Srebf1 encodes sterol regulatory element-binding protein 1 (SREBP-1; ADD1), a basic helix-loop-helix leucine zipper transcription factor made as an inactive precursor anchored in the endoplasmic reticulum membrane by two transmembrane helices. Its C-terminal domain binds the escort protein SCAP. When sterols are low, or when insulin signals through Akt, the SCAP-SREBP-1 complex is packaged into COPII vesicles and carried to the Golgi, where site-1 and site-2 proteases cut it. The released N-terminal bHLH-ZIP fragment enters the nucleus, binds as a dimer to sterol regulatory elements (SRE-1, ATCACCCCAC) and E-boxes (ATCACGTGA) in target promoters, and activates RNA polymerase II transcription. The nuclear form is short-lived and is degraded by the proteasome. Two isoforms arise from alternative first exons. SREBP-1a is a strong activator of both cholesterogenic and lipogenic genes. SREBP-1c (ADD1), the main form in liver and adipose tissue, preferentially activates fatty acid and triglyceride synthesis genes such as FAS, ACC, SCD1, L-pyruvate kinase and S14, and also PCSK9. In rat hepatocytes SREBP-1c transcription is induced by insulin, glucose and LXR and repressed by glucagon/cAMP and polyunsaturated fatty acids, so it links carbohydrate and insulin status to de novo lipogenesis. It has been implicated in hepatic steatosis, including alcoholic fatty liver, and an Srebf1 variant in the spontaneously hypertensive rat affects hepatic cholesterol accumulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of RNA polymerase II transcription, propagated from a mouse Srebf1 phenotype annotation (acts_upstream_of_or_within). Reason: SREBP-1 is a transcriptional activator; its documented direct activity is activation through SREs and E-boxes. Reported decreases in particular transcripts after SREBP-1c gain or loss (for example insulin receptor substrate genes) are indirect consequences of the lipogenic programme, recorded in the source with the acts_upstream_of_or_within qualifier. Repression is not a function of rat SREBP-1. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SOURCE WEAK OR INFERRED Mouse donor row is an acts_upstream_of_or_within phenotype annotation; it records an indirect effect, not a repressor activity. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi membrane: the SCAP-SREBP-1 precursor is transported to the Golgi, where site-1 and site-2 proteases release the transcription factor. Reason: The precursor reaches the Golgi in COPII vesicles and is cleaved there; the Golgi membrane is where the activating proteolysis happens. Shown for rat SREBP-1c in hepatocytes and stated in the curated UniProt record by similarity. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed |
| GO:0000139 Golgi membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Golgi membrane: the SCAP-SREBP-1 precursor is transported to the Golgi, where site-1 and site-2 proteases release the transcription factor. Reason: The precursor reaches the Golgi in COPII vesicles and is cleaved there; the Golgi membrane is where the activating proteolysis happens. Shown for rat SREBP-1c in hepatocytes and stated in the curated UniProt record by similarity. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed |
| GO:0000139 Golgi membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Golgi membrane: the SCAP-SREBP-1 precursor is transported to the Golgi, where site-1 and site-2 proteases release the transcription factor. Reason: The precursor reaches the Golgi in COPII vesicles and is cleaved there; the Golgi membrane is where the activating proteolysis happens. Shown for rat SREBP-1c in hepatocytes and stated in the curated UniProt record by similarity. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | MODIFY | Summary: Transcription cis-regulatory region binding (ISO from mouse). Reason: Correct but less specific than the evidence supports. Nuclear SREBP-1 binds SRE-1 and E-box sequences in RNA polymerase II promoters (FAS, PCSK9, lipogenic genes), so the RNA polymerase II-specific cis-regulatory term GO:0000978, which the gene already carries by IBA and IDA, is the right refinement. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse SREBP-1 binds SREs in Pol II promoters; transfer is sound, the term is only general. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: RNA polymerase II transcription regulatory region sequence-specific DNA binding. Reason: True but general: the bound elements (SRE-1, E-box) are cis-regulatory promoter elements of Pol II genes, so GO:0000978 (a descendant the gene already carries by IBA and IDA) is the precise term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: RNA polymerase II transcription regulatory region sequence-specific DNA binding. Reason: True but general: the bound elements (SRE-1, E-box) are cis-regulatory promoter elements of Pol II genes, so GO:0000978 (a descendant the gene already carries by IBA and IDA) is the precise term. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Human SREBP-1 binds SREs in Pol II promoters; transfer is sound, the term is only general. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding: nuclear SREBP-1 binds SRE-1 and E-box elements in target promoters. Reason: Core DNA-binding activity. Rat ADD1/SREBP1 binds both an E-box and SRE-1 (PMID:7739539); an SREBP-1c responsive element in the PCSK9 promoter was verified (PMID:16407292, abstract only; curator IDA deferred to). The IBA is consistent with the SREBP family node. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding: nuclear SREBP-1 binds SRE-1 and E-box elements in target promoters. Reason: Core DNA-binding activity. Rat ADD1/SREBP1 binds both an E-box and SRE-1 (PMID:7739539); an SREBP-1c responsive element in the PCSK9 promoter was verified (PMID:16407292, abstract only; curator IDA deferred to). The IBA is consistent with the SREBP family node. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding: nuclear SREBP-1 binds SRE-1 and E-box elements in target promoters. Reason: Core DNA-binding activity. Rat ADD1/SREBP1 binds both an E-box and SRE-1 (PMID:7739539); an SREBP-1c responsive element in the PCSK9 promoter was verified (PMID:16407292, abstract only; curator IDA deferred to). The IBA is consistent with the SREBP family node. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding: nuclear SREBP-1 binds SRE-1 and E-box elements in target promoters. Reason: Core DNA-binding activity. Rat ADD1/SREBP1 binds both an E-box and SRE-1 (PMID:7739539); an SREBP-1c responsive element in the PCSK9 promoter was verified (PMID:16407292, abstract only; curator IDA deferred to). The IBA is consistent with the SREBP family node. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107585 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. MGI:MGI:107606 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. PANTHER:PTN002488844 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000120 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. UniProtKB:P36956-PRO_0000314029 SUPPORTS TRANSFER Donor annotations are sound; the activator child term is supported for rat SREBP-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | MODIFY | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: Correct, but SREBP-1 is specifically an activator: rat ADD1/SREBP1 activates transcription through SRE-1 and E-box elements (PMID:7739539, PMID:8336713) and is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). The activator descendant GO:0001228, already on the gene by IDA, is the core MF. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0001221 transcription coregulator binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transcription coregulator binding, propagated from human SREBP-1 (which recruits CBP/p300 and the Mediator subunit MED15 through its acidic activation domain). Reason: Recruitment of coactivators by the N-terminal acidic activation domain is how SREBP-1 activates transcription; the binding is real but is a mechanistic part of the activator function rather than a separate core activity. Supporting Evidence: UniProtKB:P56720 Interacts with CEBPA, the interaction produces a transcriptional synergy |
| GO:0001221 transcription coregulator binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Transcription coregulator binding, propagated from human SREBP-1 (which recruits CBP/p300 and the Mediator subunit MED15 through its acidic activation domain). Reason: Recruitment of coactivators by the N-terminal acidic activation domain is how SREBP-1 activates transcription; the binding is real but is a mechanistic part of the activator function rather than a separate core activity. Supporting Evidence: UniProtKB:P56720 Interacts with CEBPA, the interaction produces a transcriptional synergy |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific: the core activity of nuclear SREBP-1. Reason: Rat ADD1/SREBP1 is a sequence-specific transcriptional activator acting through SRE-1 and E-boxes (PMID:7739539, PMID:8336713). The IDA (PMID:16407292, abstract only) shows SREBP-1c driving PCSK9 promoter activity; this agrees with the rest of the literature and is accepted. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific: the core activity of nuclear SREBP-1. Reason: Rat ADD1/SREBP1 is a sequence-specific transcriptional activator acting through SRE-1 and E-boxes (PMID:7739539, PMID:8336713). The IDA (PMID:16407292, abstract only) shows SREBP-1c driving PCSK9 promoter activity; this agrees with the rest of the literature and is accepted. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific: the core activity of nuclear SREBP-1. Reason: Rat ADD1/SREBP1 is a sequence-specific transcriptional activator acting through SRE-1 and E-boxes (PMID:7739539, PMID:8336713). The IDA (PMID:16407292, abstract only) shows SREBP-1c driving PCSK9 promoter activity; this agrees with the rest of the literature and is accepted. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific: the core activity of nuclear SREBP-1. Reason: Rat ADD1/SREBP1 is a sequence-specific transcriptional activator acting through SRE-1 and E-boxes (PMID:7739539, PMID:8336713). The IDA (PMID:16407292, abstract only) shows SREBP-1c driving PCSK9 promoter activity; this agrees with the rest of the literature and is accepted. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0003062 regulation of heart rate by chemical signal | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of heart rate by chemical signal (mouse ISO, acts_upstream_of_or_within). Reason: Derived from a mouse Srebf1 phenotype on parasympathetic heart-rate control, thought to work through SREBP-1-dependent expression of cardiac signalling genes. This is an indirect physiological consequence of target-gene regulation, not a role of SREBP-1 in heart-rate signalling. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse knockout phenotype; indirect effect of target-gene regulation. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: DNA binding. Reason: True but uninformative for a bHLH-ZIP factor with defined targets. Rat ADD1/SREBP1 binds SRE-1 and E-box motifs in Pol II promoters, so MODIFY to GO:0000978, which the gene already carries. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0003677 DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: DNA binding. Reason: True but uninformative for a bHLH-ZIP factor with defined targets. Rat ADD1/SREBP1 binds SRE-1 and E-box motifs in Pol II promoters, so MODIFY to GO:0000978, which the gene already carries. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER DNA binding by mouse SREBP-1 is well established; the term is only general. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | MODIFY | Summary: DNA binding. Reason: True but uninformative for a bHLH-ZIP factor with defined targets. Rat ADD1/SREBP1 binds SRE-1 and E-box motifs in Pol II promoters, so MODIFY to GO:0000978, which the gene already carries. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:0003682 chromatin binding | IDA PMID:19371623 Honokiol reverses alcoholic fatty liver by inhibiting the ma... | MODIFY | Summary: Chromatin binding, from ChIP-type evidence of nuclear SREBP-1c occupancy of target promoters. Reason: The experimental row (PMID:19371623, abstract only) reports nuclear SREBP-1c binding to SRE and SRE-related sequences of lipogenic target genes in rat H4IIEC3 cells. That is sequence-specific promoter binding, better captured by GO:0000978 (already on the gene) than by generic chromatin binding. The essence of the curator's annotation is kept. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:19371623 the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | MODIFY | Summary: Chromatin binding, from ChIP-type evidence of nuclear SREBP-1c occupancy of target promoters. Reason: The experimental row (PMID:19371623, abstract only) reports nuclear SREBP-1c binding to SRE and SRE-related sequences of lipogenic target genes in rat H4IIEC3 cells. That is sequence-specific promoter binding, better captured by GO:0000978 (already on the gene) than by generic chromatin binding. The essence of the curator's annotation is kept. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:19371623 the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0003682 chromatin binding | ISO GO_REF:0000121 | MODIFY | Summary: Chromatin binding, from ChIP-type evidence of nuclear SREBP-1c occupancy of target promoters. Reason: The experimental row (PMID:19371623, abstract only) reports nuclear SREBP-1c binding to SRE and SRE-related sequences of lipogenic target genes in rat H4IIEC3 cells. That is sequence-specific promoter binding, better captured by GO:0000978 (already on the gene) than by generic chromatin binding. The essence of the curator's annotation is kept. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Chromatin occupancy by mouse SREBP-1 is site-specific promoter binding. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:19371623 the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000107 | MODIFY | Summary: DNA-binding transcription factor activity. Reason: Correct but general. SREBP-1 is a Pol II-specific activator; MODIFY to GO:0001228, which the gene already carries by IDA. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | MODIFY | Summary: DNA-binding transcription factor activity. Reason: Correct but general. SREBP-1 is a Pol II-specific activator; MODIFY to GO:0001228, which the gene already carries by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Human SREBP-1 TF activity is established; the term is only general. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0003700 DNA-binding transcription factor activity | ISS PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | MODIFY | Summary: DNA-binding transcription factor activity. Reason: Correct but general. SREBP-1 is a Pol II-specific activator; MODIFY to GO:0001228, which the gene already carries by IDA. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:8336713 ADD1 can function as a sequence-specific transcriptional activator PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0004879 nuclear receptor activity | IEA GO_REF:0000107 | REMOVE | Summary: Nuclear receptor activity, propagated from a human IDA annotation (PMID:23610160). Reason: SREBP-1 is a bHLH-ZIP transcription factor activated by regulated proteolysis, not a ligand-activated member of the nuclear hormone receptor superfamily. In the human source paper the nuclear receptor is SF1 (NR5A1), with which SREBP-1 co-occupies a promoter. The term is wrong for this gene, so its ISO and IEA copies are removed; the activity is covered by GO:0001228. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0004879 nuclear receptor activity | ISO GO_REF:0000121 | REMOVE | Summary: Nuclear receptor activity, propagated from a human IDA annotation (PMID:23610160). Reason: SREBP-1 is a bHLH-ZIP transcription factor activated by regulated proteolysis, not a ligand-activated member of the nuclear hormone receptor superfamily. In the human source paper the nuclear receptor is SF1 (NR5A1), with which SREBP-1 co-occupies a promoter. The term is wrong for this gene, so its ISO and IEA copies are removed; the activity is covered by GO:0001228. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SOURCE BAD Human IDA (PMID:23610160) assigns the partner nuclear receptor's activity (SF1) to SREBP-1. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nucleus: the processed N-terminal fragment enters the nucleus to activate transcription. Reason: Location where the core activity is performed; rat studies measure nuclear SREBP-1 (e.g. PMID:16222032, PMID:12421847) and UniProt records the processed form as nuclear. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis PMID:16222032 Insulin treatment of rat primary hepatocytes rapidly augments nSREBP-1 |
| GO:0005654 nucleoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleoplasm (human ISO / IEA). Reason: The nuclear form acts on chromatin in the nucleoplasm; consistent with the nucleus rows and with human data. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleoplasm (human ISO / IEA). Reason: The nuclear form acts on chromatin in the nucleoplasm; consistent with the nucleus rows and with human data. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | MODIFY | Summary: Cytoplasm (mouse ISO, ISS, IEA). Reason: The cytoplasmic pool of SREBP-1 is the membrane-bound precursor in the ER (and Golgi). The specific location, ER membrane, is already on the gene; cytoplasm is correct but general. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasm (mouse ISO, ISS, IEA). Reason: The cytoplasmic pool of SREBP-1 is the membrane-bound precursor in the ER (and Golgi). The specific location, ER membrane, is already on the gene; cytoplasm is correct but general. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse precursor is in the ER membrane; cytoplasm is only general. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | MODIFY | Summary: Cytoplasm (mouse ISO, ISS, IEA). Reason: The cytoplasmic pool of SREBP-1 is the membrane-bound precursor in the ER (and Golgi). The specific location, ER membrane, is already on the gene; cytoplasm is correct but general. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | ACCEPT | Summary: Endoplasmic reticulum (human ISO). Reason: Root organelle term: the claim holds (the precursor is an ER integral membrane protein, PMID:19158095), so the row is kept; the sub-compartment, ER membrane, is carried separately. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endoplasmic reticulum membrane: site of the SCAP-SREBP-1 precursor. Reason: The precursor is embedded in the ER membrane by two transmembrane helices and is retained there by SCAP/INSIG until sterols fall (PMID:19158095 for rat SREBP-1c). The Reactome row describes FOXO1 repression of the rat Srebf1 promoter; the location it attaches is nonetheless correct. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: Endoplasmic reticulum membrane: site of the SCAP-SREBP-1 precursor. Reason: The precursor is embedded in the ER membrane by two transmembrane helices and is retained there by SCAP/INSIG until sterols fall (PMID:19158095 for rat SREBP-1c). The Reactome row describes FOXO1 repression of the rat Srebf1 promoter; the location it attaches is nonetheless correct. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Endoplasmic reticulum membrane: site of the SCAP-SREBP-1 precursor. Reason: The precursor is embedded in the ER membrane by two transmembrane helices and is retained there by SCAP/INSIG until sterols fall (PMID:19158095 for rat SREBP-1c). The Reactome row describes FOXO1 repression of the rat Srebf1 promoter; the location it attaches is nonetheless correct. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-NUL-9625366 | ACCEPT | Summary: Endoplasmic reticulum membrane: site of the SCAP-SREBP-1 precursor. Reason: The precursor is embedded in the ER membrane by two transmembrane helices and is retained there by SCAP/INSIG until sterols fall (PMID:19158095 for rat SREBP-1c). The Reactome row describes FOXO1 repression of the rat Srebf1 promoter; the location it attaches is nonetheless correct. Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of DNA-templated transcription (mouse ISO). Reason: SREBP-1 is an activator of Pol II genes; the positive, Pol II-specific descendant GO:0045944 is already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse donor is sound; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of DNA-templated transcription (mouse ISO). Reason: SREBP-1 is an activator of Pol II genes; the positive, Pol II-specific descendant GO:0045944 is already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse donor is sound; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | MODIFY | Summary: Regulation of transcription by RNA polymerase II. Reason: True but general; SREBP-1 activates Pol II transcription, so MODIFY to GO:0045944, already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107585 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. MGI:MGI:107606 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. PANTHER:PTN002488844 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MODIFY | Summary: Regulation of transcription by RNA polymerase II. Reason: True but general; SREBP-1 activates Pol II transcription, so MODIFY to GO:0045944, already on the gene by IDA. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of transcription by RNA polymerase II. Reason: True but general; SREBP-1 activates Pol II transcription, so MODIFY to GO:0045944, already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of transcription by RNA polymerase II. Reason: True but general; SREBP-1 activates Pol II transcription, so MODIFY to GO:0045944, already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of transcription by RNA polymerase II. Reason: True but general; SREBP-1 activates Pol II transcription, so MODIFY to GO:0045944, already on the gene by IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. UniProtKB:P36956-PRO_0000314029 SUPPORTS TRANSFER SREBP family node regulates Pol II transcription positively; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0007584 response to nutrient | IEP PMID:26394137 Effect of Creosote Bush-Derived NDGA on Expression of Genes ... | KEEP AS NON CORE | Summary: Response to nutrient (IEP): hepatic SREBP-1c mRNA falls with NDGA treatment in high-fructose-fed rats. Reason: Expression of SREBP-1c is strongly nutritionally regulated; the cited study reports reduced SREBP-1c mRNA in diet-challenged rat liver. True as an expression response, peripheral to the TF function. Supporting Evidence: PMID:26394137 decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors) |
| GO:0007623 circadian rhythm | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Circadian rhythm (mouse ISO / IEA). Reason: Rhythmic expression and processing of SREBP-1 follow feeding cycles and the clock; SREBP-1 is an output of the rhythm, not a component that generates it. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP |
| GO:0007623 circadian rhythm | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Circadian rhythm (mouse ISO / IEA). Reason: Rhythmic expression and processing of SREBP-1 follow feeding cycles and the clock; SREBP-1 is an output of the rhythm, not a component that generates it. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse donor reflects rhythmic regulation of SREBP-1, i.e. a clock output. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP |
| GO:0008203 cholesterol metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Cholesterol metabolic process. Reason: SREBP-1 does not catalyse steps of cholesterol metabolism; it activates genes for cholesterol synthesis (mainly SREBP-1a) and uptake. The rat IMP (PMID:18071061, abstract only) shows that SREBP-1 activity controls hepatic cholesterol accumulation, a regulatory role. GO:0045542 is already on the gene. Proposed replacements: positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression |
| GO:0008203 cholesterol metabolic process | IMP PMID:18071061 Identification of mutated Srebf1 as a QTL influencing risk f... | MODIFY | Summary: Cholesterol metabolic process. Reason: SREBP-1 does not catalyse steps of cholesterol metabolism; it activates genes for cholesterol synthesis (mainly SREBP-1a) and uptake. The rat IMP (PMID:18071061, abstract only) shows that SREBP-1 activity controls hepatic cholesterol accumulation, a regulatory role. GO:0045542 is already on the gene. Proposed replacements: positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression |
| GO:0008203 cholesterol metabolic process | ISO GO_REF:0000121 | MODIFY | Summary: Cholesterol metabolic process. Reason: SREBP-1 does not catalyse steps of cholesterol metabolism; it activates genes for cholesterol synthesis (mainly SREBP-1a) and uptake. The rat IMP (PMID:18071061, abstract only) shows that SREBP-1 activity controls hepatic cholesterol accumulation, a regulatory role. GO:0045542 is already on the gene. Propagation Review Root cause: NO FAILURE CORE Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Human donor reflects transcriptional regulation of cholesterol genes. Proposed replacements: positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression |
| GO:0008286 insulin receptor signaling pathway | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Insulin receptor signaling pathway (mouse ISO, acts_upstream_of_or_within). Reason: SREBP-1c is a downstream target of insulin signalling (insulin induces its transcription and processing, PMID:10207099, PMID:19158095), not a component of the receptor pathway. Insulin-responsiveness is captured by the response-to-insulin rows. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype row; SREBP-1c is an effector downstream of insulin signalling. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000120 | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0008610 lipid biosynthetic process | ISO GO_REF:0000121 | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Propagation Review Root cause: NO FAILURE CORE Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Donors describe transcriptional control of lipid synthesis genes. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0008610 lipid biosynthetic process | ISO GO_REF:0000121 | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Propagation Review Root cause: NO FAILURE CORE Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Donors describe transcriptional control of lipid synthesis genes. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0008610 lipid biosynthetic process | ISS GO_REF:0000024 | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0008610 lipid biosynthetic process | ISS GO_REF:0000024 | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0008610 lipid biosynthetic process | TAS PMID:12036955 Ethanol induces fatty acid synthesis pathways by activation ... | MODIFY | Summary: Lipid biosynthetic process. Reason: SREBP-1 is not an enzyme of lipid synthesis; it activates transcription of lipogenic (FAS, ACC, L-PK, S14, SCD1) and cholesterogenic genes. The rat TAS (PMID:12036955) describes ethanol activating SREBP-1 to increase lipogenic gene expression, also a regulatory role. Replace with the positive-regulation terms for fatty acid and cholesterol biosynthesis. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 |
| GO:0009267 cellular response to starvation | IDA PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | KEEP AS NON CORE | Summary: Cellular response to starvation: SREBP-1c and its targets (e.g. PCSK9) fall with fasting and rise on refeeding. Reason: SREBP-1c expression and activity are down-regulated by fasting, which lowers lipogenic and PCSK9 transcription (PMID:16407292, abstract only, curator IDA deferred to). A true nutritional response, peripheral to the core TF activity. Supporting Evidence: PMID:16407292 PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0009267 cellular response to starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to starvation: SREBP-1c and its targets (e.g. PCSK9) fall with fasting and rise on refeeding. Reason: SREBP-1c expression and activity are down-regulated by fasting, which lowers lipogenic and PCSK9 transcription (PMID:16407292, abstract only, curator IDA deferred to). A true nutritional response, peripheral to the core TF activity. Supporting Evidence: PMID:16407292 PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0009267 cellular response to starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to starvation: SREBP-1c and its targets (e.g. PCSK9) fall with fasting and rise on refeeding. Reason: SREBP-1c expression and activity are down-regulated by fasting, which lowers lipogenic and PCSK9 transcription (PMID:16407292, abstract only, curator IDA deferred to). A true nutritional response, peripheral to the core TF activity. Supporting Evidence: PMID:16407292 PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting PMID:16407292 Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:17526932 Sterol regulatory element-binding protein-2- and liver X rec... | KEEP AS NON CORE | Summary: Response to xenobiotic stimulus (IEP, PMID:17526932), statin/compactin study of ABCA1 regulation. Reason: Abstract only; the abstract concerns SREBP-2 and LXR regulation of ABCA1 promoters and does not mention SREBP-1, so the curator's basis in the full text could not be checked. The claim itself is independently supported for rat SREBP-1 by PMID:18171911 (HIV protease inhibitors raise SREBP-1 protein), so the row is kept as non-core, consistent with the other row on this term. Supporting Evidence: PMID:17526932 Compactin activated the novel liver-type promoter in rat hepatoma McARH7777 cells by binding the sterol regulatory element-binding protein-2 (SREBP-2) PMID:18171911 IDV administration resulted in significantly greater SOCS-1, TNF-Ξ±, and SREBP-1 protein expression levels |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18171911 HIV-protease inhibitors induce expression of suppressor of c... | KEEP AS NON CORE | Summary: Response to xenobiotic stimulus (IEP). Reason: Full text of PMID:18171911 read: HIV protease inhibitors (indinavir and others) increased SREBP-1 protein in rat skeletal muscle, liver and L6 myotubes. A true expression response, not a core function. Supporting Evidence: PMID:18171911 IDV administration resulted in significantly greater SOCS-1, TNF-Ξ±, and SREBP-1 protein expression levels |
| GO:0009749 response to glucose | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to glucose (mouse ISO, acts_upstream_of_or_within). Reason: Supported in rat: ADD1/SREBP-1c is required for glucose induction of lipogenic genes in rat hepatocytes (PMID:10207099). A physiological context of the activator function rather than the core function. Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0009750 response to fructose | IEP PMID:11934685 Amelioration of high fructose-induced metabolic derangements... | KEEP AS NON CORE | Summary: Response to fructose (IEP): hepatic SREBP-1 expression rises in high-fructose-fed rats. Reason: True expression response in rat liver and isolated hepatocytes; peripheral to the core function. Supporting Evidence: PMID:11934685 the gene expressions of SREBP-1 and lipogenic enzymes in the liver were increased by high fructose feeding |
| GO:0010867 positive regulation of triglyceride biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of triglyceride biosynthetic process. Reason: SREBP-1c activates fatty acid and glycerolipid synthesis genes, driving triglyceride accumulation (rat ethanol and fructose models). True and closely linked to the lipogenic programme, but the core regulatory output is fatty acid synthesis gene activation; kept as non-core in line with the human SREBF1 review. Supporting Evidence: PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0010867 positive regulation of triglyceride biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of triglyceride biosynthetic process. Reason: SREBP-1c activates fatty acid and glycerolipid synthesis genes, driving triglyceride accumulation (rat ethanol and fructose models). True and closely linked to the lipogenic programme, but the core regulatory output is fatty acid synthesis gene activation; kept as non-core in line with the human SREBF1 review. Supporting Evidence: PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0010867 positive regulation of triglyceride biosynthetic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of triglyceride biosynthetic process. Reason: SREBP-1c activates fatty acid and glycerolipid synthesis genes, driving triglyceride accumulation (rat ethanol and fructose models). True and closely linked to the lipogenic programme, but the core regulatory output is fatty acid synthesis gene activation; kept as non-core in line with the human SREBF1 review. Supporting Evidence: PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0010867 positive regulation of triglyceride biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of triglyceride biosynthetic process. Reason: SREBP-1c activates fatty acid and glycerolipid synthesis genes, driving triglyceride accumulation (rat ethanol and fructose models). True and closely linked to the lipogenic programme, but the core regulatory output is fatty acid synthesis gene activation; kept as non-core in line with the human SREBF1 review. Supporting Evidence: PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0012507 ER to Golgi transport vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ER to Golgi transport vesicle membrane: the SCAP-SREBP complex travels in COPII vesicles. Reason: Shown for rat SREBP-1c: insulin increases association of SCAP-SREBP-1c with COPII proteins and its ER-to-Golgi transport (PMID:19158095). Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0016020 membrane | IEA GO_REF:0000107 | MODIFY | Summary: Membrane (mouse ISO / IEA). Reason: The precursor has two transmembrane helices and resides in the ER membrane, then the Golgi membrane; both specific terms are already on the gene. Proposed replacements: endoplasmic reticulum membrane Golgi membrane Supporting Evidence: UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane UniProtKB:P56720 Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed |
| GO:0016020 membrane | ISO GO_REF:0000121 | MODIFY | Summary: Membrane (mouse ISO / IEA). Reason: The precursor has two transmembrane helices and resides in the ER membrane, then the Golgi membrane; both specific terms are already on the gene. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Membrane is correct; ER and Golgi membrane are the specific sites. Proposed replacements: endoplasmic reticulum membrane Golgi membrane Supporting Evidence: UniProtKB:P56720 Precursor of the transcription factor form (Processed sterol regulatory element- binding protein 1), which is embedded in the endoplasmic reticulum membrane UniProtKB:P56720 Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed |
| GO:0019217 regulation of fatty acid metabolic process | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of fatty acid metabolic process (mouse ISO, acts_upstream_of_or_within). Reason: SREBP-1c positively regulates fatty acid synthesis by activating FAS, ACC and related genes (PMID:10207099); the specific and signed term is GO:0045723. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse donor is sound; term lacks direction and specificity. Proposed replacements: positive regulation of fatty acid biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Protein kinase binding (mouse ISO / IEA). Reason: SREBP-1 is a substrate of several kinases (Akt, AMPK, SIK1, GSK3), which phosphorylate it to regulate processing, activity and turnover. Contact as a kinase substrate is not a binding function of SREBP-1 and adds nothing beyond the PTM record. Supporting Evidence: UniProtKB:P56720 Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression |
| GO:0019901 protein kinase binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Protein kinase binding (mouse ISO / IEA). Reason: SREBP-1 is a substrate of several kinases (Akt, AMPK, SIK1, GSK3), which phosphorylate it to regulate processing, activity and turnover. Contact as a kinase substrate is not a binding function of SREBP-1 and adds nothing beyond the PTM record. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse donor reflects kinase-substrate interaction, not an SREBP-1 binding function. Supporting Evidence: UniProtKB:P56720 Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression |
| GO:0030324 lung development | IEP PMID:12896875 Lipogenesis in fetal rat lung: importance of C/EBPalpha, SRE... | MARK AS OVER ANNOTATED | Summary: Lung development (IEP): SREBP-1c mRNA rises in fetal rat lung on days 19-21. Reason: Abstract only. The evidence is a developmental rise in SREBP-1c mRNA alongside lipogenic enzymes in type II cell maturation; expression timing does not show that SREBP-1 participates in lung development. At most it supports a role in surfactant lipogenesis, captured by the lipogenic regulation terms. Supporting Evidence: PMID:12896875 Regulation of lipogenesis at the mRNA level is predominately on enzymes of fatty acid synthesis and appears to be regulated by C/EBPalpha and SREBP-1c |
| GO:0030522 intracellular receptor signaling pathway | IEA GO_REF:0000108 | REMOVE | Summary: Intracellular receptor signaling pathway, inferred electronically (GO_REF:0000108) from the nuclear receptor activity row. Reason: This row is generated from GO:0004879 nuclear receptor activity, which is itself wrong for SREBP-1 (see that row). SREBP-1 signalling is captured by GO:0032933 SREBP signaling pathway. Supporting Evidence: UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0031647 regulation of protein stability | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of protein stability (human ISO / IEA), from an RNAi screen for Parkin translocation. Reason: The human source (PMID:24912190) found SREBF1 knockdown reduced PINK1 stabilisation, but exogenous lipids bypassed the block, so the effect is through lipid supply, not a function of SREBP-1 on protein stability. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0031647 regulation of protein stability | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of protein stability (human ISO / IEA), from an RNAi screen for Parkin translocation. Reason: The human source (PMID:24912190) found SREBF1 knockdown reduced PINK1 stabilisation, but exogenous lipids bypassed the block, so the effect is through lipid supply, not a function of SREBP-1 on protein stability. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SUPPORTS SOURCE BUT NOT TARGET Human IMP from a genome-wide RNAi screen; indirect lipid-supply effect. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0032094 response to food | IEP PMID:19357831 Role of atypical protein kinase C in activation of sterol re... | KEEP AS NON CORE | Summary: Response to food (IEP), from a rat diabetes study of aPKC-dependent hepatic SREBP-1c activation. Reason: SREBP-1c expression and activation respond to feeding and insulin; the study links hepatic aPKC to SREBP-1c production in Goto-Kakizaki rats. True as a regulatory response, peripheral to the core function. Supporting Evidence: PMID:19357831 Hepatic aPKC may also contribute importantly to excessive SREPB-1c and NFkappaB activities |
| GO:0032526 response to retinoic acid | IEP PMID:9121491 An adipogenic basic helix-loop-helix-leucine zipper type tra... | KEEP AS NON CORE | Summary: Response to retinoic acid (IEP): ADD1 mRNA induced by retinoic acid in rat osteoblastic cells. Reason: Abstract only, but the abstract directly reports dose-dependent induction in ROS17/2.8 cells. A true expression response of peripheral relevance. Supporting Evidence: PMID:9121491 Treatment with retinoic acid (RA) enhanced the ADD1 mRNA expression several fold in these cells within 4 h in a dose-dependent manner |
| GO:0032570 response to progesterone | IEP PMID:11278421 Progesterone stimulates adipocyte determination and differen... | KEEP AS NON CORE | Summary: Response to progesterone (IEP): progesterone induces ADD1/SREBP-1c transcription in rat preadipocytes. Reason: Abstract shows transcriptional induction in rat parametrial preadipocytes; a peripheral hormonal response. Supporting Evidence: PMID:11278421 progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue |
| GO:0032810 sterol response element binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sterol response element binding: SREBP-1 binds SRE-1 (ATCACCCCAC) through an atypical tyrosine in its basic region. Reason: Defining DNA-binding activity of the SREBP family, shown for rat ADD1/SREBP1 (PMID:7739539) and cited by the curated UniProt record. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0032810 sterol response element binding | ISO GO_REF:0000121 | ACCEPT | Summary: Sterol response element binding: SREBP-1 binds SRE-1 (ATCACCCCAC) through an atypical tyrosine in its basic region. Reason: Defining DNA-binding activity of the SREBP family, shown for rat ADD1/SREBP1 (PMID:7739539) and cited by the curated UniProt record. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0032810 sterol response element binding | ISS PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | ACCEPT | Summary: Sterol response element binding: SREBP-1 binds SRE-1 (ATCACCCCAC) through an atypical tyrosine in its basic region. Reason: Defining DNA-binding activity of the SREBP family, shown for rat ADD1/SREBP1 (PMID:7739539) and cited by the curated UniProt record. Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0032868 response to insulin | TAS PMID:11090130 Regulation of mouse sterol regulatory element-binding protei... | KEEP AS NON CORE | Summary: Response to insulin (TAS). Reason: Insulin induces SREBP-1c transcription and processing (rat hepatocytes, PMID:10207099, PMID:19158095); the cited mouse paper (PMID:11090130) shows LXR-dependent induction. A regulatory input to SREBP-1c, peripheral to its core TF activity. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP PMID:11090130 SREBP-1c expression was markedly increased in mouse tissues in an LXR-dependent manner |
| GO:0032869 cellular response to insulin stimulus | IEP PMID:10207099 ADD1/SREBP-1c is required in the activation of hepatic lipog... | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (IEP): insulin induces SREBP-1c transcription and processing in rat hepatocytes. Reason: Well established in rat hepatocytes (PMID:10207099 transcription; PMID:19158095, full text, processing via Akt-dependent phosphorylation; PMID:24458133 via LXR and Sp1). Kept as non-core: the response is a regulatory input to SREBP-1c rather than its function. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins PMID:24458133 Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1) |
| GO:0032869 cellular response to insulin stimulus | IEP PMID:19158095 Insulin enhances post-translational processing of nascent SR... | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (IEP): insulin induces SREBP-1c transcription and processing in rat hepatocytes. Reason: Well established in rat hepatocytes (PMID:10207099 transcription; PMID:19158095, full text, processing via Akt-dependent phosphorylation; PMID:24458133 via LXR and Sp1). Kept as non-core: the response is a regulatory input to SREBP-1c rather than its function. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins PMID:24458133 Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1) |
| GO:0032869 cellular response to insulin stimulus | IEP PMID:24458133 Cilostazol inhibits insulin-stimulated expression of sterol ... | KEEP AS NON CORE | Summary: Cellular response to insulin stimulus (IEP): insulin induces SREBP-1c transcription and processing in rat hepatocytes. Reason: Well established in rat hepatocytes (PMID:10207099 transcription; PMID:19158095, full text, processing via Akt-dependent phosphorylation; PMID:24458133 via LXR and Sp1). Kept as non-core: the response is a regulatory input to SREBP-1c rather than its function. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins PMID:24458133 Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1) |
| GO:0032933 SREBP signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: SREBP signaling pathway. Reason: SREBP-1 is the defining effector of the pathway: SCAP-dependent ER-to-Golgi transport, S1P/S2P cleavage and nuclear activation of target genes, shown for rat SREBP-1c (PMID:19158095). Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0032933 SREBP signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: SREBP signaling pathway. Reason: SREBP-1 is the defining effector of the pathway: SCAP-dependent ER-to-Golgi transport, S1P/S2P cleavage and nuclear activation of target genes, shown for rat SREBP-1c (PMID:19158095). Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0032933 SREBP signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: SREBP signaling pathway. Reason: SREBP-1 is the defining effector of the pathway: SCAP-dependent ER-to-Golgi transport, S1P/S2P cleavage and nuclear activation of target genes, shown for rat SREBP-1c (PMID:19158095). Supporting Evidence: PMID:19158095 Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c UniProtKB:P56720 translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:0032936 SREBP-SCAP complex | IEA GO_REF:0000107 | ACCEPT | Summary: SREBP-SCAP complex. Reason: The precursor forms a tight complex with SCAP; the SCAP-SREBP-1c complex was pulled down from rat hepatocyte microsomes (PMID:19158095). Supporting Evidence: UniProtKB:P56720 Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane and the Golgi apparatus PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0032936 SREBP-SCAP complex | ISO GO_REF:0000121 | ACCEPT | Summary: SREBP-SCAP complex. Reason: The precursor forms a tight complex with SCAP; the SCAP-SREBP-1c complex was pulled down from rat hepatocyte microsomes (PMID:19158095). Supporting Evidence: UniProtKB:P56720 Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane and the Golgi apparatus PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0032991 protein-containing complex | IDA PMID:19158095 Insulin enhances post-translational processing of nascent SR... | MODIFY | Summary: Protein-containing complex (IDA, PMID:19158095). Reason: Full text read: the complex studied is the SCAP-SREBP-1c complex, for which a specific term exists and is already on the gene. Proposed replacements: SREBP-SCAP complex Supporting Evidence: PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0033762 response to glucagon | IEP PMID:10207099 ADD1/SREBP-1c is required in the activation of hepatic lipog... | KEEP AS NON CORE | Summary: Response to glucagon (IEP): glucagon represses SREBP-1c transcription in rat hepatocytes. Reason: Directly reported in rat hepatocytes (PMID:10207099, full text available). Peripheral regulatory response. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP |
| GO:0033993 response to lipid | IEP PMID:12421847 Dietary polyunsaturated fats regulate rat liver sterol regul... | KEEP AS NON CORE | Summary: Response to lipid (IEP): dietary PUFA suppress proteolytic release of SREBP-1 in rat liver. Reason: Abstract shows that fish-oil PUFA lowered nuclear SREBP-1 without lowering the precursor; a true regulatory response, peripheral. Supporting Evidence: PMID:12421847 These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2 |
| GO:0042789 mRNA transcription by RNA polymerase II | ISO GO_REF:0000121 | MODIFY | Summary: mRNA transcription by RNA polymerase II (mouse ISO, acts_upstream_of_or_within). Reason: SREBP-1 does not take part in the transcription machinery itself; it activates transcription of target genes. The regulatory term GO:0045944 describes its role. Propagation Review Root cause: NO FAILURE CORE Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse phenotype row places a regulator in the transcription process itself. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0043434 response to peptide hormone | IEP PMID:18801905 Central leptin regulates total ceramide content and sterol r... | KEEP AS NON CORE | Summary: Response to peptide hormone (IEP): central leptin impairs SREBP-1c maturation in rat white adipose tissue. Reason: Abstract reports leptin-dependent reduction of SREBP-1c activation via the autonomic nervous system; true but peripheral. Supporting Evidence: PMID:18801905 central leptin treatment markedly increased INSIG-1 mRNA expression and impaired SREBP-1c activation in epididymal WAT |
| GO:0043565 sequence-specific DNA binding | IDA PMID:9786926 Obesity-related overexpression of fatty-acid synthase gene i... | MODIFY | Summary: Sequence-specific DNA binding. Reason: True but general. The rat IDA (PMID:9786926, abstract only) shows ADD1/SREBP1 binding to the sterol regulatory element of the FAS promoter in vitro; together with PMID:7739539 this supports GO:0000978 (and the SRE-specific GO:0032810), which the gene already carries. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:9786926 SREBP2 was able to displace ADD1/SREBP1 binding from the sterol regulatory element (SRE) site PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Sequence-specific DNA binding. Reason: True but general. The rat IDA (PMID:9786926, abstract only) shows ADD1/SREBP1 binding to the sterol regulatory element of the FAS promoter in vitro; together with PMID:7739539 this supports GO:0000978 (and the SRE-specific GO:0032810), which the gene already carries. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:9786926 SREBP2 was able to displace ADD1/SREBP1 binding from the sterol regulatory element (SRE) site PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0043565 sequence-specific DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: Sequence-specific DNA binding. Reason: True but general. The rat IDA (PMID:9786926, abstract only) shows ADD1/SREBP1 binding to the sterol regulatory element of the FAS promoter in vitro; together with PMID:7739539 this supports GO:0000978 (and the SRE-specific GO:0032810), which the gene already carries. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse SREBP-1 sequence-specific binding is established; the term is only general. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:9786926 SREBP2 was able to displace ADD1/SREBP1 binding from the sterol regulatory element (SRE) site PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) |
| GO:0044877 protein-containing complex binding | IPI PMID:19158095 Insulin enhances post-translational processing of nascent SR... | KEEP AS NON CORE | Summary: Protein-containing complex binding: SREBP-1c (with SCAP) binds the Sar1-Sec23/24 COPII complex in rat hepatocyte microsomes, enhanced by insulin. Reason: Full text read. The pull-down shows SREBP-1c and SCAP binding the Sec23/24 complex; SCAP is the escort that carries the MELADL sorting signal, so SREBP-1c is COPII cargo here. The binding is real and regulated by insulin, but it is part of the transport step that precedes activation, not the core transcriptional function. Supporting Evidence: PMID:19158095 we observed a marked increase in SCAP and SREBP-1c binding to the Sar1-Sec23/24 complex in microsomes derived from insulin-treated hepatocytes PMID:19158095 insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins |
| GO:0045089 positive regulation of innate immune response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of innate immune response (mouse ISO), from SREBP-1a function in macrophages. Reason: UniProt records that isoform SREBP-1a is required for the innate immune response in macrophages by regulating lipid metabolism (by similarity to mouse). Plausible and isoform-specific, peripheral to the lipogenic core. Supporting Evidence: UniProtKB:P56720 Required for innate immune response in macrophages by regulating lipid metabolism |
| GO:0045444 fat cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Fat cell differentiation (mouse ISO, acts_upstream_of_or_within). Reason: ADD1 was identified as a factor regulated during adipocyte determination and differentiation, and promotes adipogenic gene expression; a developmental role downstream of its TF activity. Supporting Evidence: PMID:8336713 These data suggest that ADD1 plays a role in the regulation of determination- and differentiation-specific gene expression in adipocytes |
| GO:0045471 response to ethanol | IEP PMID:27939985 Dihydroartemisinin protects against alcoholic liver injury t... | KEEP AS NON CORE | Summary: Response to ethanol (IEP). Reason: The cited abstract (PMID:27939985) does not mention SREBP-1 (full text unavailable), but ethanol activation of SREBP-1 in rat hepatoma cells is shown independently (PMID:12036955) and is the basis of alcoholic steatosis models. Deferring to the curator; non-core. Supporting Evidence: PMID:12036955 ethanol induced transcription of a sterol regulatory element-binding protein (SREBP)-regulated promoter via increased levels of mature SREBP-1 protein |
| GO:0045542 positive regulation of cholesterol biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of cholesterol biosynthetic process. Reason: SREBP-1 (mainly SREBP-1a) activates cholesterogenic genes through SREs; rat genetics shows SREBP-1 activity controls hepatic cholesterol (PMID:18071061). Supporting Evidence: UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cholesterol biosynthetic process. Reason: SREBP-1 (mainly SREBP-1a) activates cholesterogenic genes through SREs; rat genetics shows SREBP-1 activity controls hepatic cholesterol (PMID:18071061). Supporting Evidence: UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cholesterol biosynthetic process. Reason: SREBP-1 (mainly SREBP-1a) activates cholesterogenic genes through SREs; rat genetics shows SREBP-1 activity controls hepatic cholesterol (PMID:18071061). Supporting Evidence: UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cholesterol biosynthetic process. Reason: SREBP-1 (mainly SREBP-1a) activates cholesterogenic genes through SREs; rat genetics shows SREBP-1 activity controls hepatic cholesterol (PMID:18071061). Supporting Evidence: UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0045542 positive regulation of cholesterol biosynthetic process | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of cholesterol biosynthetic process. Reason: SREBP-1 (mainly SREBP-1a) activates cholesterogenic genes through SREs; rat genetics shows SREBP-1 activity controls hepatic cholesterol (PMID:18071061). Supporting Evidence: UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression PMID:18071061 Genetic correction of reduced SREBP-1 activity by derivation of congenic and transgenic strains of SHR increased hepatic cholesterol levels UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | MODIFY | Summary: Positive regulation of DNA-templated transcription. Reason: True; the rat IMP (PMID:10207099) shows that dominant-negative ADD1/SREBP-1c abolishes glucose induction of lipogenic genes. These are Pol II genes, so the Pol II-specific child GO:0045944 is the refinement. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:10207099 ADD1/SREBP-1c is required in the activation of hepatic lipog... | MODIFY | Summary: Positive regulation of DNA-templated transcription. Reason: True; the rat IMP (PMID:10207099) shows that dominant-negative ADD1/SREBP-1c abolishes glucose induction of lipogenic genes. These are Pol II genes, so the Pol II-specific child GO:0045944 is the refinement. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | MODIFY | Summary: Positive regulation of DNA-templated transcription. Reason: True; the rat IMP (PMID:10207099) shows that dominant-negative ADD1/SREBP-1c abolishes glucose induction of lipogenic genes. These are Pol II genes, so the Pol II-specific child GO:0045944 is the refinement. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Donor is sound; term is only general. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16407292 Hepatic PCSK9 expression is regulated by nutritional status ... | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Direct consequence of the activator activity: rat SREBP-1 activates SRE- and E-box-driven promoters (PMID:7739539, PMID:8336713) and drives PCSK9 and lipogenic genes (PMID:16407292, PMID:10207099). Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Direct consequence of the activator activity: rat SREBP-1 activates SRE- and E-box-driven promoters (PMID:7739539, PMID:8336713) and drives PCSK9 and lipogenic genes (PMID:16407292, PMID:10207099). Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Direct consequence of the activator activity: rat SREBP-1 activates SRE- and E-box-driven promoters (PMID:7739539, PMID:8336713) and drives PCSK9 and lipogenic genes (PMID:16407292, PMID:10207099). Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Direct consequence of the activator activity: rat SREBP-1 activates SRE- and E-box-driven promoters (PMID:7739539, PMID:8336713) and drives PCSK9 and lipogenic genes (PMID:16407292, PMID:10207099). Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Direct consequence of the activator activity: rat SREBP-1 activates SRE- and E-box-driven promoters (PMID:7739539, PMID:8336713) and drives PCSK9 and lipogenic genes (PMID:16407292, PMID:10207099). Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression |
| GO:0046676 negative regulation of insulin secretion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of insulin secretion (mouse ISO, acts_upstream_of_or_within). Reason: Based on mouse beta-cell overexpression phenotypes, where excess SREBP-1c lipogenesis causes lipotoxic impairment of secretion. This is an indirect, pathological consequence, not a regulatory function of SREBP-1. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype from transgenic beta-cell overexpression; indirect lipotoxic effect. Supporting Evidence: UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0046889 positive regulation of lipid biosynthetic process | ISO GO_REF:0000121 | MODIFY | Summary: Positive regulation of lipid biosynthetic process (mouse ISO). Reason: Correct but general; the specific processes SREBP-1 activates are fatty acid and cholesterol biosynthesis, so MODIFY to those descendants. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107606 SUPPORTS TRANSFER Mouse donor is sound; term is only general. Proposed replacements: positive regulation of fatty acid biosynthetic process positive regulation of cholesterol biosynthetic process Supporting Evidence: PMID:10207099 we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression PMID:11090130 Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis UniProtKB:P56720 Able to stimulate both lipogenic and cholesterogenic gene expression |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Protein dimerization activity, from the bHLH InterPro signatures. Reason: bHLH-ZIP proteins bind DNA as dimers and UniProt records that efficient DNA binding requires dimerization with another bHLH protein. The term is true but subsidiary to the DNA-binding activator function. Supporting Evidence: UniProtKB:P56720 Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein UniProtKB:P56720 bHLH |
| GO:0050796 regulation of insulin secretion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of insulin secretion (mouse ISO, acts_upstream_of_or_within). Reason: Based on mouse beta-cell overexpression phenotypes, where excess SREBP-1c lipogenesis causes lipotoxic impairment of secretion. This is an indirect, pathological consequence, not a regulatory function of SREBP-1. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:107606 SUPPORTS SOURCE BUT NOT TARGET Mouse phenotype from transgenic beta-cell overexpression; indirect lipotoxic effect. Supporting Evidence: UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:0051591 response to cAMP | IEP PMID:10207099 ADD1/SREBP-1c is required in the activation of hepatic lipog... | KEEP AS NON CORE | Summary: Response to cAMP (IEP): cAMP represses SREBP-1c transcription in rat hepatocytes. Reason: Directly reported in rat hepatocytes (PMID:10207099, full text available). Peripheral regulatory response. Supporting Evidence: PMID:10207099 the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP |
| GO:0070542 response to fatty acid | IEP PMID:16222032 Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SRE... | KEEP AS NON CORE | Summary: Response to fatty acid (IEP): DHA lowers nuclear SREBP-1 in rat hepatocytes. Reason: Abstract reports 22:6 n-3 suppression of nuclear SREBP-1 and SREBP-1c mRNA via Erk and the proteasome; a true, peripheral regulatory response. Supporting Evidence: PMID:16222032 22:6,n-3, the major n-3 PUFA accumulating in livers of fish oil-fed rats, suppresses hepatocyte levels of nSREBP-1, mRNA(SREBP-1c), and mRNA(Insig-2) |
| GO:0071398 cellular response to fatty acid | IEP PMID:19332540 Palmitate induces insulin resistance in H4IIEC3 hepatocytes ... | KEEP AS NON CORE | Summary: Cellular response to fatty acid (IEP): palmitate down-regulates SREBP-1c expression in H4IIEC3 hepatoma cells. Reason: Full text read. SREBP-1c is peripheral in this paper, which concludes that palmitate insulin resistance does not act through SREBP-1c, but it does show SREBP-1c mRNA falling with palmitate, likely as feedback on fatty acid synthesis. True expression response. Supporting Evidence: PMID:19332540 palmitate dramatically down-regulated the expression of SREBP-1c in H4IIEC3 hepatocytes |
| GO:0090209 negative regulation of triglyceride metabolic process | ISO GO_REF:0000121 | MODIFY | Summary: Negative regulation of triglyceride metabolic process (human ISO, acts_upstream_of). Reason: Sign correction. In the human source (PMID:28483554) SREBF1 up-regulation drives lipogenesis and steatosis and miR-192 relieves steatosis by suppressing SREBF1; the negative regulation belongs to the miRNA, not to SREBP-1. SREBP-1 promotes triglyceride synthesis (GO:0010867, already on the gene). Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:P36956 SOURCE BAD Human IDA (PMID:28483554) attributes the miRNA's negative effect to SREBF1. Proposed replacements: positive regulation of triglyceride biosynthetic process Supporting Evidence: PMID:12036955 metabolism of ethanol increased hepatic lipogenesis by activating SREBP-1 UniProtKB:P56720 Primarily controls expression of lipogenic gene |
| GO:1901524 regulation of mitophagy | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of mitophagy (human ISO / IEA), from an RNAi screen for Parkin translocation. Reason: In the human source (PMID:24912190) SREBF1 knockdown impaired Parkin translocation and mitophagy, but exogenous lipids bypassed the block. SREBP-1 affects mitophagy indirectly through lipid synthesis. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:1901524 regulation of mitophagy | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of mitophagy (human ISO / IEA), from an RNAi screen for Parkin translocation. Reason: In the human source (PMID:24912190) SREBF1 knockdown impaired Parkin translocation and mitophagy, but exogenous lipids bypassed the block. SREBP-1 affects mitophagy indirectly through lipid synthesis. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SUPPORTS SOURCE BUT NOT TARGET Human IMP from a genome-wide RNAi screen; indirect lipid-supply effect. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:1902895 positive regulation of miRNA transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of miRNA transcription (human ISO / IEA). Reason: SREBP-1 activates some miRNA host genes (human data); a target-specific outcome of its Pol II activator function, peripheral to the core lipogenic programme. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of miRNA transcription (human ISO / IEA). Reason: SREBP-1 activates some miRNA host genes (human data); a target-specific outcome of its Pol II activator function, peripheral to the core lipogenic programme. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of miRNA transcription (human ISO / IEA). Reason: SREBP-1 activates some miRNA host genes (human data); a target-specific outcome of its Pol II activator function, peripheral to the core lipogenic programme. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of miRNA transcription (human ISO / IEA). Reason: SREBP-1 activates some miRNA host genes (human data); a target-specific outcome of its Pol II activator function, peripheral to the core lipogenic programme. Supporting Evidence: PMID:7739539 When expressed in fibroblasts, ADD1/SREBP1 activates transcription through both the carbohydrate response E-box element and SRE-1 |
| GO:1903747 obsolete regulation of protein localization to mitochondrion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Obsolete regulation of protein localization to mitochondrion (human ISO / IEA). Reason: Same RNAi-screen source (PMID:24912190) as the mitophagy row; the effect on Parkin recruitment is indirect, through lipid supply. The term is also obsolete in GO. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:1903747 obsolete regulation of protein localization to mitochondrion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Obsolete regulation of protein localization to mitochondrion (human ISO / IEA). Reason: Same RNAi-screen source (PMID:24912190) as the mitophagy row; the effect on Parkin recruitment is indirect, through lipid supply. The term is also obsolete in GO. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P36956 SUPPORTS SOURCE BUT NOT TARGET Human IMP from a genome-wide RNAi screen; indirect lipid-supply effect. Supporting Evidence: UniProtKB:P56720 Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Sequence-specific double-stranded DNA binding. Reason: True but general; the bound sequences are SRE-1 and E-box elements in Pol II promoters, so MODIFY to GO:0000978, already on the gene by IBA and IDA. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
| GO:1990837 sequence-specific double-stranded DNA binding | ISO GO_REF:0000121 | MODIFY | Summary: Sequence-specific double-stranded DNA binding. Reason: True but general; the bound sequences are SRE-1 and E-box elements in Pol II promoters, so MODIFY to GO:0000978, already on the gene by IBA and IDA. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P36956 SUPPORTS TRANSFER Human SREBP-1 binds SRE dsDNA; the term is only general. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:7739539 we demonstrate that ADD1/SREBP1 has dual DNA sequence specificity, binding to both an E-box motif (ATCACGTGA) and a non-E-box sequence previously shown to be important in cholesterol metabolism, sterol regulatory element 1 (SRE-1; ATCACCCCAC) UniProtKB:P56720 Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') PMID:16407292 verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG |
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Download this section (compressed HTML)Q: Should rat Srebf1 carry GO:0070888 E-box binding (PMID:7739539) in addition to sterol response element binding, given that SREBP-1c activates lipogenic promoters through carbohydrate-response E-boxes?
Q: Does the human IDA to nuclear receptor activity (PMID:23610160) reflect SREBP-1 activity at all, or should it be repointed to DNA-binding transcription activator activity?
Q: Which rat lipogenic promoters are activated through SRE-1 versus E-box elements in vivo, and does the SREBP-1c isoform use the E-box mode preferentially?
Experiment: ChIP-seq of nuclear SREBP-1 in refed rat liver with motif analysis, and reporter assays with the tyrosine-to-arginine basic-region mutant, to quantify SRE-1 versus E-box occupancy at lipogenic targets.
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