View source for YWHAE

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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''14-3-3 protein epsilon''' is a [[protein]] that in humans is encoded by the ''YWHAE'' [[gene]].<ref name="pmid9371399">{{cite journal | vauthors = Luk SC, Garcia-Barcelo M, Tsui SK, Fung KP, Lee CY, Waye MM | title = Assignment of the human 14-3-3 epsilon isoform (YWHAE) to human chromosome 17p13 by in situ hybridization | journal = Cytogenet Cell Genet | volume = 78 | issue = 2 | pages = 105–6 | date = December 1997 | pmid = 9371399 | doi = 10.1159/000134638 }}</ref>
== Function ==
This gene product belongs to the [[14-3-3]] family of proteins which mediate [[signal transduction]] by binding to [[phosphoserine]]-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, [[RAF1]] and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of [[insulin sensitivity]]. It has also been implicated in the pathogenesis of [[small cell lung cancer]],<ref>{{cite web | title = Entrez Gene: YWHAE tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7531}}</ref> and microdeletions associated with [[Miller–Dieker syndrome]].<ref name="pmid29628935">{{cite journal | vauthors = Blazejewski SM, Bennison SA, Smith TH, Toyo-Oka K | title = Neurodevelopmental Genetic Diseases Associated With Microdeletions and Microduplications of Chromosome 17p13.3 | journal = Frontiers in Genetics | volume = 9 | pages = 80 | date = 2018 | pmid = 29628935 | pmc = 5876250 | doi = 10.3389/fgene.2018.00080 | doi-access = free }}</ref>
== Interactions ==
YWHAE has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[C-Raf]],<ref name = pmid7644510/><ref name = pmid8702721>{{cite journal | vauthors = Vincenz C, Dixit VM | title = 14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 20029–34 | date = August 1996 | pmid = 8702721 | doi =  10.1074/jbc.271.33.20029| doi-access = free }}</ref>
* [[CDC25B]],<ref name = pmid10713667>{{cite journal | vauthors = Mils V, Baldin V, Goubin F, Pinta I, Papin C, Waye M, Eychene A, Ducommun B | title = Specific interaction between 14-3-3 isoforms and the human CDC25B phosphatase | journal = Oncogene | volume = 19 | issue = 10 | pages = 1257–65 | date = March 2000 | pmid = 10713667 | doi = 10.1038/sj.onc.1203419 | doi-access = free }}</ref><ref name = pmid7644510>{{cite journal | vauthors = Conklin DS, Galaktionov K, Beach D | title = 14-3-3 proteins associate with cdc25 phosphatases | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 17 | pages = 7892–6 | date = August 1995 | pmid = 7644510 | pmc = 41252 | doi =  10.1073/pnas.92.17.7892| bibcode = 1995PNAS...92.7892C | doi-access = free }}</ref>
* [[HDAC4]],<ref name = pmid11504882>{{cite journal | vauthors = Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T | title = Differential localization of HDAC4 orchestrates muscle differentiation | journal = Nucleic Acids Res. | volume = 29 | issue = 16 | pages = 3439–47 | date = August 2001 | pmid = 11504882 | pmc = 55849 | doi =  10.1093/nar/29.16.3439}}</ref><ref name = pmid10869435>{{cite journal | vauthors = Grozinger CM, Schreiber SL | title = Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 14 | pages = 7835–40 | date = July 2000 | pmid = 10869435 | pmc = 16631 | doi = 10.1073/pnas.140199597 | bibcode = 2000PNAS...97.7835G | doi-access = free }}</ref>
* [[HERG]],<ref name = pmid11953308>{{cite journal | vauthors = Kagan A, Melman YF, Krumerman A, McDonald TV | title = 14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity | journal = EMBO J. | volume = 21 | issue = 8 | pages = 1889–98 | date = April 2002 | pmid = 11953308 | pmc = 125975 | doi = 10.1093/emboj/21.8.1889 }}</ref>
* [[IRS1]]<ref name = pmid9111084/> and
* [[Insulin-like growth factor 1 receptor|IGF1R]],<ref name = pmid9111084>{{cite journal | vauthors = Craparo A, Freund R, Gustafson TA | title = 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner | journal = J. Biol. Chem. | volume = 272 | issue = 17 | pages = 11663–9 | date = April 1997 | pmid = 9111084 | doi =  10.1074/jbc.272.17.11663| doi-access = free }}</ref>
* [[MAP3K3]],<ref name = pmid9452471>{{cite journal | vauthors = Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR | title = 14-3-3 proteins interact with specific MEK kinases | journal = J. Biol. Chem. | volume = 273 | issue = 6 | pages = 3476–83 | date = February 1998 | pmid = 9452471 | doi =  10.1074/jbc.273.6.3476| doi-access = free }}</ref>
* [[NDEL1]],<ref name = pmid12796778>{{cite journal | vauthors = Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A | title = 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome | journal = Nat. Genet. | volume = 34 | issue = 3 | pages = 274–85 | date = July 2003 | pmid = 12796778 | doi = 10.1038/ng1169 | s2cid = 10301633 }}</ref>
* [[NGFRAP1]],<ref name = pmid11278287>{{cite journal | vauthors = Kimura MT, Irie S, Shoji-Hoshino S, Mukai J, Nadano D, Oshimura M, Sato TA | title = 14-3-3 is involved in p75 neurotrophin receptor-mediated signal transduction | journal = J. Biol. Chem. | volume = 276 | issue = 20 | pages = 17291–300 | date = May 2001 | pmid = 11278287 | doi = 10.1074/jbc.M005453200 | doi-access = free }}</ref>  and
* [[TGF beta 1]].<ref name = pmid11172812>{{cite journal | vauthors = McGonigle S, Beall MJ, Feeney EL, Pearce EJ | title = Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors | journal = FEBS Lett. | volume = 490 | issue = 1–2 | pages = 65–9 | date = February 2001 | pmid = 11172812 | doi =  10.1016/S0014-5793(01)02133-0| s2cid = 84710903 | doi-access =  }}</ref>
{{Div col end}}
==See also==
* [[14-3-3 protein]]
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
*{{cite journal | vauthors = Kino T, Pavlakis GN | title = Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1 | journal = DNA Cell Biol. | volume = 23 | issue = 4 | pages = 193–205 | year = 2004 | pmid = 15142377 | doi = 10.1089/104454904773819789 | url = https://zenodo.org/record/1235217 }}
*{{cite journal | vauthors = Kino T, Chrousos GP | title = Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome? | journal = Ann. N. Y. Acad. Sci. | volume = 1024 | pages = 153–67 | year = 2004 | issue = 1 | pmid = 15265780 | doi = 10.1196/annals.1321.013 | bibcode = 2004NYASA1024..153K | s2cid = 23655886 | url = https://zenodo.org/record/1235880 }}
*{{cite journal | vauthors = Jones DH, Ley S, Aitken A | title = Isoforms of 14-3-3 protein can form homo- and heterodimers in vivo and in vitro: implications for function as adapter proteins | journal = FEBS Lett. | volume = 368 | issue = 1 | pages = 55–8 | year = 1995 | pmid = 7615088 | doi = 10.1016/0014-5793(95)00598-4 | s2cid = 7233378 | doi-access =  }}
*{{cite journal | vauthors = Conklin DS, Galaktionov K, Beach D | title = 14-3-3 proteins associate with cdc25 phosphatases | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 17 | pages = 7892–6 | year = 1995 | pmid = 7644510 | pmc = 41252 | doi = 10.1073/pnas.92.17.7892 | bibcode = 1995PNAS...92.7892C | doi-access = free }}
*{{cite journal | vauthors = Jin DY, Lyu MS, Kozak CA, Jeang KT | title = Function of 14-3-3 proteins | journal = Nature | volume = 382 | issue = 6589 | pages = 308 | year = 1996 | pmid = 8684458 | doi = 10.1038/382308a0 | bibcode = 1996Natur.382..308J | s2cid = 7296682 | url = https://zenodo.org/record/1233186 | doi-access = free }}
*{{cite journal | vauthors = Vincenz C, Dixit VM | title = 14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 20029–34 | year = 1996 | pmid = 8702721 | doi = 10.1074/jbc.271.33.20029 | doi-access = free }}
*{{cite journal | vauthors = Chong SS, Tanigami A, Roschke AV, Ledbetter DH | title = 14-3-3 epsilon has no homology to LIS1 and lies telomeric to it on chromosome 17p13.3 outside the Miller-Dieker syndrome chromosome region | journal = Genome Res. | volume = 6 | issue = 8 | pages = 735–41 | year = 1997 | pmid = 8858348 | doi = 10.1101/gr.6.8.735 | doi-access = free }}
*{{cite journal | vauthors = Craparo A, Freund R, Gustafson TA | title = 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner | journal = J. Biol. Chem. | volume = 272 | issue = 17 | pages = 11663–9 | year = 1997 | pmid = 9111084 | doi = 10.1074/jbc.272.17.11663 | doi-access = free }}
*{{cite journal | vauthors = Han L, Wong D, Dhaka A, Afar D, White M, Xie W, Herschman H, Witte O, Colicelli J | title = Protein binding and signaling properties of RIN1 suggest a unique effector function | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 10 | pages = 4954–9 | year = 1997 | pmid = 9144171 | pmc = 24612 | doi = 10.1073/pnas.94.10.4954 | bibcode = 1997PNAS...94.4954H | doi-access = free }}
*{{cite journal | vauthors = Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi M, Yazaki Y, Oka Y, Asano T | title = 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain | journal = J. Biol. Chem. | volume = 272 | issue = 40 | pages = 25267–74 | year = 1997 | pmid = 9312143 | doi = 10.1074/jbc.272.40.25267 | doi-access =  free}}
*{{cite journal | vauthors = Hsu SY, Kaipia A, Zhu L, Hsueh AJ | title = Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11 | journal = Mol. Endocrinol. | volume = 11 | issue = 12 | pages = 1858–67 | year = 1997 | doi = 10.1210/mend.11.12.0023 | pmid = 9369453 | doi-access = free }}
*{{cite journal | vauthors = ((Nagata Ki)), Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T, Hirokawa N, Hall A | title = The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3 | journal = EMBO J. | volume = 17 | issue = 1 | pages = 149–58 | year = 1998 | pmid = 9427749 | pmc = 1170366 | doi = 10.1093/emboj/17.1.149 }}
*{{cite journal | vauthors = Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR | title = 14-3-3 proteins interact with specific MEK kinases | journal = J. Biol. Chem. | volume = 273 | issue = 6 | pages = 3476–83 | year = 1998 | pmid = 9452471 | doi = 10.1074/jbc.273.6.3476 | doi-access = free }}
*{{cite journal | vauthors = Ku NO, Liao J, Omary MB | title = Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3 proteins | journal = EMBO J. | volume = 17 | issue = 7 | pages = 1892–906 | year = 1998 | pmid = 9524113 | pmc = 1170536 | doi = 10.1093/emboj/17.7.1892 }}
*{{cite journal | vauthors = Luk SC, Ngai SM, Tsui SK, Fung KP, Lee CY, Waye MM | title = In vivo and in vitro association of 14-3-3 epsilon isoform with calmodulin: implication for signal transduction and cell proliferation | journal = J. Cell. Biochem. | volume = 73 | issue = 1 | pages = 31–5 | year = 1999 | pmid = 10088721 | doi = 10.1002/(SICI)1097-4644(19990401)73:1<31::AID-JCB4>3.0.CO;2-X | s2cid = 1160678 }}
*{{cite journal | vauthors = Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B | author7-link=Benjamin Wolozin | title = alpha-Synuclein shares physical and functional homology with 14-3-3 proteins | journal = J. Neurosci. | volume = 19 | issue = 14 | pages = 5782–91 | year = 1999 | pmid = 10407019 | doi =  10.1523/JNEUROSCI.19-14-05782.1999| pmc=6783081 | doi-access = free }}
*{{cite journal | vauthors = Finlin BS, Andres DA | title = Phosphorylation-dependent association of the Ras-related GTP-binding protein Rem with 14-3-3 proteins | journal = Arch. Biochem. Biophys. | volume = 368 | issue = 2 | pages = 401–12 | year = 1999 | pmid = 10441394 | doi = 10.1006/abbi.1999.1316 }}
*{{cite journal | vauthors = Dorner C, Ullrich A, Häring HU, Lammers R | title = The kinesin-like motor protein KIF1C occurs in intact cells as a dimer and associates with proteins of the 14-3-3 family | journal = J. Biol. Chem. | volume = 274 | issue = 47 | pages = 33654–60 | year = 1999 | pmid = 10559254 | doi = 10.1074/jbc.274.47.33654 | doi-access = free }}
*{{cite journal | vauthors = Aoki H, Hayashi J, Moriyama M, Arakawa Y, Hino O | title = Hepatitis C Virus Core Protein Interacts with 14-3-3 Protein and Activates the Kinase Raf-1 | journal = J. Virol. | volume = 74 | issue = 4 | pages = 1736–41 | year = 2000 | pmid = 10644344 | pmc = 111649 | doi = 10.1128/JVI.74.4.1736-1741.2000 }}
{{refend}}
{{PDB Gallery|geneid=7531}}
{{Adaptor proteins}}
[[Category:14-3-3 proteins]]