Gene Report

Basic Information

Approved Symbol	CREBBP
Approved Name	CREB binding protein
Previous Symbol	RSTS
Previous Name	Rubinstein-Taybi syndrome
Symbol Alias	RTS, CBP, KAT3A
Location	16p13.3
Position	chr16:3775055-3930121 (-)
External Links	Entrez Gene: 1387 Ensembl: ENSG00000005339 UCSC: uc002cvv.3 HGNC ID: 2348
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin

Positive relationships between CREBBP and MDD (count: 0)

Positive relationships between CREBBP and other components at different levels (count: 0)

Positive relationship network of CREBBP in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between CREBBP and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
CREBBP	Crisafulli C, 2012	patients and normal controls		Participants were genotyped for 14 SNPs within CREB1, CREBBP...... Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. More...

Negative relationships between CREBBP and other components at different levels (count: 0)

CREBBP related SNPs in MK4MDD (count: 0)

CREBBP related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
CREB-binding protein	Q92793	0(0/0)	Gene mapped

CREBBP related GO terms (count: 47)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0008134	transcription factor binding	molecular function	IPI[15509593]
GO:0003700	sequence-specific DNA binding transcription factor activity	molecular function	TAS[7913207]
GO:0004871	signal transducer activity	molecular function	TAS[8028671]
GO:0002039	p53 binding	molecular function	IPI[9194565]
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0008270	zinc ion binding	molecular function	IEA
GO:0045893	positive regulation of transcription, DNA-dependent	biological process	IDA[11742995]; ISS
GO:0010467	gene expression	biological process	TAS
GO:0000790	nuclear chromatin	cellular component	IDA
GO:0016407	acetyltransferase activity	molecular function	IDA[11742995]
GO:0001666	response to hypoxia	biological process	TAS[15261140]
GO:0008589	regulation of smoothened signaling pathway	biological process	TAS[11001584]
GO:0018076	N-terminal peptidyl-lysine acetylation	biological process	IDA[12435739]
GO:0016573	histone acetylation	biological process	IDA[11742995]
GO:0001191	RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription	molecular function	IDA
GO:0007165	signal transduction	biological process	NAS[15261140]
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia	biological process	TAS
GO:0071456	cellular response to hypoxia	biological process	TAS
GO:0000987	core promoter proximal region sequence-specific DNA binding	molecular function	IDA
GO:0004402	histone acetyltransferase activity	molecular function	IDA[11742995]
GO:0001085	RNA polymerase II transcription factor binding	molecular function	IPI
GO:0005667	transcription factor complex	cellular component	IEA
GO:0042592	homeostatic process	biological process	NAS[15261140]
GO:0006367	transcription initiation from RNA polymerase II promoter	biological process	TAS
GO:0000123	histone acetyltransferase complex	cellular component	IEA
GO:0006461	protein complex assembly	biological process	TAS[7913207]
GO:0001078	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription	molecular function	IDA
GO:0005654	nucleoplasm	cellular component	TAS
GO:0016604	nuclear body	cellular component	IDA[15488321]
GO:0042733	embryonic digit morphogenesis	biological process	TAS[11001584]
GO:0006355	regulation of transcription, DNA-dependent	biological process	IDA[12169688]; TAS[15261140]
GO:0019048	virus-host interaction	biological process	IEA
GO:0001105	RNA polymerase II transcription coactivator activity	molecular function	TAS[11001584]
GO:0005737	cytoplasm	cellular component	IDA[12929931]
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA
GO:0007219	Notch signaling pathway	biological process	TAS
GO:0043426	MRF binding	molecular function	IDA[8621548]
GO:0003682	chromatin binding	molecular function	IEA
GO:0033554	cellular response to stress	biological process	TAS
GO:0030718	germ-line stem cell maintenance	biological process	IEA
GO:0003713	transcription coactivator activity	molecular function	IDA[12169688]; IDA[12929931]; IPI[8684459]
GO:0045087	innate immune response	biological process	TAS
GO:0044255	cellular lipid metabolic process	biological process	TAS
GO:0005515	protein binding	molecular function	IPI[16043483]
GO:0000940	condensed chromosome outer kinetochore	cellular component	IEA
GO:0005634	nucleus	cellular component	IC[12169688]; IDA[12929931]
GO:0001102	RNA polymerase II activating transcription factor binding	molecular function	TAS[11001584]

CREBBP related KEGG pathways (count: 12)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04350	tgf beta_signaling_pathway	TGF-beta signaling pathway	The transforming growth factor-beta (TGF-beta) family member...... The transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species ranging from worms and insects to mammals. A wide spectrum of cellular functions such as proliferation, apoptosis, differentiation and migration are regulated by TGF-beta family members. TGF-beta family member binds to the Type II receptor and recruits Type I, whereby Type II receptor phosphorylates and activates Type I. The Type I receptor, in turn, phosphorylates receptor-activated Smads ( R-Smads: Smad1, Smad2, Smad3, Smad5, and Smad8). Once phosphorylated, R-Smads associate with the co-mediator Smad, Smad4, and the heteromeric complex then translocates into the nucleus. In the nucleus, Smad complexes activate specific genes through cooperative interactions with other DNA-binding and coactivator (or co-repressor) proteins. More...
hsa05016	huntingtons disease	Huntington's disease	Huntington disease (HD) is an autosomal-dominant neurodegene...... Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2+ handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2+ responses in HD MSN and mitochondrial Ca2+ overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction. More...
hsa04720	long term_potentiation	Long-term potentiation	Hippocampal long-term potentiation (LTP), a long-lasting inc...... Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII). Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP). More...
hsa05211	renal cell_carcinoma	Renal cell carcinoma	Renal cell carcinoma (RCC) is a heterogenous term comprising...... Renal cell carcinoma (RCC) is a heterogenous term comprising a group of neoplasms of renal origin. There are 4 major histologic subtypes of RCC: conventional (clear cell RCC, 75%), papillary (15%), chromophobic (5%), and collecting duct (2%). Multiple genes are involved in the molecular pathogenesis of RCC. VHL is a tumor suppressor gene responsible for hereditary (von Hippel-Lindau) and sporadic variants of conventional (clear cell) RCC. In the absence of VHL, hypoxia-inducible factor alpha (HIF-alpha) accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. An oncogene, MET has been found to be mutant in cases of hereditary papillary renal cancer (HPRC), although the incidence of c-MET mutations is low in sporadic papillary RCC. Once activated, MET mediates a number of biological effects including motility, invasion of extracellular matrix, cellular transformation, prevention of apoptosis and metastasis formation. Mutations in the fumarate hydratase (FH) gene cause hereditary leiomyomatosis and renal cancer syndrome (HLRCC) papillary renal tumors, although the incidence of FH mutations in sporadic tumors is unknown. Loss of functional FH leads to accumulation of fumarate in the cell, triggering inhibition of HPH and preventing targeted pVHL-mediated degradation of HIF-alpha. BHD mutations cause the Birt-Hogg-Dube syndrome and its associated chromophobe, hybrid oncocytic, and conventional (clear cell) RCC. The incidence of BHD mutations in sporadic renal tumors is not known. More...
hsa04330	notch signaling_pathway	Notch signaling pathway	The Notch signaling pathway is an evolutionarily conserved, ...... The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch proteins (Notch1-Notch4 in vertebrates) are single-pass receptors that are activated by the Delta (or Delta-like) and Jagged/Serrate families of membrane-bound ligands. They are transported to the plasma membrane as cleaved, but otherwise intact polypeptides. Interaction with ligand leads to two additional proteolytic cleavages that liberate the Notch intracellular domain (NICD) from the plasma membrane. The NICD translocates to the nucleus, where it forms a complex with the DNA binding protein CSL, displacing a histone deacetylase (HDAc)-co-repressor (CoR) complex from CSL. Components of an activation complex, such as MAML1 and histone acetyltransferases (HATs), are recruited to the NICD-CSL complex, leading to the transcriptional activation of Notch target genes. More...
hsa04630	jak stat_signaling_pathway	Jak-STAT signaling pathway	The Janus kinase/signal transducers and activators of transc...... The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors. More...
hsa05215	prostate cancer	Prostate cancer	The identification of key molecular alterations in prostate-...... The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes that catalyze conjunction of glutathione with harmful, electrophilic molecules, thereby protecting cells from carcinogenic factors. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by such carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. After therapeutic reduction in the levels of testosterone and dihydrotestosterone, the emergence of androgen-independent prostate cancer has been associated with mutations in the androgen receptor (AR) that permit receptor activation by other ligands, increased expression of androgen receptors accompanying AR amplification, and ligand-independent androgen-receptor activation. More...
hsa04520	adherens junction	Adherens junction	Cell-cell adherens junctions (AJs), the most common type of ...... Cell-cell adherens junctions (AJs), the most common type of intercellular adhesions, are important for maintaining tissue architecture and cell polarity and can limit cell movement and proliferation. At AJs, E-cadherin serves as an essential cell adhesion molecules (CAMs). The cytoplasmic tail binds beta-catenin, which in turn binds alpha-catenin. Alpha-catenin is associated with F-actin bundles directly and indirectly. The integrity of the cadherin-catenin complex is negatively regulated by phosphorylation of beta-catenin by receptor tyrosine kinases (RTKs) and cytoplasmic tyrosine kinases (Fer, Fyn, Yes, and Src), which leads to dissociation of the cadherin-catenin complex. Integrity of this complex is positively regulated by beta -catenin phosphorylation by casein kinase II, and dephosphorylation by protein tyrosine phosphatases. Changes in the phosphorylation state of beta-catenin affect cell-cell adhesion, cell migration and the level of signaling beta-catenin. Wnt signaling acts as a positive regulator of beta-catenin by inhibiting beta-catenin degradation, which stabilizes beta-catenin, and causes its accumulation. Cadherin may acts as a negative regulator of signaling beta-catenin as it binds beta-catenin at the cell surface and thereby sequesters it from the nucleus. Nectins also function as CAMs at AJs, but are more highly concentrated at AJs than E-cadherin. Nectins transduce signals through Cdc42 and Rac, which reorganize the actin cytoskeleton, regulate the formation of AJs, and strengthen cell-cell adhesion. More...
hsa04110	cell cycle	Cell cycle	Mitotic cell cycle progression is accomplished through a rep...... Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. More...
hsa04916	melanogenesis	Melanogenesis	Cutaneous melanin pigment plays a critical role in camouflag...... Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism. More...
hsa05200	pathways in_cancer	Pathways in cancer
hsa04310	wnt signaling_pathway	Wnt signaling pathway	Wnt proteins are secreted morphogens that are required for b...... Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin. More...

CREBBP related BioCarta pathways (count: 14)

ID	Name	Brief Description	Full Description
Literature-origin BioCarta pathway
NTHI_PATHWAY	nthi pathway	NFkB activation by Nontypeable Hemophilus influenzae	The role of Hemophilus influenzae in ear infections and chro...... The role of Hemophilus influenzae in ear infections and chronic obstructive pulmonary disease includes the induction of an inflammatory response through activation of the transcription factor NF-kB. In addition to activation of inflammatory cytokine genes like IL-1 and TNF, H. influenzae activates TLR2 expression and genes involved in mucus production. Hemophilus influenzae activates NF-kB by multiple mechanisms, starting with activation of the Toll-like receptor 2 (TLR2) by the p16 protein in the H. influenzae outer membrane. TLR2 plays a key role in innate immune responses and is expressed in high levels in lymphoid cells as well as low levels in epithelial cells. The role of TLR2 was supported by blocking NF-kB activation with a dominant negative TLR2 and increasing it with transfection of a normal TLR2 gene. TLR2 in turn activates TAK1, which activates two divergent signaling pathways. One of these pathways leads to IkB kinase activation, IkB phosphorylation and degradation, releasing the NF-kB heterodimer to translocate into the nucleus and activate transcription of target genes. In the alternate pathway, TAK1 also activates NF-kB through a Map kinase pathway, activating p38 and NF-kB in a nuclear translocation independent manner. Investigation of the mechanisms of H. influenzae signaling involved in NF-kB activation may provide the information needed to develop better treatments for inflammatory conditions caused by this pathogen. Other pathways modulate the role of NF-kB in H. influenzae pathogenesis. Glucocorticoids widely used as anti-inflammatory drugs increase TLR2 activation by H. influenzae through the NIK/I-kB kinase pathway, while they repress the p38 dependent activation of NF-kB. The repression of the p38 pathway by glucocorticoids occurs through activation of the MAP kinase phosphatase-1 (MKP-1) which dephosphorylates and deactivates p38. Another aspect of the inflammatory response to H. influenzae infection is the production of excessive mucus, contributing to the overall symptoms of infection. NF-kB activation of the Muc2 gene contributes to mucus overproduction, in addition to H. influenzae activation of the TGF-beta receptor, activating SMAD transcription factors SMAD3 and SMAD4. Understanding mechanisms that modify H. influenzae signaling will contribute to further understanding the pathogenesis and treatment of ear infections and chronic obstructive pulmonary disease. More...

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
NFAT_PATHWAY	nfat pathway	NFAT and Hypertrophy of the heart (Transcription in the broken heart)	Hypertrophy associated with both hypertension and obstructio...... Hypertrophy associated with both hypertension and obstruction to ventricular outflow leads to pathologic cardiac growth and it is associated with increase morbidity and mortality. Symptomatic ventricular disease takes a growing toll on the health of nations. As other cardiovascular diseases such as stroke and myocardial infraction are in decline as causes of mortality, the heart failure problem becomes increasingly urgent. Congenital heart defects occur in 1% of live births and fetal heart malformations are implicated in many pregnancies that end in still-birth or spontaneous abortion. The current paradigm suggests that the heart adapts to excess of hemodynamic loading by compensatory hypertrophy, which under condition of persistent stress, over time evolves into dysfunction and myocardial failure. There is considerable evidence that direct effects of increased mechanical stress are sensed within the ventricular wall and that signals critical for the generation of growth responses. Despite compelling statistics we still do not understand biochemically why heart defects are so prevalent. A single transcriptional regulator initially associated with the activation of the T-cells More...
VDR_PATHWAY	vdr pathway	Control of Gene Expression by Vitamin D Receptor	The vitamin D receptor, VDR is the mediator of all genomic a...... The vitamin D receptor, VDR is the mediator of all genomic actions of vitamin D3 and its analogs. It belongs to a family of ligand induced transcription factors, nuclear receptors (NRs). Vitamin D3 is the main regulator of calcium homeostasis and is critical in bone formation. It is also involved in controlling cellular growth, differentiation and apoptosis, which makes synthetic vitamin D3 analogues interesting for therapy of such diseases as cancer and psoriasis. NRs are comprised of: an amino-terminal activation function domain AF-1; the DNA-binding domain; a hinge region; and a carboxy-terminal ligand-binding domain containing a second activation function, AF-2. VDR acts primarily as a heterodimer with the retinoid X receptor (RXR) on vitamin D response elements (VDREs). It interacts with the transcription machinery and nuclear receptor coactivators or corepressors to regulate target gene activity. NRs coregulators can be divided into 3 major classes: 1)ATP-dependent chromatin remodeling complexes that are involved in the location and association of nucleosomes with DNA; 2) Enzymes that catalyze modifications of histone tails to regulate histone-histone and histone-DNA interactions 3) General transcription factors adaptors that bridge the functions between regulators and basal transcription factors. A novel multifunctional ATP-dependent chromatin remodeling complex c WINAC directly interacts with the vitamin D receptor. It contains BRG1 or hBRM as ATPase subunits as all SWI/SNF complexes do, but it also has subunits associated with DNA replication (TopoII_ and CAF-1p150) and transcript elongation through nucleosomes (FACTP140) not found before in SWI/SNF complexes. WINAC also contains the Williams syndrome transcription factor (WSTF). WSTF appears to function as a platform protein for the assembly of components in WINAC, and it interacts directly with the vitamin D receptor in a ligand-independent manner. WINAC and vitamin Dreceptor are targeted to vitamin D responsive promoters in the absence of ligand to both positively and negatively regulated genes. WINAC may rearrange the nucleosome array around the positive and negative VDREs, thereby facilitating the coregulatory complexes access for further transcription control. Upon ligand binding, two HAT complexes, p160/CBP and TRRAP/PCAF, coactivate the NR function. The p160 proteins (SRC protein family) interact directly with an NR activation surface AF2 and serve as platforms for the recruitment of histone-modifying enzymes, including CBP/p300 and methyltransferases. The SRC/p160 family members SRC-1 and p/CIP, as well as CBP and p300 contain intrinsic histone acetyltransferase activity(HAT). Both the HAT activity and the histone methyltransferase activity may cooperate in histone modification and facilitate nucleosome remodeling and recruitment of transcriptional machinery. A third group of coactivators is represented by thyroid receptor-associated proteins (TRAP)/vitamin D receptor-interacting proteins (DRIP). This complex may play a role by directly contacting the basal transcriptional machinery. As the VDR/RXR heterodimer also represses transcription in a ligand-dependent manner through negative VDRE (nVDRE), a number of corepressor proteins such as NCoR and ALIEN may also be recruited to the surface of the receptor. They, too function as platforms but serve to recruit enzymes such as histone deacetylases. WINAC association with VDR facilitates targeting of a putative corepressor complex to the nVDRE More...
SET_PATHWAY	set pathway	Granzyme A mediated Apoptosis Pathway	One mechanism used by cytotoxic T cells to kill tumor cells ...... One mechanism used by cytotoxic T cells to kill tumor cells and virus-infected cells is the release of perforin and granzyme proteins. Perforin proteins form pores in the membranes of the attacked cell, allowing the entry of Granzyme A and Granzyme B. Granzyme B induces caspase activation and cleavage of factors like ICAD, releasing DFF40 to fragment DNA, one of the hallmarks of apoptotic cell death. Granzyme A is also an abundant granzyme released by cytotoxic T cells and is important in cytotoxic T cell induced apoptosis, activating caspase independent pathways. Once in a cell, Granzyme A activates DNA nicking by the recently identified DNAse NM23-H1, a tumor suppressor gene product whose expression is reduced in transformed, metastatic cells. The previous identification of NM23-H1 as a tumor suppressor indicates that its DNAse activity plays an important role in immune surveillance to prevent cancer through the induction of tumor cell apoptosis. The activation of NM23-H1 occurs indirectly, through the cleavage of proteins that inhibit NM23-H1 in the SET complex, which includes SET, Ape1, pp32 and HMG2. SET is a substrate for the Granzyme A protease, and SET cleavage relieves NM23-H1 inhibition to cause apoptotic DNA degradation. In addition to inhibiting NM23-H1, SET has nucleosome assembly activity and also may help the interaction of transcriptional regulation with chromatin structure by interacting with the transcriptional coactivator CBP. The targets of Granzyme A found in the SET complex also have other important functions. Ape1 repairs oxidative DNA damage, reduces transcription factors involved in immediate early responses, and its cleavage by Granzyme A may contribute to DNA degradation and apoptosis. HMG2 is an acidic chromatin-associated protein that bends DNA, alters chromatin structure and alters the accessibility of genes for transcription. In addition to acting as a nucleosome assembly factor and an inhibitor of NM23-H1, SET inhibits DNA and histone methylation by the CBP transcriptional coactivator. The tumor suppressor pp32 is not cleaved by Granzyme A but is part of the SET complex. Other targets of Granzyme A include nuclear lamins responsible for maintaining nuclear structure and histones, the basic building blocks of chromatin structure. The common involvement of the proteins of the SET complex in chromatin structure and DNA repair suggest that they work together to protect chromatin and DNA structure and that inactivation of the complex contributes to apoptosis by blocking the maintenance of DNA and chromatin structural integrity. More...
RELA_PATHWAY	rela pathway	Acetylation and Deacetylation of RelA in The Nucleus
PITX2_PATHWAY	pitx2 pathway	Multi-step Regulation of Transcription by Pitx2	Many transcription factors play essential roles in normal de...... Many transcription factors play essential roles in normal development by determining the proliferation and differentiation of cells. The coordinated transcriptional control of proliferation in specific developmental cell types is crucial in multiple developmental settings. One of a family of three bicoid-related transcription factors, Pitx2 acts downstream of the extracellular signaling protein Wnt to drive proliferation of cells with specific developmental fates, including cells in the pituitary, cardiac outflow region, and muscle. Wnt binds to Frizzled, a G-protein coupled receptor, activating homologs of the Drosophila Disheveled protein. Activation of Frizzled and Disheveled inhibits the kinase GSK-3 beta, part of a protein complex in the absence of Wnt signaling, causing beta-catenin protein to accumulate in the cytoplasm. Beta-catenin is known to alter the function of transcription factors like TCF/Lef. One result of Wnt signaling is activation of the transcription factor Lef by beta-catenin, inducing Pitx2 expression. Wnt activation also changes Pitx2 from a repressor to an activator by causing transcriptional corepressors like histone deacetylase 1 (HDAC1) bound to Pitx2 to be exchanged for coactivators. With coactivators bound, Pitx2 activates transcription of genes that regulate the cell cycle like Cyclin D2. Different coactivators are recruited by Pitx2 and other transcription factors like Myc to the Cyclin D2 promoter, with CBP/p300 recruited first, followed by NLI/Ldb/CLIM, Tip60/TRRAP, and PBP coactivators. Many of these coactivators help to alter histone acetylation and chromatin structure as part of transcriptional activation. The activation of cell cycle genes by Pitx2 ultimately stimulates the proliferation of specific cell types with the confluence of tissue-specific gene expression, growth factor signaling and coactivator recruitment. More...
CSK_PATHWAY	csk pathway	Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor	Interaction of T cell receptor with specific antigen in the ...... Interaction of T cell receptor with specific antigen in the context of MHC II activates a signal transduction pathway that leads to T cell activation. In the T cell receptor signaling pathway, the src family kinases Lck and Fyn are activated to phosphorylate proteins in the T cell receptor complex which recruit and activate the ZAP70 kinase. The activation of ZAP70 phosphorylates downstream targets that activate MAP kinase pathways and cause T cell activation. The CD45 phosphorylase also plays a role in T cell receptor signaling, dephosphorylated Lck and Fyn to activate them. Other factors modulate T cell receptor activation. Csk (COOH-terminal Srk kinase) phosphorylates Lck and deactivates it, opposing the action of CD45. The phosphorylation of Lck by Csk inhibits T cell receptor signaling and inhibits T cell activation. Csk activity is regulated in T cells by PKA, the cAMP-dependent protein kinase activated by the second messenger cAMP. The activity of Csk also appears to depend on other factors such as CBP, which recruits Csk to the plasma membrane in lipid rafts where other signaling factors such the T cell receptor complex are localized. CBP also directly activates Csk. More...
CARM_ER_PATHWAY	carm er_pathway	CARM1 and Regulation of the Estrogen Receptor	Several forms of post-translational modification regulate pr...... Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. The methylation activity of CARM1 modulates the activity of specific transcriptional regulators. CARM1 acts as a coactivator for the myogenic transcription factor Mef2c, and is necessary for normal muscle cell differentiation. The estrogen receptor is another transcription factor that uses CARM1 as one of several coactivators, acting synergistically with CBP through the Grip1 member of the p160 family of coactivators. The interaction of estrogen receptor with various ligand-dependent coactivators may produce the tissue selective response of some estrogen receptor ligands like tamoxifen. More...
TGFB_PATHWAY	tgfb pathway	TGF beta signaling pathway	TGF-beta regulates growth and proliferation of cells, blocki...... TGF-beta regulates growth and proliferation of cells, blocking growth of many cell types. The TGF-beta receptor includes type 1 and type 2 subunits that are serine-threonine kinases and that signal through the SMAD family of transcriptional regulators. Defects in TGF-beta signaling, includes mutation in SMADs, have been associated with cancer in humans. Prior to activation, receptor regulated SMADs are anchored to the cell membrane by factors like SARA (SMAD Anchor for Receptor Activation) that brings the SMADs into proximity of the TGF receptor kinases. Binding of TGF induces phosphorylation and activation of the TGF-beta R1 receptor by the TGF-beta R2 receptor. The activated TGF-beta R1 phosphorylates SMAD2 and SMAD3, which bind to the SMAD4 mediator to move into the nucleus and form complexes that regulate transcription. SMADs regulate transcription in several ways, including binding to DNA, interacting with other transcription factors, and interacting with transcription corepressors and coactivators like p300 and CBP. SMAD-7 represses signaling by other SMADs to down-regulate the system. Other signaling pathways like the MAP kinase-ERK cascade are activated by TGF-beta signaling, modulate SMAD activation. SnoN also regulates TGF-beta signaling, by binding to SMADs to block transcriptional activation. TGF-beta signaling causes degradation of SnoN, releasing SMADs to regulate transcription, and also activates expression of SnoN, to down-regulate SMAD signaling at later times. More...
PML_PATHWAY	pml pathway	Regulation of transcriptional activity by PML	The PML nuclear bodies are ring-shaped nuclear substructures...... The PML nuclear bodies are ring-shaped nuclear substructures associated with the regulation of transcription, transformation, cell growth, and apoptosis and are characterized by the presence of the protein PML. The activities of PML as a tumor suppressor and apoptosis inducing factor are exerted through the numerous proteins it interacts with in the PML-nuclear bodies including the tumor suppressor p53. DNA damage induced activation of p53-dependent apoptosis requires PML. PML acts as a coactivator for p53 and increases acetylation of p53 by the transcriptional coactivator CBP. This acetylation of p53 is reversed by the deacetylase SirT1, the human homolog of the yeast gene Sir2, and this deacetylation opposes the transcriptional activation of p53. The tumor suppressor Rb also interacts with the PML nuclear body, increasing transcriptional repression of genes involved in cell cycle progression, suggesting that PML may affect cellular transformation through more than one mechanism. PML interacts directly with Ubc9, which modifies PML through the attachment of the ubiquitin-like peptide Sumo-1. Sumo-1 modification of PML is not necessary for the nuclear bodies to form, but may affect the recruitment of proteins that interact with PML. PML is involved in non-p53 mediated apoptotic pathways, such as DAXX-mediated apoptosis induced by Fas and TNF and regulates the transcriptional repressor activity of Daxx. The sequestration of Daxx by the PML nuclear bodies relieves the repression of other transcription factors like Pax3 by Daxx. Tumor suppression by PML may in general involve the formation of specific regulatory transcription complexes, including those with DAXX, p53 and CBP. Factors that affect the assembly of PML into the PML nuclear bodies affect the proliferation and transformation of cells. Viral early proteins can interact with PML to disrupt the nuclear bodies, allowing increased proliferation of cells and reduced apoptosis, good conditions for DNA virus infection. Another factor that disrupts the formation of PML nuclear bodies is a translocation between the PML and RAR-alpha genes found in acute promyelocytic leukemia (APL) patients. Binding of retinoic acid to the RAR-alpha steroid hormone receptor activates transcription of retinoic-acid responsive genes. The translocation found in APL patients creates two chimeric proteins, RARalpha-PML and PML-RARalpha. Retinoic acid given to APL patients causes the reappearance of nuclear bodies, and the reversal of cellular transformation, effecting a cure for these patients. More...
PPARA_PATHWAY	ppara pathway	Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha)	The most recognized mechanism by which peroxisome proliferat...... The most recognized mechanism by which peroxisome proliferators regulated gene expresssion is through a PPAR/RXR heterodimeric complex binding to a peroxisome proliferator-response element (PPRE) (classical mechanism). However, there are the possibility of several variations on this theme: 1). The peroxisome proliferator interacts with PPAR that preexists as a DNA complex with associated corepressors proteins. The interaction with ligand causes release of the corepressor and association with a coactivator, resulting in the classical mechanism. 2). The peroxisome proliferator interacts with PPAR as a soluble member of the nucleus. The binding of ligand results in RXR heterodimerization, DNA binding and coactivator recruitment. 3). In this scenario, PPAR exists in the cytosol, perhaps complexed to heat shock protein 90 and/or other chaperones. Binding of peroxisome proliferator causes a conformational change and translocation into the nucleus. Scenarios 4 and 5 require regulation of gene expression via non-classical mechanisms: 4). PPAR is capable of interacting with, and forming DNA binding heterodimers with, several nuclear receptors including the thyroid hormone receptor. The binding site for this non-RXR heterodimer need not be the classic DR-1 motif found in the PPRE. 5). PPAR may participate in the regulation of gene expression witout binding to DNA. By association with transcription factors such as c-jun or p65, PPAR diminishes the ability of AP1 or NFB to bind to their cognate DNA sequences, respectively. Also shown in this scheme are two means to modify the peroxisome proliferator response. Most importantly, growth factor signaling has a pronounced affect on PPAR via post-translational modification. PPAR is a phosphoprotein and its activity is affected by insulin. Several kinase pathways affects PPARa's activity, although the specific kinases and phosphorylation sites have not been conclusively determined. More...
IL7_PATHWAY	il7 pathway	IL-7 Signal Transduction	IL-7 is a key cytokine in the immune system, essential for n...... IL-7 is a key cytokine in the immune system, essential for normal development of B cells and T cells. Mice with the IL-7 receptor deleted lack B and T cells. Some humans with SCID (severe combined immunodeficiency disease) also have mutation of their IL-7 receptor gene leading to an absence of T cells and greatly impaired B cell production. The IL-7 receptor includes two polypeptides, a gamma chain and an alpha chain. The alpha-chain is unique to the IL-7 receptor while several other cytokines use the same gamma receptor chain as IL-7, including IL-2, IL-4, IL-9, IL-15 and IL-21. Binding of IL-7 to the alpha chain leads to dimerization of the alpha and gamma chains. JAK3 associated with the gamma chain tyrosine phosphorylates the alpha chain after dimerization. The importance of JAK3 in IL-7 signaling is supported by the similarity of the immune defects in JAK3 knockout mice and IL-7 knockout mice. The phosphorylated alpha chain serves as the site for recruiting other signaling molecules to the complex to be phosphorylated and activated, including STAT5, src kinases, PI3 kinase, Pyk2 and Bcl2 proteins. Some targets of IL-7 signaling contribute to cellular survival, including Bcl2 and Pyk2. Other targets contribute to cellular proliferation, including PI3 kinase, src family kinases (lck and fyn) and STAT5. The transcription factor STAT5 contributes to activation of multiple different downstream genes in B and T cells and may contribute to VDJ recombination through alteration of chromatin structure. The cell survival and cell proliferation signals induced by IL-7 combine to induce normal B and T cell development. More...
CARM1_PATHWAY	carm1 pathway	Transcription Regulation by Methyltransferase of CARM1	Several forms of post-translational modification regulate pr...... Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. More...
WNT_PATHWAY	wnt pathway	WNT Signaling Pathway	Wnt family members are secreted glycoproteins who bind to ce...... Wnt family members are secreted glycoproteins who bind to cell surface receptors such as Frizzled. Wnt members can play a role in the expression of many genes by interacting with multiple disparate signaling pathways. Shown is the Wnt/beta-catenin pathway. More...

CREBBP related Reactome pathways (count: 5)

ID	Name	Description
Gene mapped Reactome pathways
REACT_71	gene expression	Gene Expression covers the process of transcription of mRNA ...... Gene Expression covers the process of transcription of mRNA genes, the processing of pre-mRNA, and its subsequent translation to result in a protein. The expression of non-protein-coding genes is not included in this section yet. However, the transcription of RNAs other than mRNA is described in the section on transcription; in the sections 'RNA Polymerase I Transcription', and 'RNA Polymerase III Transcription'. More...
REACT_14835	notch hlh_transcription_pathway	THE NOTCH-HLH TRANSCRIPTION PATHWAY: Notch signaling was fir...... THE NOTCH-HLH TRANSCRIPTION PATHWAY: Notch signaling was first identified in Drosophila, where it has been studied in detail at the genetic, molecular, biochemical and cellular levels. In Drosophila, Notch signaling to the nucleus is thought always to be mediated by one specific DNA binding transcription factor, Suppressor of Hairless. In mammals, the homologous genes are called CBF1. All three of the co-repressor proteins have been shown to be necessary for proper gene regulation during Notch signaling in vivo. In mammals, the same general pathway and mechanisms are observed, where CSL proteins are bifunctional DNA binding transcription factors. Mammalian CSL Corepressor Complexes: In the absence of activated Notch signaling, DNA-bound CSL proteins recruit a corepressor complex to maintain target genes in the repressed state until Notch is specifically activated. The mammalian corepressor complexes include NCOR complexes, but may also include additional corepressor proteins, such as SHARP. The exact composition of the CSL NCOR complex is not known, but in other pathways the core NCOR corepressor complex includes at least one NCOR protein. In some contexts, the core NCOR corepressor complex may also recruit additional corepressor proteins or complexes, such as the SIN3 complex, which consists of SIN3. The CSL corepressor complex also includes a bifunctional cofactor, SKIP, that is present in both CSL corepressor complexes and CSL coactivator complexes, and may function in the binding of NICD and displacement of the corepressor complex during activated Notch signaling. Mammalian CSL Coactivator Complexes: Upon activation of Notch signaling, cleavage of the transmembrane Notch receptor releases the Notch Intracellular Domain. The resulting CSL-NICD binary complex then recruits an additional coactivator, Mastermind. There is evidence that Mam also can subsequently recruit specific kinases that phosphorylate NICD, to downregulate its function and turn off Notch signaling. Combinatorial Complexity in Transcription Cofactor Complexes: HDAC9 has at least 7 splice isoforms, with some having distinct interaction and functional properties. Isoforms 6 and 7 interact with NCOR1. Isoforms 1 and 4 interact with MEF2 , which is a specific DNA-binding cofactor for a subset of HLH proteins. Isoform 3 interacts with both NCOR1 and MEF2. Although many HDACs only have one or two isoforms, this complexity for HDAC9 illustrates the level of transcript complexity and functional specificity that such general transcriptional cofactors can have. More...
REACT_602	metabolism of_lipids_and_lipoproteins	Lipids are hydrophobic but otherwise chemically diverse mole...... Lipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphingolipids, eicosanoids, cholesterol, bile salts, steroid hormones, and fat-soluble vitamins, and function as a major source of energy (fatty acids, triacylglycerols, and ketone bodies), are major constituents of cell membranes (cholesterol and phospholipids), play a major role in their own digestion and uptake (bile salts), and participate in numerous signaling and regulatory processes (steroid hormones, eicosanoids, and sphingolipids). Because of their poor solubility in water, most lipids in extracellular spaces in the human body are found as complexes with specific carrier proteins. Regulation of the formation and movement of these lipoprotein complexes is a critical aspect of human lipid metabolism, and lipoprotein abnormalities are associated with major human disease processes including atherosclerosis and diabetes. Aspects of lipid metabolism currently annotated in Reactome include lipid digestion, trafficking of dietary sterols, triacylglycerol synthesis (fatty acid synthesis and triacylglycerol assembly), hormone-sensitive lipase-mediated triacylglycerol breakdown, and beta-oxidation of fatty acids, ketone body metabolism (synthesis and utilization), the synthesis of cholesterol, bile salts, and steroid hormones, and sphingolipid metabolism. Three aspects of lipoprotein function are currently annotated: chylomicron-mediated lipid transport, HDL (high density lipoprotein)-mediated lipid transport, and LDL (low density lipoprotein) endocytosis and degradation. More...
REACT_12627	generic transcription_pathway	OVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of ge...... OVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or tissue-specific regulation of differential gene transcription is mediated. Of the three major classes of DNA polymerase involved in eukaryotic gene transcription, Polymerase II generally regulates protein-encoding genes. Figure 1 shows a diagram of the various components involved in cell-specific regulation of Pol-II gene transcription. Core Promoter: Pol II-regulated genes typically have a Core Promoter where Pol II and a variety of general factors bind to specific DNA motifs: i: the TATA box and transcription repressor. The DRIP co-activator complex was originally identified and named as a specific complex associated with the Vitamin D Receptor member of the nuclear receptor family of transcription factors. Similarly, the TRAP co-activator complex was originally identified as a complex that associates with the thyroid receptor. It was later determined that all of the components of the DRIP complex are also present in the TRAP complex, and the ARC complex. In addition, these various transcription co-activator proteins identified in mammalian cells were found to be the orthologues or homologues of the Mediator. The Mediator proteins were originally identified in yeast by Kornberg and colleagues, as complexes associated with DNA polymerase. In higher organisms, Adapter complexes bridge between the basal transcription factors. For example, the DRIP205 / TRAP220 proteins are now identified as Mediator 1 , based on homology with yeast Mediator 1. Example Pathway: Specific Regulation of Target Genes During Notch Signaling: One well-studied example of cell-specific regulation of gene transcription is selective regulation of target genes during Notch signaling. Notch signaling was first identified in Drosophila, where it has been studied in detail at the genetic, molecular, biochemical and cellular levels. In Drosophila, Notch signaling to the nucleus is thought always to be mediated by one specific DNA binding transcription factor, Suppressor of Hairless. In mammals, the homologous genes are called CBF1. All three of the co-repressor proteins have been shown to be necessary for proper gene regulation during Notch signaling in vivo. In mammals, the same general pathway and mechanisms are observed, where CSL proteins are bifunctional DNA binding transcription factors. Thus, CSL is a good example of a bifunctional DNA-binding transcription factor that mediates repression of specific targets genes in one context, but activation of the same targets in another context. This bifunctionality is mediated by the association of specific Co-Repressor complexes vs. specific Co-Activator complexes in different contexts, namely in the absence or presence of Notch signaling. More...
REACT_19241	regulation of_lipid_metabolism_by_peroxisome_proliferator_activated_receptor_alpha	Peroxisome proliferator-activated receptor alpha (PPAR-alpha...... Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma lipid levels. PPAR-alpha is a type II nuclear receptor (its subcellular location does not depend on ligand binding). PPAR-alpha forms heterodimers with Retinoid X receptor alpha (RXR-alpha), another type II nuclear receptor. PPAR-alpha is activated by binding fatty acid ligands, especially polyunsaturated fatty acids having 18-22 carbon groups and 2-6 double bonds. The PPAR-alpha:RXR-alpha heterodimer binds peroxisome proliferator receptor elements (PPREs) in and around target genes. Binding of fatty acids and synthetic ligands causes a conformational change in PPAR-alpha such that it releases the corepressors and binds coactivators (CBP-SRC-HAT complex, ASC complex, and TRAP-Mediator complex) which initiate transcription of the target genes. Target genes of PPAR-alpha participate in fatty acid transport, fatty acid oxidation, triglyceride clearance, lipoprotein production, and cholesterol homeostasis. More...

CREBBP related interactors from protein-protein interaction data in HPRD (count: 199)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
CREBBP	MDC1	No	in vitro;in vivo	16051665
CREBBP	EGR1	Yes	in vivo;yeast 2-hybrid	9806899
CREBBP	HOXA10	No	in vitro;in vivo	11585930
CREBBP	SERTAD2	No	in vivo	16098148
CREBBP	NLK	No	in vitro	14720327
CREBBP	CTNNB1	No	in vivo	11973335
CREBBP	GAK	No	in vitro;yeast 2-hybrid	15752756
CREBBP	FOXO4	No	in vitro;in vivo	10973497
CREBBP	CREBBP	Yes	in vitro;in vivo;yeast 2-hybrid	11463834 , 11259575
CREBBP	KLF5	No	in vitro	12682370
CREBBP	CREM	Yes	in vitro;in vivo	9006899
CREBBP	ALX1	No	in vitro;in vivo;yeast 2-hybrid	12929931
CREBBP	PRKCD	No	in vitro;in vivo	11463380
CREBBP	N4BP2	No	in vivo	12730195
CREBBP	HSF1	No	in vitro;in vivo	14960326
CREBBP	NFIA	No	in vitro	10085123
CREBBP	MGMT	No	in vivo	11564893
CREBBP	STAT4	No	in vitro	14660657
CREBBP	MYB	No	in vitro	12196545
CREBBP	SERTAD3	No	in vivo	16098148
CREBBP	CTBP1	No	in vitro	15834423
CREBBP	PROX1	No	in vivo	11943779
CREBBP	NEUROG1	No	in vivo	11239394
CREBBP	HOXD10	No	in vitro;in vivo	11585930
CREBBP	EBF1	No	in vitro;in vivo	12748286
CREBBP	RPS6KA3	No	in vitro;in vivo	11564891
CREBBP	HOXB1	No	in vitro;in vivo	11585930
CREBBP	EP300	Yes	in vitro	9267036
CREBBP	ZNF639	No	in vivo	16051665
CREBBP	POU2F3	No	in vitro	11429405
CREBBP	SUV39H1	No	in vitro	11252719
CREBBP	KAT2B	No	in vitro;in vivo;yeast 2-hybrid	9445475 , 9267036 , 8684459 , 9687573
CREBBP	JUN	Yes	in vitro;in vivo	9786917 , 2138276 , 16055710
CREBBP	ESR1	Yes	in vitro;in vivo	8616895
CREBBP	RBBP4	No	in vitro;in vivo	10866654
CREBBP	DACH1	No	in vitro	12215533
CREBBP	HTT	No	in vivo;yeast 2-hybrid	11264541 , 10823891
CREBBP	MAML2	No	in vitro	15961999
CREBBP	POU1F1	No	in vitro	9751061
CREBBP	E2F1	No	in vitro;in vivo	8932363
CREBBP	GLI3	No	in vitro;in vivo	10075717
CREBBP	MSH6	No	in vitro;in vivo	16051665
CREBBP	MSH2	Yes	in vitro;in vivo	16051665
CREBBP	RELA	No	in vitro;in vivo;yeast 2-hybrid	9096323 , 9548485
CREBBP	KLF4	Yes	in vitro;in vivo	10666450
CREBBP	ELF3	No	in vitro;in vivo	15075319
CREBBP	RPS6KA5	No	in vitro	12569367
CREBBP	SMAD4	No	in vitro;in vivo	9679056
CREBBP	EID3	No	in vitro;in vivo	15987788
CREBBP	SERTAD1	No	in vitro;in vivo;yeast 2-hybrid	12736710 , 16098148
CREBBP	CHUK	No	in vivo;yeast 2-hybrid	12789342
CREBBP	TP53	No	in vitro;in vivo	11782467 , 10848610 , 9194564
CREBBP	YWHAH	No	in vitro	11266503
CREBBP	ONECUT1	No	in vitro	10811635
CREBBP	MED25	No	in vitro;in vivo;yeast 2-hybrid	17641689
CREBBP	NFIC	No	in vitro	10085123
CREBBP	CENPJ	No	in vitro;in vivo;yeast 2-hybrid	15687488
CREBBP	CEBPD	No	in vitro	12857754
CREBBP	ACTA2	No	in vivo	16051665
CREBBP	ZBTB2	No	in vivo	16051665
CREBBP	SPIB	No	in vitro;in vivo	11864910
CREBBP	FHL2	No	in vitro;in vivo	15572674
CREBBP	SS18L1	No	in vitro	14716005
CREBBP	TRIP10	No	in vitro;yeast 2-hybrid	15752756
CREBBP	MAML1	No	in vitro	12050117
CREBBP	CDH2	No	in vitro	13678586
CREBBP	MLL	No	in vitro	11259575 , 12205094
CREBBP	TCF12	No	in vitro;in vivo	15333839
CREBBP	HNF1B	No	in vitro;in vivo	15509593
CREBBP	RPS6KA1	No	in vitro;in vivo	8756728
CREBBP	HOXB4	No	in vitro;in vivo	11585930
CREBBP	SND1	No	in vitro;in vivo	15695802
CREBBP	SREBF2	No	in vitro;in vivo	8918891
CREBBP	CREB1	Yes	in vitro;in vivo	9413984 , 15073328
CREBBP	MDM2	No	in vitro	9809062
CREBBP	PIAS1	No	yeast 2-hybrid	15957955
CREBBP	EIF2B1	No	in vitro;yeast 2-hybrid	15752756
CREBBP	STAT6	No	in vitro;in vivo	11574547 , 10454341
CREBBP	KAT5	Yes	in vivo	16001085
CREBBP	TGS1	No	in vitro;in vivo	11912212
CREBBP	ETS2	No	in vitro;in vivo	10358095
CREBBP	NPAS2	Yes	in vitro	14645221
CREBBP	NUP98	No	in vitro;in vivo	9858599
CREBBP	CDX2	No	in vitro	19117933
CREBBP	CARM1	No	in vitro;in vivo	12374746
CREBBP	IKBKG	No	in vitro	14597638
CREBBP	MYBL1	No	in vitro	9210395
CREBBP	PELP1	No	in vivo	11481323
CREBBP	CDC25B	No	in vitro	11689696
CREBBP	NKX2-1	No	in vitro	11713256
CREBBP	POLR2A	No	in vitro;in vivo	9710619
CREBBP	HOXD4	No	in vitro;in vivo	11585930
CREBBP	MYC	No	in vitro;in vivo;yeast 2-hybrid	12776737
CREBBP	HOXA11	No	in vitro;in vivo	11585930
CREBBP	SH3GL1	No	in vitro;yeast 2-hybrid	15752756
CREBBP	EWSR1	No	in vitro;in vivo	12459554
CREBBP	KLF13	No	in vitro;in vivo	11748222
CREBBP	GMEB1	No	in vitro	10894151
CREBBP	GCM1	No	in vitro;in vivo	16166624
CREBBP	MAFG	No	in vitro;in vivo	11154691
CREBBP	GATA1	Yes	in vitro	12496368
CREBBP	BRCA1	No	in vivo	10655477
CREBBP	ZBTB17	No	in vitro;yeast 2-hybrid	15752756
CREBBP	NFE2	No	in vitro;in vivo	11154691
CREBBP	SPI1	No	in vitro;yeast 2-hybrid	10050886
CREBBP	THRA	Yes	in vitro;in vivo	8616895
CREBBP	WT1	No	in vitro;in vivo	11278547
CREBBP	HOXB9	No	in vitro;in vivo	11585930
CREBBP	CSNK2A2	No	in vitro	9685505
CREBBP	HLF	No	in vitro	10202154
CREBBP	CITED1	No	in vitro;in vivo	10722728
CREBBP	CALCOCO1	No	in vivo	16931570
CREBBP	SREBF1	No	in vitro	9651391
CREBBP	NAP1L1	No	in vitro	11940655
CREBBP	FGFR1	Yes	in vitro;in vivo	15929978
CREBBP	NCOA6	No	in vivo;yeast 2-hybrid	10866662 , 11158331
CREBBP	HDAC3	No	in vivo	16528103
CREBBP	AP1B1	No	in vitro;yeast 2-hybrid	15752756
CREBBP	CEBPA	No	in vitro	12857754
CREBBP	KAT2A	No	in vitro	9742083
CREBBP	CEBPB	No	in vitro	12857754
CREBBP	CAMK4	No	in vitro;in vivo	11970865
CREBBP	TACC2	No	in vivo	14767476
CREBBP	HNF4A	No	in vitro;yeast 2-hybrid	9434765 , 10085149
CREBBP	HIPK2	No	in vivo	11740489
CREBBP	PHOX2A	No	in vitro	10644760
CREBBP	TRIP4	No	in vitro;yeast 2-hybrid	10454579
CREBBP	HOXB3	No	in vitro;in vivo	11585930
CREBBP	DAXX	No	in vivo	11799127
CREBBP	NFE2L2	No	in vitro;in vivo;yeast 2-hybrid	11683914
CREBBP	PML	No	in vitro;in vivo	10077561 , 12142048 , 12622724 , 10610177 , 12234245
CREBBP	E2F5	No	in vitro;in vivo	10783242
CREBBP	CITED2	No	in vivo	9887100
CREBBP	NCOA1	No	in vitro;in vivo	11003650 , 11113179 , 8616895 , 9445475
CREBBP	PCMT1	No	in vitro;in vivo	11912212
CREBBP	HMGA1	No	yeast 2-hybrid	10428837
CREBBP	SRCAP	No	in vivo;yeast 2-hybrid	10347196 , 11581372
CREBBP	ETS1	No	in vitro;in vivo	9528793
CREBBP	CSNK2A1	No	in vitro	9685505
CREBBP	MBD2	No	in vivo	12665568
CREBBP	CDK5RAP3	No	in vitro;in vivo;yeast 2-hybrid	16012757
CREBBP	MAF	No	in vivo	11943779
CREBBP	NCOA3	No	in vitro	11823864 , 9445475 , 9267036
CREBBP	STAT1	No	in vitro	8986769 , 10848577
CREBBP	GTF2B	No	in vitro	7913207
CREBBP	FOXM1	No	in vitro;in vivo	15024056
CREBBP	TRERF1	No	in vitro;in vivo	11349124
CREBBP	KHDRBS1	No	in vivo	12496368
CREBBP	PAX5	No	in vitro;in vivo;yeast 2-hybrid	11799127
CREBBP	VDR	No	in vitro	10406465
CREBBP	HOXB7	No	in vitro;in vivo	10435624
CREBBP	SMAD2	No	in vitro;in vivo;yeast 2-hybrid	15750622 , 9679056 , 15231748
CREBBP	MYOD1	No	in vitro;in vivo	2176177 , 11463815 , 9238849 , 10944526
CREBBP	MSX1	No	in vivo	10215616 , 11115394
CREBBP	AIRE	No	in vitro;yeast 2-hybrid	10748110
CREBBP	HIF1A	No	in vitro;in vivo;yeast 2-hybrid	10202154 , 17382325 , 11959977 , 16543236
CREBBP	STAT3	No	in vitro;in vivo	15649887
CREBBP	SRF	No	in vitro;in vivo	9388250
CREBBP	NCOA2	No	in vitro;yeast 2-hybrid	9430642
CREBBP	NFATC2	No	in vitro	9625762
CREBBP	TP73	No	in vitro	11279015
CREBBP	SNIP1	No	in vitro;in vivo	10887155
CREBBP	FOXO1	No	in vivo	10973497
CREBBP	STAT2	No	in vitro;in vivo	8848048 , 10464260
CREBBP	HDAC1	No	in vivo	16528103
CREBBP	SMAD3	No	in vitro;in vivo	15750622
CREBBP	MECOM	No	in vitro;in vivo	11568182
CREBBP	MYBL2	No	in vitro;in vivo	11423988
CREBBP	H3F3A	No	in vitro	15616580
CREBBP	SOX9	No	in vitro;in vivo	12732631
CREBBP	UBTF	No	in vitro;in vivo	11106745
CREBBP	IRF3	No	in vitro;in vivo	10521456 , 12473110
CREBBP	RXRG	No	in vitro;in vivo;yeast 2-hybrid	8616895
CREBBP	IRF7	No	in vitro	12604599
CREBBP	PTMA	No	in vitro;in vivo	11897665
CREBBP	HOXB2	No	in vitro;in vivo	11585930
CREBBP	ACVR1	No	in vitro	9267036
CREBBP	KPNA2	No	in vitro;in vivo	10801418
CREBBP	CSK	No	in vivo	10801129
CREBBP	BCL3	No	in vitro	10497212
CREBBP	GABPA	No	in vitro	9990060
CREBBP	HOXB6	No	in vitro;in vivo	11585930
CREBBP	AR	Yes	in vitro;in vivo	9482849 , 9822653
CREBBP	NPAT	No	in vitro;in vivo	15555599
CREBBP	HNF1A	No	in vitro;in vivo	10777539
CREBBP	NR3C1	Yes	in vitro	9649342
CREBBP	CRX	No	in vitro;in vivo	10708567
CREBBP	JDP2	No	in vitro	12101239
CREBBP	ELK1	No	in vitro;in vivo	8941362
CREBBP	DDX5	No	in vitro;in vivo	12527917
CREBBP	GMEB2	No	in vitro	10894151
CREBBP	CUX1	No	in vitro;in vivo	10852958
CREBBP	ATF1	No	in vitro;in vivo	8663317
CREBBP	RBCK1	No	in vitro;in vivo	15833741
CREBBP	NFATC4	No	in vitro;in vivo	11514544
CREBBP	TDG	No	in vitro;in vivo;yeast 2-hybrid	11864601
CREBBP	CNOT3	No	in vitro;yeast 2-hybrid	15752756
CREBBP	HOXA9	No	in vitro	15161102
CREBBP	TCF3	No	in vitro;in vivo;yeast 2-hybrid	12435739 , 15507449

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Literature-origin BioCarta pathway

Gene mapped BioCarta pathways

Gene mapped Reactome pathways