProduct ensembl:ENSG00000186480
LPIN1 GeneProduct ensembl:ENSG00000134324
LXR GeneProduct ensembl:ENSG00000131408
NFY GeneProduct ensembl:ENSG00000001167
PRKAB2 GeneProduct ensembl:ENSG00000131791
TRC8 GeneProduct ensembl:ENSG00000170881
nSREBP GeneProduct ensembl:ENSG00000072310
ATF6 GeneProduct ensembl:ENSG00000118217
PRKAA1 GeneProduct ensembl:ENSG00000132356
S1P GeneProduct ensembl:ENSG00000140943
FGF21 GeneProduct ensembl:ENSG00000105550
GSK3 GeneProduct ensembl:ENSG00000105723
PRKAB1 GeneProduct ensembl:ENSG00000111725
RBP4 GeneProduct ensembl:ENSG00000138207
PRKAG1 GeneProduct ensembl:ENSG00000181929
mTORC1 GeneProduct ensembl:ENSG00000198793
HMGCR GeneProduct ensembl:ENSG00000113161
SIRT1 GeneProduct ensembl:ENSG00000096717
INSIG2 GeneProduct ensembl:ENSG00000125629
SREBP1a,-c GeneProduct ensembl:ENSG00000072310
SAR1A GeneProduct ensembl:ENSG00000079332
SAR1B GeneProduct ensembl:ENSG00000152700
SEC23A GeneProduct ensembl:ENSG00000100934
SEC23B GeneProduct ensembl:ENSG00000101310
SEC24A GeneProduct ensembl:ENSG00000113615
SEC24B GeneProduct ensembl:ENSG00000138802
SEC24C GeneProduct ensembl:ENSG00000176986
SEC24D GeneProduct ensembl:ENSG00000150961
SEC13 GeneProduct ensembl:ENSG00000157020
SEC31A GeneProduct ensembl:ENSG00000138674
SEC31B GeneProduct ensembl:ENSG00000075826
SREBF2 GeneProduct ensembl:ENSG00000198911
S2P GeneProduct ensembl:ENSG00000012174
nSREBP1a,-c GeneProduct ensembl:ENSG00000072310
nSREBP2 GeneProduct ensembl:ENSG00000198911
CREB GeneProduct ensembl:ENSG00000118260
SP1 GeneProduct ensembl:ENSG00000185591
YY1 GeneProduct ensembl:ENSG00000100811
PGC-1beta GeneProduct ensembl:ENSG00000155846
ARC105 GeneProduct ensembl:ENSG00000099917 activator recruited cofactor (ARC)-mediator activator complex
LSS GeneProduct ensembl:ENSG00000160285
HMGCS GeneProduct ensembl:ENSG00000112972
MVD GeneProduct ensembl:ENSG00000167508
IDI GeneProduct ensembl:ENSG00000067064
FDPS GeneProduct ensembl:ENSG00000160752
FDFT GeneProduct ensembl:ENSG00000079459
SQLE GeneProduct ensembl:ENSG00000104549
CYP51A1 GeneProduct ensembl:ENSG00000001630
LPL GeneProduct ensembl:ENSG00000175445
LDLR GeneProduct ensembl:ENSG00000130164
SCARB1 GeneProduct ensembl:ENSG00000073060
ACACA GeneProduct ensembl:ENSG00000278540
GPA GeneProduct ensembl:ENSG00000119927
FASN GeneProduct ensembl:ENSG00000169710
DBI GeneProduct ensembl:ENSG00000155368
ACLY GeneProduct ensembl:ENSG00000131473
MDH GeneProduct ensembl:ENSG00000014641
PPARG GeneProduct ensembl:ENSG00000132170
ACS GeneProduct ensembl:ENSG00000154930
SCD GeneProduct ensembl:ENSG00000099194
Insulin Protein uniprot:P01308

References

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  2. Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies. Sakai J, Nohturfft A, Goldstein JL, Brown MS. J Biol Chem. 1998 Mar 6;273(10):5785–93. PubMed Europe PMC Scholia
  3. Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein. Bennett MK, Ngo TT, Athanikar JN, Rosenfeld JM, Osborne TF. J Biol Chem. 1999 May 7;274(19):13025–32. PubMed Europe PMC Scholia
  4. YY1 is a negative regulator of transcription of three sterol regulatory element-binding protein-responsive genes. Ericsson J, Usheva A, Edwards PA. J Biol Chem. 1999 May 14;274(20):14508–13. PubMed Europe PMC Scholia
  5. Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip. Nagoshi E, Imamoto N, Sato R, Yoneda Y. Mol Biol Cell. 1999 Jul;10(7):2221–33. PubMed Europe PMC Scholia
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  18. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, et al. Nature. 2006 Aug 10;442(7103):700–4. PubMed Europe PMC Scholia
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  20. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. Lee JN, Song B, DeBose-Boyd RA, Ye J. J Biol Chem. 2006 Dec 22;281(51):39308–15. PubMed Europe PMC Scholia
  21. Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver. Yamamoto T, Shimano H, Inoue N, Nakagawa Y, Matsuzaka T, Takahashi A, et al. J Biol Chem. 2007 Apr 20;282(16):11687–95. PubMed Europe PMC Scholia
  22. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6511–8. PubMed Europe PMC Scholia
  23. Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step. Lee JN, Zhang X, Feramisco JD, Gong Y, Ye J. J Biol Chem. 2008 Nov 28;283(48):33772–83. PubMed Europe PMC Scholia
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