
Gene Report
Approved Symbol | YWHAE |
---|---|
Approved Name | tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide |
Symbol Alias | FLJ45465 |
Name Alias | 14-3-3 epsilon |
Location | 17p13.3 |
Position | chr17:1247834-1303556 (-) |
External Links |
Entrez Gene: 7531 Ensembl: ENSG00000108953 UCSC: uc002fsj.3 HGNC ID: 12851 |
No. of Studies (Positive/Negative) | 1(0/1)
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Type | Literature-origin |
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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 |
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Name in Literature | Reference | Research Type | Statistical Result | Relation Description |
---|---|---|---|---|
YWHAE | Liu J, 2011 | Patients and nomal controls | No association was found with schizophrenia, major depressiv...... No association was found with schizophrenia, major depressive disorder or bipolar disorder. More... |
Approved Name | UniportKB | No. of Studies (Positive/Negative) | Source | |
---|---|---|---|---|
14-3-3 protein epsilon | P62258 | 0(0/0) | Gene mapped |
Literature-origin GO terms | ||||
ID | Name | Type | Evidence | |
---|---|---|---|---|
GO:0006915 | apoptotic process | biological process | TAS |
Gene mapped GO terms | ||||
ID | Name | Type | Evidence | |
---|---|---|---|---|
GO:0021987 | cerebral cortex development | biological process | IEA | |
GO:0019048 | virus-host interaction | biological process | IEA | |
GO:0032403 | protein complex binding | molecular function | IEA | |
GO:0006605 | protein targeting | biological process | IEA | |
GO:0042470 | melanosome | cellular component | IEA | |
GO:0001764 | neuron migration | biological process | IEA | |
GO:0005871 | kinesin complex | cellular component | IEA | |
GO:0033267 | axon part | cellular component | IEA | |
GO:0051219 | phosphoprotein binding | molecular function | IPI[10869435] | |
GO:0050815 | phosphoserine binding | molecular function | IPI[10869435] | |
GO:0035308 | negative regulation of protein dephosphorylation | biological process | IEA | |
GO:0000278 | mitotic cell cycle | biological process | TAS | |
GO:0042826 | histone deacetylase binding | molecular function | IPI[10869435] | |
GO:0019899 | enzyme binding | molecular function | IPI[10788521] | |
GO:0019904 | protein domain specific binding | molecular function | IEA | |
GO:0048011 | nerve growth factor receptor signaling pathway | biological process | TAS | |
GO:0005829 | cytosol | cellular component | TAS | |
GO:0000086 | G2/M transition of mitotic cell cycle | biological process | TAS | |
GO:0021766 | hippocampus development | biological process | IEA | |
GO:0035556 | intracellular signal transduction | biological process | TAS[7644510] | |
GO:0035329 | hippo signaling cascade | biological process | TAS | |
GO:0005739 | mitochondrion | cellular component | IEA | |
GO:0005515 | protein binding | molecular function | IPI |
Gene mapped KEGG pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
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... | |
hsa04722 | neurotrophin signaling_pathway | Neurotrophin signaling pathway | Neurotrophins are a family of trophic factors involved in di...... Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory. More... | |
hsa04114 | oocyte meiosis | Oocyte meiosis | During meiosis, a single round of DNA replication is followe...... During meiosis, a single round of DNA replication is followed by two rounds of chromosome segregation, called meiosis I and meiosis II. At meiosis I, homologous chromosomes recombine and then segregate to opposite poles, while the sister chromatids segregate from each other at meoisis II. In vertebrates, immature oocytes are arrested at the PI (prophase of meiosis I). The resumption of meiosis is stimulated by progesterone, which carries the oocyte through two consecutive M-phases (MI and MII) to a second arrest at MII. The key activity driving meiotic progression is the MPF (maturation-promoting factor), a heterodimer of CDC2 (cell division cycle 2 kinase) and cyclin B. In PI-arrested oocytes, MPF is initially inactive and is activated by the dual-specificity CDC25C phosphatase as the result of new synthesis of Mos induced by progesterone. MPF activation mediates the transition from the PI arrest to MI. The subsequent decrease in MPF levels, required to exit from MI into interkinesis, is induced by a negative feedback loop, where CDC2 brings about the activation of the APC (anaphase-promoting complex), which mediates destruction of cyclin B. Re-activation of MPF for MII requires re-accumulation of high levels of cyclin B as well as the inactivation of the APC by newly synthesized Emi2 and other components of the CSF (cytostatic factor), such as cyclin E or high levels of Mos. CSF antagonizes the ubiquitin ligase activity of the APC, preventing cyclin B destruction and meiotic exit until fertilization occurs. Fertilization triggers a transient increase in cytosolic free Ca2+, which leads to CSF inactivation and cyclin B destruction through the APC. Then eggs are released from MII into the first embryonic cell cycle. More... |
Gene mapped BioCarta pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
CHREBP2_PATHWAY | chrebp2 pathway | Regulation And Function Of ChREBP in Liver | Liver is the major site for carbohydrate metabolism (glycoly...... Liver is the major site for carbohydrate metabolism (glycolysis and glycogen synthesis) and triglyceride synthesis (lipogenesis). While insulin was long thought to be the major regulator of hepatic gene expression, emerging evidence show that nutrients, in particular, glucose and fatty acids, are also able to regulate hepatic genes. This diagram illustrates how glucose metabolite, rather than glucose itself, contributes to the coordinated regulation of carbohydrate and lipid homeostasis in liver through phosphorylation-dependent regulation of ChREBP (carbohydrate responsive element binding protein). ChREBP is a basic helix-loop helix/leucine zipper (bHLH/LZ) transcription factor, shuttling between the cytoplasm and nucleus in a glucose-responsive manner in hepatocytes. When serum glucose is elevated, glucose transporter (GLUT2) and glucokinase (GCK) allow for rapid uptake and equilibration of intracellular glucose levels. This flux of glucose promotes, via the hexose monophosphate shunt pathway (HMP Shunt), the formation of xylulose-5-phosphate (Xu-5-P), which activates protein phosphatase 2A (PP2A) to dephosphorylate ChREBP (Ser196) and promote its nuclear localization. PP2A further dephosphorylates ChREBP in the nucleus, allowing it to dimerize with the bHLH/LZ transcription factor Max-like protein X (MLX) and activate transcription of a number of glycolytic and lipogenic genes containing a ChoRE, such as liver-type pyruvate kinase (L-PK), acetyl-CoA carboxylase 1 (ACACA), and fatty acid synthase (FASN). Upon starvation or high-fat feeding, intrahepatic levels of cAMP and AMP are elevated to activate protein kinase A (PKA) and AMP-dependent protein kinase (AMPK), respectively. PKA-mediated phosphorylation of Thr666 and Ser626 inhibits the DNA binding capacity of ChREBP; so does AMPK-mediated modification of Ser568. PKA-dependent phosphorylation of Ser196 promotes interaction with 14-3-3 and thus sequesters ChREBP in the cytosol. In summary, the phosphorylated form of ChREBP is rendered inactive due to its diminished DNA binding capacity and subcellular compartmentalization. Glucose metabolism triggers dephosphorylation of ChREBP, allowing it to enter the nucleus and activate the transcription of both glycolytic and lipogenic gene expression in liver. The fact that ChREBP/ mice are intolerant to glucose and insulin resistant suggests that ChREBP may also play a role in the pathogenesis of type 2 diabetes. More... |
Gene mapped Reactome pathways | |||
ID | Name | Description | |
---|---|---|---|
REACT_13776 | p75 ntr_receptor_mediated_signalling | Besides signalling through the tyrosine kinase receptors TRK...... Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated. A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus , while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways. More... | |
REACT_15364 | loss of_nlp_from_mitotic_centrosomes | During interphase, Nlp interacts with gamma-tubulin ring com...... During interphase, Nlp interacts with gamma-tubulin ring complexes. Plk1 is activated at the onset of mitosis and phosphorylates Nlp triggering its displacement from the centrosome. Removal of Nlp appears to contribute to the establishment of a mitotic scaffold with enhanced microtubule nucleation activity. More... | |
REACT_15479 | centrosome maturation | The centrosome is the primary microtubule organizing center. The centrosome is the primary microtubule organizing center. | |
REACT_152 | cell cycle_mitotic | The replication of the genome and the subsequent segregation...... The replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried out during a discrete temporal period known as the S (synthesis)-phase, and chromosome segregation occurs during a massive reorganization to cellular architecture at mitosis. Two gap-phases separate these major cell cycle events: G1 between mitosis and S-phase, and G2 between S-phase and mitosis. In the development of the human body, cells can exit the cell cycle for a period and enter a quiescent state known as G0, or terminally differentiate into cells that will not divide again, but undergo morphological development to carry out the wide variety of specialized functions of individual tissues. A family of protein serine/threonine kinases known as the cyclin-dependent kinases (CDKs) controls progression through the cell cycle. As the name suggests, the activity of the catalytic subunit is dependent on binding to a cyclin partner. The human genome encodes several cyclins and several CDKs, with their names largely derived from the order in which they were identified. The oscillation of cyclin abundance is one important mechanism by which these enzymes phosphorylate key substrates to promote events at the relevant time and place. Additional regulatory proteins and post-translational modifications ensure that CDK activity is precisely regulated, frequently confined to a narrow window of activity. More... | |
REACT_2203 | g2 m_transition | Cyclin A can also form complexes with Cdc2 (Cdk1). Together ...... Cyclin A can also form complexes with Cdc2 (Cdk1). Together with three B-type cyclins, Cdc2 (Cdk1) regulates the transition from G2 into mitosis. These complexes are activated by dephosphorylation of T14 and Y15. Cyclin A, B - Cdc2 complexes phosphorylate several proteins involved in mitotic spindle structure and function, the breakdown of the nuclear envelope, and topological changes in chromosomes allowing resolution of their entanglement and condensation that is necessary for the ~2 meters of DNA to be segregated at mitosis. More... | |
REACT_13720 | cell death_signalling_via_nrage_nrif_and_nade | p75NTR is a key regulator of neuronal apoptosis, both during...... p75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNGF is at least 10 times more potent than mature NGF in inducing apoptosis. TRKA signalling protects neurons from apoptosis. The molecular mechanisms involved in p75NTR-apoptosis are not well understood. The death signalling requires activation of c-JUN N-terminal Kinase (JNK), as well as transcriptional events. JNK activation appears to involve the receptor interacting proteins TRAF6, NRAGE, and Rac. The transcription events are thought to be regulated by another p75-interacting protein, NRIF. Two other p75-interacting proteins, NADE and Necdin, have been implicated in apoptosis, but their role is less clear. More... | |
REACT_11061 | signalling by_ngf | Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles i...... Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling. More... |

Gene | Interactor | Interactor in MK4MDD? | Experiment Type | PMID | |
---|---|---|---|---|---|
YWHAE | CDK14 | No | yeast 2-hybrid | 16775625 | |
YWHAE | MAP3K10 | No | yeast 2-hybrid | 9427749 | |
YWHAE | CDC25B | No | in vitro;in vivo | 10713667 , 7644510 | |
YWHAE | TOP2A | No | in vivo | 10788521 | |
YWHAE | IRS1 | No | in vivo | 9312143 , 9111084 | |
YWHAE | GPRIN2 | No | yeast 2-hybrid | 16189514 | |
YWHAE | AKAP13 | No | in vitro;in vivo | 15229649 | |
YWHAE | CDC25A | No | in vitro;in vivo;yeast 2-hybrid | 7644510 , 14559997 | |
YWHAE | RIN1 | No | in vitro;in vivo | 11784866 , 9144171 | |
YWHAE | SLC8A1 | No | in vitro | 16679322 | |
YWHAE | SLC8A2 | No | in vivo;yeast 2-hybrid | 16679322 | |
YWHAE | ING1 | No | in vitro | 16581770 | |
YWHAE | MAP3K2 | No | in vivo | 9452471 | |
YWHAE | KCNH2 | No | in vitro;in vivo;yeast 2-hybrid | 11953308 | |
YWHAE | MAP3K5 | No | yeast 2-hybrid | 15023544 | |
YWHAE | HDAC4 | No | in vitro;in vivo;yeast 2-hybrid | 11486037 , 11114197 | |
YWHAE | KCNK9 | No | in vivo;yeast 2-hybrid | 12433946 | |
YWHAE | KCNK3 | No | in vivo;yeast 2-hybrid | 12433946 | |
YWHAE | CDK11B | No | in vitro;in vivo | 15883043 | |
YWHAE | NCOR2 | No | in vitro | 15494311 | |
YWHAE | SNCA | No | in vivo | 10407019 | |
YWHAE | RASGRF1 | Yes | in vitro;in vivo;yeast 2-hybrid | 11533041 | |
YWHAE | BAD | No | yeast 2-hybrid | 9369453 | |
YWHAE | DYRK1A | No | in vitro;in vivo | 15369779 | |
YWHAE | IRS2 | No | in vivo | 9312143 | |
YWHAE | ARHGEF2 | Yes | in vivo | 14970201 | |
YWHAE | MDM4 | No | in vivo | 16511560 , 16511572 | |
YWHAE | YWHAH | No | in vivo | 7615088 , 12507503 | |
YWHAE | TSC1 | No | in vitro | 12176984 | |
YWHAE | HSF1 | No | in vitro | 15364926 | |
YWHAE | MAP3K3 | No | in vitro;yeast 2-hybrid | 9452471 , 16407301 | |
YWHAE | RAF1 | No | in vitro;in vivo | 7644510 , 8702721 , 15459208 | |
YWHAE | MST1R | No | in vitro;in vivo;yeast 2-hybrid | 12919677 | |
YWHAE | HDAC5 | Yes | in vitro;in vivo;yeast 2-hybrid | 10869435 , 11114197 | |
YWHAE | RPGR | No | in vivo | 16043481 | |
YWHAE | IGF1R | No | in vitro;yeast 2-hybrid | 9111084 | |
YWHAE | ATXN1 | No | in vitro;in vivo;yeast 2-hybrid | 12757707 | |
YWHAE | KIF1C | No | in vivo | 10559254 | |
YWHAE | REM1 | No | in vitro;in vivo | 10441394 | |
YWHAE | SRC | No | in vivo | 8702721 | |
YWHAE | SLC8A3 | No | in vitro | 16679322 | |
YWHAE | VIM | Yes | in vitro;in vivo | 10887173 | |
YWHAE | WWTR1 | No | in vivo | 11118213 | |
YWHAE | TBP | No | in vitro | 10449590 | |
YWHAE | CDK16 | No | in vivo | 12154078 | |
YWHAE | YWHAZ | No | in vivo | 16376338 | |
YWHAE | PRKCG | No | in vitro;in vivo | 15459208 | |
YWHAE | NGFRAP1 | No | in vitro;in vivo;yeast 2-hybrid | 11278287 | |
YWHAE | SORBS2 | Yes | yeast 2-hybrid | 16189514 | |
YWHAE | TNFAIP3 | No | in vivo | 8702721 | |
YWHAE | ABL1 | No | in vivo | 15696159 | |
YWHAE | YWHAG | No | in vitro | 12507503 | |
YWHAE | KRT18 | No | in vivo | 9524113 | |
YWHAE | TAF7 | No | in vitro | 10449590 | |
YWHAE | KCNK15 | No | in vivo;yeast 2-hybrid | 12433946 | |
YWHAE | TFDP2 | No | in vitro;in vivo;yeast 2-hybrid | 16482218 | |
YWHAE | CALM1 | No | in vitro;yeast 2-hybrid | 10088721 | |
YWHAE | RGS3 | No | in vivo | 11985497 | |
YWHAE | GTF2B | No | in vitro | 10449590 | |
YWHAE | GRAP2 | No | yeast 2-hybrid | 16189514 | |
YWHAE | CDKN1B | No | in vivo | 12042314 | |
YWHAE | TSC2 | No | in vitro | 12438239 | |
YWHAE | CASP3 | No | in vitro;yeast 2-hybrid | 12657644 | |
YWHAE | YWHAB | No | in vivo | 12507503 | |
YWHAE | TGFB1 | No | in vivo | 11172812 | |
YWHAE | NDEL1 | No | in vitro;in vivo;yeast 2-hybrid | 12796778 | |
YWHAE | BCR | No | in vivo | 16045749 | |
YWHAE | PAPOLA | No | in vitro;in vivo;yeast 2-hybrid | 14517258 | |
YWHAE | TAZ | No | in vivo | 11118213 |