SREBP (HLH106) is the single Drosophila sterol regulatory element-binding protein, a membrane-bound basic helix-loop-helix leucine zipper transcription factor. The precursor resides in the ER membrane in a complex with SCAP; when membrane phosphatidylethanolamine is low, it is transported to the Golgi and sequentially cleaved, releasing the N-terminal bHLH-Zip domain, which enters the nucleus, binds sterol regulatory elements and E-boxes as a dimer, and activates RNA polymerase II transcription of genes for fatty acid and phospholipid synthesis. dSREBP is essential for larval fatty acid synthesis and growth (mutants are fatty acid auxotrophs), and it also influences lipid droplet formation in specific cell types.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: SREBP binds sterol regulatory elements and E-boxes and is an RNA Pol II-specific DNA-binding transcription factor. Reason: Conserved bHLH-Zip function (IBA), supported by direct binding data for HLH106. Supporting Evidence: PMID:9632664 HLH106 binds to both palindromic E-boxes and direct repeat sterol regulatory elements (SREs) efficiently |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: SREBP binds sterol regulatory elements and E-boxes and is an RNA Pol II-specific DNA-binding transcription factor. Reason: Conserved bHLH-Zip function (IBA), supported by direct binding data for HLH106. Supporting Evidence: PMID:9632664 HLH106 binds to both palindromic E-boxes and direct repeat sterol regulatory elements (SREs) efficiently |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:9632664 HLH106, a Drosophila sterol regulatory element-binding prote... | ACCEPT | Summary: The mature N-terminal domain of HLH106 activates transcription from SREs. Reason: Core molecular function shown by reporter assays in Drosophila and mammalian cells. Supporting Evidence: PMID:9632664 The amino-terminal "mature" protein activates transcription from mammalian SREs in both mammalian and Drosophila tissue culture cells. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: The processed SREBP N-terminal fragment is nuclear. Reason: Where the mature transcription factor acts; supported by fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction and a shorter cross-reacting form in the nuclear fraction |
| GO:0005634 nucleus | IDA PMID:9632664 HLH106, a Drosophila sterol regulatory element-binding prote... | ACCEPT | Summary: The processed SREBP N-terminal fragment is nuclear. Reason: Where the mature transcription factor acts; supported by fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction and a shorter cross-reacting form in the nuclear fraction |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The processed SREBP N-terminal fragment is nuclear. Reason: Where the mature transcription factor acts; supported by fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction and a shorter cross-reacting form in the nuclear fraction |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:9632664 HLH106, a Drosophila sterol regulatory element-binding prote... | ACCEPT | Summary: Full-length SREBP precursor is membrane-bound (ER membrane). Reason: Precursor location before processing; direct fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Full-length SREBP precursor is membrane-bound (ER membrane). Reason: Precursor location before processing; direct fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: SREBP regulates (activates) RNA Pol II transcription of lipid synthesis genes. Reason: Consistent with its transcription activator activity and with transcriptional deficits in mutants. Supporting Evidence: PMID:16753579 Mutant larvae exhibit pronounced growth defects prior to lethality, along with substantial deficits in the transcription of genes required for fatty acid synthesis. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:11988566 Regulation of SREBP processing and membrane lipid production... | ACCEPT | Summary: SREBP regulates (activates) RNA Pol II transcription of lipid synthesis genes. Reason: Consistent with its transcription activator activity and with transcriptional deficits in mutants. Supporting Evidence: PMID:16753579 Mutant larvae exhibit pronounced growth defects prior to lethality, along with substantial deficits in the transcription of genes required for fatty acid synthesis. |
| GO:0006631 fatty acid metabolic process | NAS PMID:11988566 Regulation of SREBP processing and membrane lipid production... | ACCEPT | Summary: SREBP controls fatty acid synthesis (NAS). Reason: SREBP is the transcriptional regulator of fatty acid synthesis genes in flies; dSREBP mutants contain markedly less fatty acid. Supporting Evidence: PMID:11988566 exerting feedback control on the synthesis of fatty acids and phospholipids |
| GO:0016020 membrane | IDA PMID:8577739 HLH106, a Drosophila transcription factor with similarity to... | ACCEPT | Summary: Full-length SREBP precursor is membrane-bound (ER membrane). Reason: Precursor location before processing; direct fractionation data. Supporting Evidence: PMID:8577739 we find the full-length gene product in the membrane fraction |
| GO:0031965 nuclear membrane | IDA PMID:9632664 HLH106, a Drosophila sterol regulatory element-binding prote... | KEEP AS NON CORE | Summary: The C-terminal portion of HLH106 localizes to perinuclear membranes when expressed in mammalian cells. Reason: Observed in a heterologous system and consistent with the ER/nuclear envelope continuum; ER membrane is the functional precursor location. Supporting Evidence: PMID:9632664 When expressed in mammalian cells, the carboxyl-terminal portion also localizes to perinuclear membranes similar to mammalian SREBPs. |
| GO:0032933 SREBP signaling pathway | IDA PMID:9632664 HLH106, a Drosophila sterol regulatory element-binding prote... | ACCEPT | Summary: HLH106 is the transcription factor of the SREBP signalling pathway, processed in an SCAP-stimulated fashion. Reason: Core pathway role. Supporting Evidence: PMID:9632664 membrane-bound HLH106 is proteolytically processed in response to intracellular sterol levels in mammalian cells in an SREBP cleavage-activating protein-stimulated fashion |
| GO:0032936 SREBP-SCAP complex | NAS PMID:11988566 Regulation of SREBP processing and membrane lipid production... | ACCEPT | Summary: SREBP is part of the SREBP-SCAP complex. Reason: Conserved complex required for ER-to-Golgi transport of SREBP. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | ACCEPT | Summary: SREBP regulates (activates) RNA Pol II transcription of lipid synthesis genes. Reason: Consistent with its transcription activator activity and with transcriptional deficits in mutants. Supporting Evidence: PMID:16753579 Mutant larvae exhibit pronounced growth defects prior to lethality, along with substantial deficits in the transcription of genes required for fatty acid synthesis. |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | ACCEPT | Summary: Protein dimerization activity inferred from the bHLH-Zip domain. Reason: bHLH-Zip transcription factors bind DNA as dimers; appropriate electronic inference. |
| GO:0055089 fatty acid homeostasis | IMP PMID:16753579 Fatty acid auxotrophy in Drosophila larvae lacking SREBP. | ACCEPT | Summary: dSREBP mutants are fatty acid auxotrophs. Reason: Direct mutant evidence that SREBP maintains fatty acid levels. Supporting Evidence: PMID:16753579 These data indicate that dSREBP deficiency renders Drosophila larvae auxotrophic for fatty acids. file:DROME/SREBP/SREBP-deep-research-falcon.md Loss of dSREBP reduces expression of acetyl-CoA synthase (**ACS**), acetyl-CoA carboxylase (**ACC**), and fatty-acid synthase (**FAS**) |
| GO:0140042 lipid droplet formation | IGI PMID:32913227 The conserved microRNA miR-210 regulates lipid metabolism an... | KEEP AS NON CORE | Summary: Genetic interaction with miR-210 affecting lipid droplet formation in the retina. Reason: Tissue-specific downstream consequence of SREBP-driven lipogenesis. |
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Download this section (compressed HTML)Sterol regulatory element binding protein (SREBP) encodes a membrane protein that functions as a master-regulator of lipogenesis. It activates transcription of lipogenic genes upon reduction of lipid or cholesterol levels.
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