CREB1 (Cyclic AMP-responsive element-binding protein 1) is a nuclear bZIP transcription factor that binds as homo- or heterodimers to cAMP response elements (CRE; palindromic sequence TGACGTCA) in target gene promoters. The protein contains an N-terminal transactivation domain (with Q1-KID-Q2 regions) and a C-terminal basic leucine zipper (bZIP) domain for DNA binding and dimerization. Phosphorylation of Ser-119 (Ser-133 in some numbering) by upstream kinases (PKA, CaMKs, AKT, RSKs, MSKs) promotes recruitment of coactivators CBP/p300 via the KID-KIX interaction, activating transcription. CRTC coactivators can also enhance CREB-dependent transcription independently of Ser-119 phosphorylation. CREB1 mediates cAMP-responsive gene expression in response to diverse stimuli including hormones, growth factors, and neuronal activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: CREB1 is a well-established bZIP transcription factor that binds DNA as dimers and activates RNA polymerase II-dependent transcription. This is a core molecular function supported by extensive literature including structural studies of the bZIP domain and functional studies of CRE-dependent transcription (Belgacem & Borodinsky 2017, Steven et al. 2020). Reason: Core molecular function. CREB1 contains a bZIP domain (IPR004827) and KID domain (IPR003102) characteristic of this transcription factor family. IBA annotation is well-supported by phylogenetic conservation across eukaryotes. Supporting Evidence: PMID:1655749 ATF-1, like CREB, is expressed in a wide variety of cell types, and ATF-1 is capable of dimerizing with CREB. Both ATF-1 homodimers and ATF-1/CREB heterodimers bind to the CRE file:human/CREB1/CREB1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: CREB1 regulates transcription by RNA polymerase II through binding to CRE elements and recruiting coactivators. This is a core biological process annotation directly related to its molecular function as a transcription factor. Reason: Core biological process. CREB1 directly regulates Pol II-dependent transcription by binding CRE sites and recruiting CBP/p300 coactivators upon phosphorylation. Supporting Evidence: PMID:11522779 transcription of a PEPCK chloramphenicol acetyltransferase (CAT) reporter gene activated by protein kinase A (PKA) is enhanced 7-fold by SRCAP |
| GO:0141156 cAMP/PKA signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: CREB1 is a central effector of cAMP/PKA signaling. PKA phosphorylates CREB1 at Ser-119, enabling recruitment of CBP/p300 and transcriptional activation of cAMP-responsive genes. This is a defining feature of CREB1 function. Reason: Core function - CREB1 is literally named for its role as a cAMP-responsive element binding protein. The KID domain contains the PKA phosphorylation site (Ser-119) that is essential for signal-dependent activation. Supporting Evidence: PMID:11522779 SRCAP functions as a coactivator for PKA-activated factors such as CREB PMID:1655749 ATF-1 is as active as CREB in its ability to mediate the transcriptional effects of PKA |
| GO:0035497 cAMP response element binding | IBA GO_REF:0000033 | ACCEPT | Summary: CRE binding is the defining molecular function of CREB1. The protein binds the palindromic CRE sequence (TGACGTCA) as dimers via its bZIP domain. This is the core DNA binding specificity of CREB1. Reason: Core molecular function. CRE binding is what distinguishes CREB family members from other bZIP transcription factors. Well-supported by structural and biochemical studies. Supporting Evidence: PMID:19861239 Using chromatin immunoprecipitation assays we showed comparable in vivo cJun and CREB1 binding to the G-CRE region PMID:8798441 Electrophoretic mobility shift assays with the bcl-2 CRE demonstrated complexes with mobilities identical to those with a consensus CRE |
| GO:1990589 ATF4-CREB1 transcription factor complex | IBA GO_REF:0000033 | ACCEPT | Summary: CREB1 forms heterodimeric complexes with ATF4, particularly in the context of ER stress response. The ATF4-CREB1 complex activates genes like GRP78/BiP through ATF/CRE sites (PMID:12871976). Reason: Valid cellular component annotation. CREB1 can heterodimerize with other bZIP factors including ATF4, ATF1, and CREM through its leucine zipper domain. Supporting Evidence: PMID:12871976 we have identified the closely related ATF1 and CREB1 as nuclear co-factors that form in vivo complexes with endogenous ATF4 |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 binds DNA via its bZIP domain. While accurate, this is a parent term of the more specific GO:0035497 (cAMP response element binding) which better describes CREB1's DNA binding specificity. Reason: Accurate but less informative than GO:0035497. The IEA annotation based on domain (bZIP) is correct. Keep as it provides broader context alongside the more specific CRE binding annotation. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 is a DNA-binding transcription factor. This is a parent term of the more specific GO:0000981 (RNA polymerase II-specific) annotation. Reason: Accurate general annotation. The more specific child term GO:0000981 is also present and provides better specificity. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 is a nuclear transcription factor. Nuclear localization is required for its function and is enhanced by sumoylation at Lys-290 (UniProt). Reason: Core cellular component. CREB1 functions in the nucleus to regulate transcription. Well-supported by multiple experimental studies. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: CREB1 regulates DNA-templated transcription. This is a parent term of more specific process annotations already present. Reason: Accurate general annotation inferred from InterPro domains. More specific annotations (GO:0006357, GO:0045944) provide better detail. |
| GO:0030154 cell differentiation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CREB1 plays roles in differentiation of various cell types including adipocytes and neurons, as a downstream effector of differentiation signals that activate cAMP/PKA pathways. Reason: CREB1 participates in differentiation but this is a downstream consequence of its transcriptional activity rather than a core function. It regulates differentiation genes in response to upstream signals. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This IEA annotation is based on the UniProt keyword "Biological rhythms". While CREB1 can regulate some clock gene expression and phosphorylation of Ser-119 and Ser-128 in the suprachiasmatic nucleus (SCN) participates in circadian rhythm generation, rhythmic process is NOT a core function of CREB1. The deep research review covers neuronal activity-dependent transcription, metabolic regulation, cancer, and immune function without emphasis on circadian rhythms. Reason: CREB1's core function is cAMP-responsive transcription. While it may regulate some clock genes, this is context-dependent and not a defining function. The annotation appears to derive from studies showing CREB involvement in SCN signaling, but rhythm regulation is downstream of its core transcription factor activity. |
| GO:0005515 protein binding | IPI PMID:10722738 cAMP-independent activation of the adenovirus type 12 E2 pro... | REMOVE | Summary: Generic protein binding annotation from interaction with adenovirus E1A protein. This uninformative term should be replaced with more specific binding terms. Reason: GO:0005515 (protein binding) is uninformative per GO curation guidelines. CREB1 has multiple specific binding partners (CBP/p300, CRTCs, other bZIP factors) that are better captured by more specific terms. Supporting Evidence: PMID:10722738 cAMP-independent activation of the adenovirus type 12 E2 promoter correlates with the recruitment of CREB-1/ATF-1, E1A(12S), and CBP to the E2-CRE. |
| GO:0005515 protein binding | IPI PMID:15733869 Serum/glucocorticoid-inducible kinase can phosphorylate the ... | REMOVE | Summary: Generic protein binding from interaction with SGK1 kinase. SGK1 phosphorylates CREB1 at Ser-119. Reason: Uninformative generic term. The interaction with SGK1 is a kinase-substrate relationship, not a generic binding interaction. Supporting Evidence: PMID:15733869 Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic AMP response element binding protein, CREB. |
| GO:0005515 protein binding | IPI PMID:15964553 TSSK5, a novel member of the testis-specific serine/threonin... | REMOVE | Summary: Generic protein binding from interaction with TSSK4 kinase. TSSK4 phosphorylates CREB1 at Ser-119. Reason: Uninformative generic term. This is a kinase-substrate relationship. Supporting Evidence: PMID:15964553 TSSK5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates CREB at Ser-133, and stimulates the CRE/CREB responsive pathway. |
| GO:0005515 protein binding | IPI PMID:16799563 An ARC/Mediator subunit required for SREBP control of choles... | REMOVE | Summary: Generic protein binding from interaction with CREBBP (CBP). This is a functionally important interaction - phosphorylated CREB1 recruits CBP via KID-KIX interaction. Reason: Uninformative generic term. The CREB1-CBP interaction is better captured by more specific terms like GO:0001223 (transcription coactivator binding). Supporting Evidence: PMID:16799563 An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. |
| GO:0005515 protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | REMOVE | Summary: Generic protein binding from coiled-coil array study identifying bZIP interaction partners. Identified interactions with viral proteins HBZ, MEQ and cellular bZIP factors ATF1, NFIL3. Reason: Uninformative generic term. The specific interactions with other bZIP factors are better captured by GO:0042802 (identical protein binding) for homodimerization or specific heterodimer annotations. Supporting Evidence: PMID:20102225 Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays. |
| GO:0005515 protein binding | IPI PMID:20159610 PML/RARalpha targets promoter regions containing PU.1 consen... | REMOVE | Summary: Generic protein binding from interaction with MEIS1. Reason: Uninformative generic term per GO curation guidelines. Supporting Evidence: PMID:20159610 PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia. |
| GO:0005515 protein binding | IPI PMID:20541704 GSK-3 promotes conditional association of CREB and its coact... | REMOVE | Summary: Generic protein binding from study showing GSK-3 promotes CREB association with MEIS1 for HOX-mediated transcription. Reason: Uninformative generic term. The biological context (transcriptional co-regulation) is better captured by other annotations. Supporting Evidence: PMID:20541704 GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: Generic protein binding from MAP kinase interactome study with CRTC1. Reason: Uninformative generic term. CRTC1 is a CREB coactivator - this functional relationship is better represented by specific annotations. Supporting Evidence: PMID:20936779 A human MAP kinase interactome. |
| GO:0005515 protein binding | IPI PMID:21418524 Substrate preference and phosphatidylinositol monophosphate ... | REMOVE | Summary: Generic protein binding from study with PASKIN (PASK) kinase. Reason: Uninformative generic term. Supporting Evidence: PMID:21418524 2011 Apr 8. Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Generic protein binding from liver protein interactome study with TSSK4. Reason: Uninformative generic term. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | REMOVE | Summary: Generic protein binding from chromatin-associated transcription factor complex study. Reason: Uninformative generic term. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from human binary protein interactome reference map. Reason: Uninformative generic term from high-throughput study. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Generic protein binding from neurodegenerative disease protein interactome study showing interaction with HTT (huntingtin). Reason: Uninformative generic term. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0042802 identical protein binding | IPI PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: CREB1 homodimerization via the leucine zipper domain. CREB1 functions as homodimers or heterodimers when binding DNA. Reason: Valid molecular function. Dimerization via the leucine zipper is essential for DNA binding and transcriptional activity. More informative than generic protein binding. Supporting Evidence: PMID:1655749 ATF-1 is capable of dimerizing with CREB. Both ATF-1 homodimers and ATF-1/CREB heterodimers bind to the CRE PMID:20102225 Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays. |
| GO:0042802 identical protein binding | IPI PMID:23661758 Networks of bZIP protein-protein interactions diversified ov... | ACCEPT | Summary: CREB1 homodimerization from bZIP protein-protein interaction network study. Reason: Valid molecular function annotation for homodimerization. Supporting Evidence: PMID:23661758 Networks of bZIP protein-protein interactions diversified over a billion years of evolution. |
| GO:0042802 identical protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | ACCEPT | Summary: CREB1 homodimerization from chromatin-associated transcription factor complex study. Reason: Valid molecular function annotation for homodimerization. Supporting Evidence: PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. |
| GO:0000785 chromatin | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 associates with chromatin at CRE-containing promoters and enhancers. Supported by ChIP studies showing CREB1 occupancy at target gene promoters. Reason: Valid cellular component. CREB1 binds chromatin at CRE sites to regulate transcription. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 binds cis-regulatory regions containing CRE elements. This is a parent term of the more specific CRE binding annotation. Reason: Accurate general annotation. More specific term GO:0035497 (cAMP response element binding) provides better detail. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 binds sequence-specifically to CRE elements in Pol II-transcribed gene promoters. Reason: Core molecular function describing CREB1's DNA binding specificity at Pol II promoters. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of IBA annotation. CREB1 is a Pol II-specific transcription factor. Reason: Core molecular function. IEA annotation consistent with IBA annotation. |
| GO:0001223 transcription coactivator binding | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 binds transcriptional coactivators CBP/p300 and CRTCs. The KID-KIX interaction between phosphorylated CREB1 and CBP/p300 is essential for transcriptional activation. Reason: Core molecular function. Coactivator recruitment is essential for CREB1-mediated transcription. Supporting Evidence: PMID:11522779 SRCAP binds to CBP amino acids 280-460, a region that is important for CBP to function as a coactivator for CREB |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 functions primarily as a transcriptional activator when phosphorylated. Upon Ser-119 phosphorylation, it recruits CBP/p300 to activate target gene transcription. Reason: Core molecular function. CREB1 is an activator of transcription in response to cAMP signaling. |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 responds to hypoxia through sumoylation and other regulatory mechanisms. Hypoxia enhances CREB1 sumoylation, promoting nuclear localization and stabilization (UniProt, PMID:12552083). Reason: Valid biological process but context-dependent rather than core function. CREB1 is regulated by hypoxia but hypoxia response is not its primary role. |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 participates in transcription regulatory complexes with coactivators (CBP/p300, CRTCs) and can form heterodimers with other bZIP factors. Reason: Valid cellular component. CREB1 functions within multiprotein transcriptional complexes. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000107 | UNDECIDED | Summary: Some studies suggest CREB1 may have mitochondrial functions, but this is not well-established for the nuclear transcription factor. CREB1 primarily functions in the nucleus. Reason: The evidence for mitochondrial matrix localization of CREB1 is limited. CREB1 is primarily a nuclear protein. Requires further investigation. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate annotation. CREB1 regulates Pol II transcription. Reason: Core biological process. IEA annotation consistent with IBA annotation. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be involved in TGF-beta signaling as a downstream transcriptional effector, but this is not a core pathway for CREB1. Reason: CREB1 may participate in TGF-beta responses through cross-talk with other signaling pathways, but TGF-beta signaling is not a core CREB1 function. |
| GO:0007613 memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 plays important roles in memory formation through activity-dependent gene expression in neurons. This is supported by extensive literature on CREB in synaptic plasticity and long-term memory. Reason: Well-documented role in memory but this is a neuron-specific phenotypic outcome of CREB1's transcriptional activity rather than a molecular function. Important for understanding CREB1 biology but downstream of core function. |
| GO:0007623 circadian rhythm | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: CREB1 phosphorylation in the suprachiasmatic nucleus (SCN) participates in circadian rhythm generation. However, circadian rhythm is not a core function of CREB1 - it is a context-dependent downstream effect of its transcriptional activity in specific cell types. Reason: While CREB1 may regulate clock genes in the SCN, circadian rhythm is not a core function. The deep research review focuses on cAMP-responsive transcription, neuronal plasticity, metabolism, cancer, and immune function without emphasis on circadian rhythms. This appears to be over-annotation based on tissue-specific phenotypic effects. |
| GO:0008542 visual learning | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may participate in visual learning through activity-dependent gene expression, similar to its role in memory formation. Reason: Phenotypic outcome of CREB1 transcriptional activity in specific neuronal contexts. Not a core molecular or cellular function. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be activated by various xenobiotic stimuli that signal through cAMP/PKA pathways. Reason: Context-dependent response, not a core function. CREB1 responds to many stimuli that activate upstream kinases. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 can negatively regulate gene expression in certain contexts, though it primarily functions as a transcriptional activator. Reason: CREB1 primarily activates transcription but can have repressive effects in specific contexts. Not the primary mode of action. |
| GO:0014823 response to activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by neuronal activity through Ca2+/CaMK and other pathways, mediating activity-dependent gene expression. Reason: Important for understanding CREB1's role in neurons but context-dependent. Core function is cAMP-responsive transcription. |
| GO:0030424 axon | IEA GO_REF:0000107 | UNDECIDED | Summary: CREB1 may be detected in axons but its primary site of function is the nucleus where it regulates transcription. Reason: CREB1 is primarily a nuclear protein. Axonal localization would be unusual and requires verification. May reflect transport or non-canonical function. |
| GO:0030544 Hsp70 protein binding | IEA GO_REF:0000107 | UNDECIDED | Summary: CREB1 may interact with Hsp70 chaperones for protein folding or stability. Reason: Limited evidence for functional significance of Hsp70 binding. May represent general chaperone interaction rather than specific functional binding. |
| GO:0032916 positive regulation of transforming growth factor beta3 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate TGF-beta3 expression through CRE elements in the TGF-beta3 promoter. Reason: Specific downstream target regulation, not a core function. CREB1 regulates many target genes. |
| GO:0033762 response to glucagon | IEA GO_REF:0000107 | ACCEPT | Summary: Glucagon signals through cAMP/PKA to activate CREB1 in hepatocytes, inducing gluconeogenic genes like PEPCK. This is a well-characterized metabolic role of CREB1. Reason: Well-documented response - glucagon activates CREB1 through cAMP/PKA in liver to regulate gluconeogenesis. Directly relevant to core cAMP-responsive function. Supporting Evidence: PMID:11522779 The phosphoenolpyruvate carboxykinase (PEPCK) promoter was used as a model system to explore the role of SRCAP in the regulation of transcription mediated by factors that utilize CBP as a coactivator |
| GO:0034670 chemotaxis to arachidonate | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be involved in arachidonate-mediated chemotaxis signaling. Reason: Context-dependent response, not a core CREB1 function. |
| GO:0035035 histone acetyltransferase binding | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 binds histone acetyltransferases CBP/p300 when phosphorylated at Ser-119. This is a core mechanism for transcriptional activation. Reason: Core molecular function. CBP and p300 are histone acetyltransferases that CREB1 recruits to activate transcription. The KID-KIX interaction is essential for CREB-mediated gene activation. Supporting Evidence: PMID:11522779 SRCAP binds to CBP amino acids 280-460, a region that is important for CBP to function as a coactivator for CREB |
| GO:0035094 response to nicotine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be activated by nicotine through neuronal signaling pathways. Reason: Context-dependent response to a specific stimulus, not a core function. |
| GO:0035497 cAMP response element binding | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of IBA annotation. CRE binding is the defining DNA binding specificity of CREB1. Reason: Core molecular function. IEA annotation consistent with IBA annotation. |
| GO:0036017 response to erythropoietin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be involved in erythropoietin signaling responses. Reason: Context-dependent signaling response, not a core function. |
| GO:0036120 cellular response to platelet-derived growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be activated by PDGF signaling through MAPK/RSK pathways. Reason: Context-dependent growth factor response. CREB1 responds to many upstream signals. |
| GO:0042220 response to cocaine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by cocaine in reward circuits through dopamine signaling and cAMP/PKA pathways. Reason: Context-dependent drug response in neurons, not a core function. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 regulates genes involved in apoptosis including BCL-2 family members (PMID:8798441). It generally promotes cell survival. Reason: CREB1 regulates apoptosis-related genes but this is a downstream phenotypic effect of its transcriptional activity, not a core function. Supporting Evidence: PMID:8798441 CREB proteins function as positive regulators of the translocated bcl-2 allele in t(14;18) lymphomas |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 can positively regulate apoptosis in certain contexts, though it more commonly promotes survival. Reason: Context-dependent effect on apoptosis. CREB1 primarily promotes survival but can have pro-apoptotic effects in some settings. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CREB1 generally promotes cell survival through activation of anti-apoptotic genes like BCL-2. Reason: CREB1 has pro-survival effects through transcriptional regulation of BCL-2 and other genes, but this is a downstream phenotypic effect. Supporting Evidence: PMID:8798441 CREB proteins function as positive regulators of the translocated bcl-2 allele |
| GO:0043278 response to morphine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by morphine through opioid receptor signaling. Reason: Context-dependent drug response, not a core function. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: CREB1 binds DNA in a sequence-specific manner to CRE elements. Parent term of more specific annotations. Reason: Core molecular function. CREB1 recognizes the CRE sequence specifically. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may respond to ethanol through various neuronal signaling pathways. Reason: Context-dependent drug response, not a core function. |
| GO:0045600 positive regulation of fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 promotes adipocyte differentiation through regulation of adipogenic genes in response to cAMP signaling. Reason: Cell type-specific differentiation role, downstream of core transcriptional function. |
| GO:0045722 positive regulation of gluconeogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 activates gluconeogenic genes like PEPCK in response to glucagon/cAMP signaling in hepatocytes. Reason: Important metabolic role in liver but tissue-specific downstream effect of core cAMP-responsive transcription function. Supporting Evidence: PMID:11522779 The phosphoenolpyruvate carboxykinase (PEPCK) promoter was used as a model system |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 positively regulates transcription when activated by phosphorylation. Reason: Core biological process. CREB1 is primarily a transcriptional activator. |
| GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 may facilitate preinitiation complex assembly through recruitment of coactivators that interact with basal transcription machinery. Reason: Mechanistically relevant to CREB1's role in transcriptional activation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 activates Pol II-dependent transcription when phosphorylated. Reason: Core biological process directly related to CREB1's molecular function as a transcriptional activator. |
| GO:0046889 positive regulation of lipid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate lipogenic gene expression in metabolic contexts. Reason: Metabolic downstream effect, not a core function. |
| GO:0048145 regulation of fibroblast proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate fibroblast proliferation through growth factor signaling. Reason: Cell type-specific phenotypic effect, not a core function. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate expression of genes involved in protein stability. CREB1 itself is stabilized by sumoylation. Reason: Indirect effect through transcriptional regulation or relates to CREB1's own regulation, not a core function. |
| GO:0060251 regulation of glial cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate glial cell proliferation through neuronal signaling. Reason: Cell type-specific phenotypic effect, not a core function. |
| GO:0071300 cellular response to retinoic acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may participate in retinoic acid responses through cross-talk with other signaling pathways. Reason: Context-dependent signaling response, not a core function. |
| GO:0071363 cellular response to growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by various growth factors through MAPK/RSK and other signaling pathways. Reason: General response category. Core function is cAMP-responsive transcription, but CREB1 also responds to growth factor signals. |
| GO:0071398 cellular response to fatty acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may respond to fatty acid signaling in metabolic contexts. Reason: Context-dependent metabolic response, not a core function. |
| GO:0071560 cellular response to transforming growth factor beta stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may participate in TGF-beta responses. Reason: Context-dependent signaling response, not a core function. |
| GO:1900273 positive regulation of long-term synaptic potentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 plays important roles in long-term potentiation (LTP) through activity-dependent gene expression required for synaptic plasticity. Reason: Well-documented neuronal function but this is a phenotypic outcome of CREB1's transcriptional activity in neurons, not a core molecular function. |
| GO:1902065 response to L-glutamate | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by glutamate signaling through Ca2+/CaMK pathways in neurons. Reason: Neuron-specific signaling response, not a core function. |
| GO:1903494 response to dehydroepiandrosterone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may respond to DHEA signaling. Reason: Context-dependent hormonal response, not a core function. |
| GO:1904181 positive regulation of membrane depolarization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate genes involved in neuronal excitability. Reason: Downstream phenotypic effect in neurons, not a core function. |
| GO:1990090 cellular response to nerve growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 is activated by NGF through MAPK/RSK pathways in neurons. Reason: Neuron-specific growth factor response, not a core function. |
| GO:1990314 cellular response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may be activated by IGF signaling through PI3K/AKT pathway. Reason: Context-dependent growth factor response, not a core function. |
| GO:1990589 ATF4-CREB1 transcription factor complex | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of IBA annotation. CREB1 forms complexes with ATF4. Reason: Valid cellular component. IEA annotation consistent with IBA annotation. |
| GO:1990763 arrestin family protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: CREB1 interacts with beta-arrestin1 (ARRB1) which has a nuclear function in GPCR signaling and histone acetylation (PMID:16325578). Reason: Specific protein binding annotation more informative than generic protein binding. ARRB1 interaction is functionally relevant for CREB-dependent transcription. |
| GO:1990910 response to hypobaric hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may respond to hypoxic stress. Reason: Context-dependent stress response, not a core function. |
| GO:2000224 regulation of testosterone biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CREB1 may regulate steroidogenic gene expression in gonadal cells. Reason: Tissue-specific downstream effect, not a core function. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: CREB1 localizes to the nucleoplasm where it functions as a transcription factor. Reason: Core cellular component. IDA annotation from immunofluorescence data. |
| GO:0005634 nucleus | NAS PMID:12871976 Induction of Grp78/BiP by translational block: activation of... | ACCEPT | Summary: CREB1 is a nuclear transcription factor. PMID:12871976 identifies CREB1 as a nuclear co-factor that forms complexes with ATF4. Reason: Core cellular component supported by literature. Supporting Evidence: PMID:12871976 we have identified the closely related ATF1 and CREB1 as nuclear co-factors that form in vivo complexes with endogenous ATF4 |
| GO:0005634 nucleus | NAS PMID:1655749 The cAMP-regulated enhancer-binding protein ATF-1 activates ... | ACCEPT | Summary: CREB1 is a nuclear transcription factor. Reason: Core cellular component. Supporting Evidence: PMID:1655749 The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:1655749 The cAMP-regulated enhancer-binding protein ATF-1 activates ... | ACCEPT | Summary: PMID:1655749 demonstrates that CREB family members (ATF-1 and CREB) activate transcription in response to PKA. Reason: Core biological process. Direct experimental evidence for transcriptional activation. Supporting Evidence: PMID:1655749 ATF-1 is as active as CREB in its ability to mediate the transcriptional effects of PKA |
| GO:0005634 nucleus | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: CREB1 is a nuclear protein. Reason: Core cellular component. Supporting Evidence: PMID:20102225 Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:20102225 Identification of bZIP interaction partners of viral protein... | ACCEPT | Summary: CREB1 regulates Pol II transcription. Reason: Core biological process. Supporting Evidence: PMID:20102225 Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:11522779 Regulation of cAMP-responsive element-binding protein-mediat... | ACCEPT | Summary: PMID:11522779 demonstrates that CREB mediates PKA-activated transcription through CRE elements in the PEPCK promoter. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:11522779 SRCAP functions as a coactivator for PKA-activated factors such as CREB |
| GO:0005634 nucleus | IDA PMID:11522779 Regulation of cAMP-responsive element-binding protein-mediat... | ACCEPT | Summary: CREB1 functions in the nucleus. Reason: Core cellular component. Supporting Evidence: PMID:11522779 2001 Aug 24. Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11522779 Regulation of cAMP-responsive element-binding protein-mediat... | ACCEPT | Summary: PMID:11522779 shows CREB activates Pol II transcription at the PEPCK promoter. Reason: Core biological process with direct experimental evidence. Supporting Evidence: PMID:11522779 transcription of a PEPCK chloramphenicol acetyltransferase (CAT) reporter gene activated by protein kinase A (PKA) is enhanced 7-fold by SRCAP |
| GO:0141156 cAMP/PKA signal transduction | IDA PMID:11522779 Regulation of cAMP-responsive element-binding protein-mediat... | ACCEPT | Summary: PMID:11522779 demonstrates CREB's role as a downstream effector of PKA signaling. Reason: Core biological process with direct experimental evidence. Supporting Evidence: PMID:11522779 SRCAP functions as a coactivator for PKA-activated factors such as CREB |
| GO:0141156 cAMP/PKA signal transduction | IDA PMID:25644539 Adenosine derived from ecto-nucleotidases in calcific aortic... | ACCEPT | Summary: PMID:25644539 demonstrates CREB1 involvement in cAMP/PKA signaling in the context of aortic valve calcification. Reason: Core biological process with experimental evidence. Supporting Evidence: PMID:25644539 Feb 2. Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-199298 | ACCEPT | Summary: Reactome pathway for AKT phosphorylation of CREB1 places CREB1 in nucleoplasm. Reason: Core cellular component supported by pathway database. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-199895 | ACCEPT | Summary: Reactome pathway for RSK1/2/3 phosphorylation of CREB. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-199917 | ACCEPT | Summary: Reactome pathway for MAPKAPK2 phosphorylation of CREB. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-199935 | ACCEPT | Summary: Reactome pathway for MSK1 activation of CREB. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2399996 | ACCEPT | Summary: Reactome pathway for AKT1 E17K mutant phosphorylation of CREB1. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-442724 | ACCEPT | Summary: Reactome pathway for RSK phosphorylation of CREB1. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9612501 | ACCEPT | Summary: Reactome pathway for SGK phosphorylation of CREB1. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9612514 | ACCEPT | Summary: Reactome pathway for p-S133 CREB binding to EGR1 promoter. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613451 | ACCEPT | Summary: Reactome pathway for CREB1 binding to ID1 and ID3 genes. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9623341 | ACCEPT | Summary: Reactome pathway for CREB1 binding to CCND1 promoter. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9662708 | ACCEPT | Summary: Reactome pathway for CREB binding to IL6 promoter. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9664332 | ACCEPT | Summary: Reactome pathway for CREB1 binding to IL-10 promoter. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9824653 | ACCEPT | Summary: Reactome pathway for CREB1 binding to MITF promoter. Reason: Core cellular component. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9825848 | ACCEPT | Summary: Reactome pathway for CREB1 at DCT promoter. Reason: Core cellular component. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CREB1 promotes cell survival through activation of anti-apoptotic genes like BCL-2. Reason: Downstream phenotypic effect of transcriptional activity. |
| GO:0042789 mRNA transcription by RNA polymerase II | IDA PMID:25644539 Adenosine derived from ecto-nucleotidases in calcific aortic... | ACCEPT | Summary: CREB1 mediates mRNA transcription by Pol II. Reason: Core biological process related to transcriptional function. Supporting Evidence: PMID:25644539 Feb 2. Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor. |
| GO:1904322 cellular response to forskolin | IDA PMID:25644539 Adenosine derived from ecto-nucleotidases in calcific aortic... | ACCEPT | Summary: Forskolin activates adenylyl cyclase and cAMP/PKA signaling, which activates CREB1. CREB1 is a key mediator of forskolin responses. Reason: Directly relevant to CREB1's core function in cAMP signaling. Forskolin is a standard tool for activating CREB through the cAMP/PKA pathway. Supporting Evidence: PMID:25644539 Feb 2. Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor. |
| GO:0014074 response to purine-containing compound | IDA PMID:25644539 Adenosine derived from ecto-nucleotidases in calcific aortic... | KEEP AS NON CORE | Summary: CREB1 responds to adenosine and other purine compounds through cAMP signaling. Reason: Related to cAMP signaling but general response category. Supporting Evidence: PMID:25644539 Feb 2. Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: PMID:28473536 analyzed DNA binding specificities of transcription factors including CREB1. Reason: Core molecular function describing DNA binding specificity. Supporting Evidence: PMID:28473536 Impact of cytosine methylation on DNA binding specificities of human transcription factors. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: CREB1 is a transcriptional activator. Reason: Core molecular function. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: CREB1 associates with chromatin at CRE-containing promoters. Reason: Valid cellular component. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: CREB1 is a Pol II-specific transcription factor based on TFClass database. Reason: Core molecular function. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 shows CREB1 activates gamma-globin gene expression through the G-CRE element. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:19861239 enforced expression studies with pLen-cJun and a Ggamma-promoter (-1500 to +36) luciferase reporter were completed; we observed a concentration-dependent increase in luciferase activity with pLen-cJun similar to that produced by CREB1 enforced expression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: CREB1 activates Pol II transcription. Reason: Core biological process. |
| GO:0071300 cellular response to retinoic acid | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CREB1 may participate in retinoic acid responses. Reason: Context-dependent signaling response. |
| GO:1990589 ATF4-CREB1 transcription factor complex | IDA PMID:12871976 Induction of Grp78/BiP by translational block: activation of... | ACCEPT | Summary: PMID:12871976 identifies CREB1 as forming complexes with ATF4 that activate the Grp78 promoter through ATF/CRE sites. Reason: Valid cellular component with direct experimental evidence. Supporting Evidence: PMID:12871976 we have identified the closely related ATF1 and CREB1 as nuclear co-factors that form in vivo complexes with endogenous ATF4 |
| GO:0019899 enzyme binding | IPI PMID:23382074 A high-confidence interaction map identifies SIRT1 as a medi... | ACCEPT | Summary: PMID:23382074 identifies CREB1 interaction with SIRT1 deacetylase. More informative than generic protein binding. Reason: Specific binding annotation. CREB1 interacts with various enzymes that regulate its activity. Supporting Evidence: PMID:23382074 Feb 4. A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. |
| GO:0007623 circadian rhythm | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Circadian rhythm annotation based on sequence similarity to mouse CREB1. While CREB1 participates in SCN signaling, circadian rhythm is not a core function. Reason: Over-annotation. CREB1's core function is cAMP-responsive transcription. Circadian rhythm involvement is tissue-specific and downstream of core function. |
| GO:0033762 response to glucagon | ISS GO_REF:0000024 | ACCEPT | Summary: Glucagon response is well-documented for CREB1 in hepatocytes. Reason: Well-characterized response directly related to cAMP/PKA signaling function. |
| GO:0045600 positive regulation of fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CREB1 promotes adipocyte differentiation. Reason: Cell type-specific downstream effect. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: CREB1 activates transcription. Reason: Core biological process. |
| GO:0046889 positive regulation of lipid biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CREB1 may regulate lipogenic genes. Reason: Metabolic downstream effect. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:9065434 Constitutive binding of the transcription factor interleukin... | ACCEPT | Summary: PMID:9065434 demonstrates CREB binding to the IL-2 promoter CRE. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:9065434 Constitutive binding of the transcription factor interleukin-2 (IL-2) enhancer binding factor to the IL-2 promoter. |
| GO:0005515 protein binding | IPI PMID:18160048 Lyl1 interacts with CREB1 and alters expression of CREB1 tar... | REMOVE | Summary: Generic protein binding from interaction with LYL1. Reason: Uninformative generic term. Supporting Evidence: PMID:18160048 Lyl1 interacts with CREB1 and alters expression of CREB1 target genes. |
| GO:0050821 protein stabilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: CREB1 may contribute to protein stabilization. Reason: Indirect effect, not a core function. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 demonstrates CREB1 transcription factor activity at gamma-globin promoter. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:19861239 Using chromatin immunoprecipitation assays we showed comparable in vivo cJun and CREB1 binding to the G-CRE region |
| GO:0010944 negative regulation of transcription by competitive promoter binding | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 shows competitive binding at the gamma-globin CRE where CREB1 and cJun can compete for binding. Reason: Valid regulatory mechanism - competition between transcription factors at shared binding sites. Supporting Evidence: PMID:19861239 Protein-protein interactions were confirmed between cJun/ATF-2 and CREB1/ATF-2 but not between CREB1 and cJun |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 shows CREB1 activates gamma-globin transcription. Reason: Core biological process with experimental evidence. Supporting Evidence: PMID:19861239 we observed a concentration-dependent increase in luciferase activity with pLen-cJun similar to that produced by CREB1 enforced expression |
| GO:0000791 euchromatin | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 shows CREB1 binding to the actively transcribed gamma-globin locus in euchromatin. Reason: Valid cellular component - CREB1 binds actively transcribed chromatin regions. Supporting Evidence: PMID:19861239 Epub 2009 Oct 27. cJun modulates Ggamma-globin gene expression via an upstream cAMP response element. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 demonstrates CREB1 binding to the gamma-globin G-CRE. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:19861239 we observed cJun and CREB1 binding to the G-CRE in vitro by electrophoretic mobility shift assay |
| GO:0035497 cAMP response element binding | IDA PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 demonstrates CREB1 binding to the G-CRE element. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:19861239 Using chromatin immunoprecipitation assays we showed comparable in vivo cJun and CREB1 binding to the G-CRE region |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:19861239 cJun modulates Ggamma-globin gene expression via an upstream... | ACCEPT | Summary: PMID:19861239 shows CREB1 interacts with c-Jun at the gamma-globin promoter. Reason: Valid molecular function - CREB1 interacts with other transcription factors. Supporting Evidence: PMID:19861239 Promoter pull-down assay followed by sequential western blot analysis confirmed co-localization of cJun, CREB1, and ATF-2 on the G-CRE |
| GO:0005515 protein binding | IPI PMID:21172805 TOX3 is a neuronal survival factor that induces transcriptio... | REMOVE | Summary: Generic protein binding from interaction with TOX3. Reason: Uninformative generic term. Supporting Evidence: PMID:21172805 Dec 15. TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex. |
| GO:0005515 protein binding | IPI PMID:18316612 Molecular basis of nuclear factor-kappaB activation by astro... | REMOVE | Summary: Generic protein binding from interaction with AEG-1. Reason: Uninformative generic term. Supporting Evidence: PMID:18316612 Molecular basis of nuclear factor-kappaB activation by astrocyte elevated gene-1. |
| GO:0005515 protein binding | IPI PMID:16325578 A nuclear function of beta-arrestin1 in GPCR signaling: regu... | REMOVE | Summary: Generic protein binding from interaction with beta-arrestin1 (ARRB1). Reason: Uninformative generic term. The ARRB1 interaction is better captured by GO:1990763 (arrestin family protein binding). Supporting Evidence: PMID:16325578 A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:8798441 CREB proteins function as positive regulators of the translo... | ACCEPT | Summary: PMID:8798441 demonstrates CREB binding to the bcl-2 CRE and transcriptional activation of the bcl-2 promoter. Reason: Core molecular function with experimental evidence. Supporting Evidence: PMID:8798441 Electrophoretic mobility shift assays with the bcl-2 CRE demonstrated complexes with mobilities identical to those with a consensus CRE |
| GO:0005634 nucleus | IDA PMID:8798441 CREB proteins function as positive regulators of the translo... | ACCEPT | Summary: CREB1 is a nuclear transcription factor. Reason: Core cellular component. Supporting Evidence: PMID:8798441 CREB proteins function as positive regulators of the translocated bcl-2 allele in t(14;18) lymphomas. |
| GO:0006468 protein phosphorylation | IDA PMID:8798441 CREB proteins function as positive regulators of the translo... | REMOVE | Summary: MISANNOTATION: CREB1 is a bZIP transcription factor that is extensively PHOSPHORYLATED by kinases (CaMK1/2/4, AKT, RPS6KA3/4/5, SGK1, TSSK4, HIPK2) at Ser-119, Ser-128, and Ser-257. PMID:8798441 describes "phosphorylated CREB was present in DHL-4 cells" - CREB1 is the SUBSTRATE of phosphorylation, not the enzyme. CREB1 has no kinase activity (EC number). This is a transcription factor that regulates bcl-2 expression when phosphorylated. The paper shows CREB1 being phosphorylated by upstream kinases like PKA and PKC, not CREB1 catalyzing phosphorylation. Reason: Incorrect annotation. CREB1 is phosphorylated by upstream kinases - it is a substrate, not an enzyme. CREB1 has no kinase domain or kinase activity. Supporting Evidence: PMID:8798441 Electrophoretic mobility shift assay with an antibody specific to the phosphorylated cAMP response-binding protein (CREB) demonstrated that phosphorylated CREB was present in DHL-4 cells |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:8798441 CREB proteins function as positive regulators of the translo... | ACCEPT | Summary: PMID:8798441 shows CREB proteins activate bcl-2 transcription through CRE elements. Reason: Core biological process with experimental evidence. Supporting Evidence: PMID:8798441 CREB proteins function as positive regulators of the translocated bcl-2 allele in t(14;18) lymphomas |
| GO:0005515 protein binding | IPI PMID:14506290 Identification of a family of cAMP response element-binding ... | REMOVE | Summary: Generic protein binding from interaction with CRTC3 coactivator. Reason: Uninformative generic term. CRTC interaction is better represented by GO:0001223 (transcription coactivator binding). Supporting Evidence: PMID:14506290 Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells. |
| GO:0007165 signal transduction | TAS PMID:2974179 Cyclic AMP-responsive DNA-binding protein - structure based ... | ACCEPT | Summary: PMID:2974179 describes the cloning of CREB and establishes its role in cAMP signal transduction. Reason: Core biological process. CREB1 is a key effector of cAMP signaling pathways. Supporting Evidence: PMID:2974179 Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)