Gene Report

Basic Information

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)
Type	Literature-origin

Positive relationships between YWHAE and MDD (count: 0)

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

Positive relationship network of YWHAE 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 YWHAE and MDD (count: 1)

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...

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

YWHAE related SNPs in MK4MDD (count: 0)

YWHAE related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
14-3-3 protein epsilon	P62258	0(0/0)	Gene mapped

YWHAE related GO terms (count: 24)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006915	apoptotic process	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
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

YWHAE related KEGG pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
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...

YWHAE related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
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...

YWHAE related Reactome pathways (count: 7)

ID	Name	Description
Gene mapped Reactome pathways
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...

YWHAE related interactors from protein-protein interaction data in HPRD (count: 69)

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

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways