YWHAH

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta
PDB rendering based on 2c63.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2C63​, 2C74​
Identifiers
Symbols	YWHAH ; YWHA1
External IDs	OMIM: 113508 MGI: 109194 HomoloGene: 37767 GeneCards: YWHAH Gene
Gene ontology Molecular function • actin binding • insulin-like growth factor receptor binding • protein binding • sodium channel regulator activity • enzyme binding • protein domain specific binding • glucocorticoid receptor binding • ion channel binding • protein heterodimerization activity Cellular component • cytoplasm • cytosol • plasma membrane • intercalated disc • cytoplasmic vesicle membrane • extracellular exosome Biological process • regulation of sodium ion transport • transcription initiation from RNA polymerase II promoter • glucocorticoid catabolic process • intracellular protein transport • apoptotic process • small GTPase mediated signal transduction • gene expression • programmed cell death • substantia nigra development • glucocorticoid receptor signaling pathway • regulation of neuron differentiation • positive regulation of transcription, DNA-templated • regulation of synaptic plasticity • negative regulation of dendrite morphogenesis • membrane organization • membrane depolarization during action potential • intrinsic apoptotic signaling pathway • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • regulation of sodium ion transmembrane transporter activity Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7533	22629
Ensembl	ENSG00000128245	ENSMUSG00000018965
UniProt	Q04917	P68510
RefSeq (mRNA)	NM_003405	NM_011738
RefSeq (protein)	NP_003396	NP_035868
Location (UCSC)	Chr 22: 31.94 – 31.96 Mb	Chr 5: 33.02 – 33.03 Mb
PubMed search

14-3-3 protein eta is a protein that in humans is encoded by the YWHAH gene.

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 99% identical to the mouse, rat and bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat has been associated with early-onset schizophrenia.^[1]

Interactions

YWHAH has been shown to interact with:

• C-Raf,^[2][3][4]
• CDC25B,^[5]
• EPB41L3,^[6]
• Glucocorticoid receptor,^[7]
• KIF5B,^[3]
• KLC3,^[3]
• Phosphoinositide-dependent kinase-1,^[8]
• RIMS1,^[9]
• RIMS2,^[9]
• TLX2,^[10]
• TNFAIP3,^[2][11] and
• ZFP36.^[12]

References

1. "Entrez Gene: YWHAH tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide".
2. Vincenz C, Dixit VM (Aug 1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". The Journal of Biological Chemistry 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. PMID 8702721.
3. Ichimura T, Wakamiya-Tsuruta A, Itagaki C, Taoka M, Hayano T, Natsume T, Isobe T (Apr 2002). "Phosphorylation-dependent interaction of kinesin light chain 2 and the 14-3-3 protein". Biochemistry 41 (17): 5566–72. doi:10.1021/bi015946f. PMID 11969417.
4. Van Der Hoeven PC, Van Der Wal JC, Ruurs P, Van Dijk MC, Van Blitterswijk J (Jan 2000). "14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation". The Biochemical Journal 345 (2): 297–306. doi:10.1042/bj3450297. PMC 1220759. PMID 10620507.
5. Mils V, Baldin V, Goubin F, Pinta I, Papin C, Waye M, Eychene A, Ducommun B (Mar 2000). "Specific interaction between 14-3-3 isoforms and the human CDC25B phosphatase". Oncogene 19 (10): 1257–65. doi:10.1038/sj.onc.1203419. PMID 10713667.
6. Yu T, Robb VA, Singh V, Gutmann DH, Newsham IF (Aug 2002). "The 4.1/ezrin/radixin/moesin domain of the DAL-1/Protein 4.1B tumour suppressor interacts with 14-3-3 proteins". The Biochemical Journal 365 (Pt 3): 783–9. doi:10.1042/BJ20020060. PMC 1222735. PMID 11996670.
7. Wakui H, Wright AP, Gustafsson J, Zilliacus J (Mar 1997). "Interaction of the ligand-activated glucocorticoid receptor with the 14-3-3 eta protein". The Journal of Biological Chemistry 272 (13): 8153–6. doi:10.1074/jbc.272.13.8153. PMID 9079630.
8. Sato S, Fujita N, Tsuruo T (Oct 2002). "Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3". The Journal of Biological Chemistry 277 (42): 39360–7. doi:10.1074/jbc.M205141200. PMID 12177059.
9. Sun L, Bittner MA, Holz RW (Oct 2003). "Rim, a component of the presynaptic active zone and modulator of exocytosis, binds 14-3-3 through its N terminus". The Journal of Biological Chemistry 278 (40): 38301–9. doi:10.1074/jbc.M212801200. PMID 12871946.
10. Tang SJ, Suen TC, McInnes RR, Buchwald M (Sep 1998). "Association of the TLX-2 homeodomain and 14-3-3eta signaling proteins". The Journal of Biological Chemistry 273 (39): 25356–63. doi:10.1074/jbc.273.39.25356. PMID 9738002.
11. De Valck D, Heyninck K, Van Criekinge W, Vandenabeele P, Fiers W, Beyaert R (Sep 1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochemical and Biophysical Research Communications 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. PMID 9299557.
12. Johnson BA, Stehn JR, Yaffe MB, Blackwell TK (May 2002). "Cytoplasmic localization of tristetraprolin involves 14-3-3-dependent and -independent mechanisms". The Journal of Biological Chemistry 277 (20): 18029–36. doi:10.1074/jbc.M110465200. PMID 11886850.

Further reading

• Kino T, Pavlakis GN (Apr 2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
• Kino T, Chrousos GP (Jun 2004). "Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome?". Annals of the New York Academy of Sciences 1024: 153–67. doi:10.1196/annals.1321.013. PMID 15265780.
• Ichimura-Ohshima Y, Morii K, Ichimura T, Araki K, Takahashi Y, Isobe T, Minoshima S, Fukuyama R, Shimizu N, Kuwano R (Apr 1992). "cDNA cloning and chromosome assignment of the gene for human brain 14-3-3 protein eta chain". Journal of Neuroscience Research 31 (4): 600–5. doi:10.1002/jnr.490310403. PMID 1578511.
• Ichimura T, Isobe T, Okuyama T, Takahashi N, Araki K, Kuwano R, Takahashi Y (Oct 1988). "Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases". Proceedings of the National Academy of Sciences of the United States of America 85 (19): 7084–8. doi:10.1073/pnas.85.19.7084. PMC 282128. PMID 2902623.
• Ichimura T, Uchiyama J, Kunihiro O, Ito M, Horigome T, Omata S, Shinkai F, Kaji H, Isobe T (Dec 1995). "Identification of the site of interaction of the 14-3-3 protein with phosphorylated tryptophan hydroxylase". The Journal of Biological Chemistry 270 (48): 28515–8. doi:10.1074/jbc.270.48.28515. PMID 7499362.
• Jones DH, Ley S, Aitken A (Jul 1995). "Isoforms of 14-3-3 protein can form homo- and heterodimers in vivo and in vitro: implications for function as adapter proteins". FEBS Letters 368 (1): 55–8. doi:10.1016/0014-5793(95)00598-4. PMID 7615088.
• Wu C, Friedlander P, Lamoureux C, Zannis-Hadjopoulos M, Price GB (Sep 1993). "cDNA clones contain autonomous replication activity". Biochimica et Biophysica Acta 1174 (3): 241–57. doi:10.1016/0167-4781(93)90193-h. PMID 7690594.
• Swanson KD, Dhar MS, Joshi JG (Oct 1993). "The human and bovine 14-3-3 eta protein mRNAs are highly conserved in both their translated and untranslated regions". Biochimica et Biophysica Acta 1216 (1): 145–8. doi:10.1016/0167-4781(93)90053-G. PMID 8218406.
• Leffers H, Madsen P, Rasmussen HH, Honoré B, Andersen AH, Walbum E, Vandekerckhove J, Celis JE (Jun 1993). "Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway". Journal of Molecular Biology 231 (4): 982–98. doi:10.1006/jmbi.1993.1346. PMID 8515476.
• Muratake T, Hayashi S, Ichimura Y, Morii K, Kuwano R, Ichikawa T, Kumanishi T, Isobe T, Watanabe M, Kondo H (1996). "The effect on methamphetamine on the mRNA level for 14.3.3 eta chain in the human cultured cells". Molecular Neurobiology 11 (1-3): 223–30. doi:10.1007/BF02740697. PMID 8561965.
• Tommerup N, Leffers H (Apr 1996). "Assignment of the human genes encoding 14,3-3 Eta (YWHAH) to 22q12, 14-3-3 zeta (YWHAZ) to 2p25.1-p25.2, and 14-3-3 beta (YWHAB) to 20q13.1 by in situ hybridization". Genomics 33 (1): 149–50. doi:10.1006/geno.1996.0176. PMID 8617504.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Papin C, Denouel A, Calothy G, Eychène A (May 1996). "Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system". Oncogene 12 (10): 2213–21. PMID 8668348.
• Vincenz C, Dixit VM (Aug 1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". The Journal of Biological Chemistry 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. PMID 8702721.
• Muratake T, Hayashi S, Ichikawa T, Kumanishi T, Ichimura Y, Kuwano R, Isobe T, Wang Y, Minoshima S, Shimizu N, Takahashi Y (Aug 1996). "Structural organization and chromosomal assignment of the human 14-3-3 eta chain gene (YWHAH)". Genomics 36 (1): 63–9. doi:10.1006/geno.1996.0426. PMID 8812417.
• Wakui H, Wright AP, Gustafsson J, Zilliacus J (Mar 1997). "Interaction of the ligand-activated glucocorticoid receptor with the 14-3-3 eta protein". The Journal of Biological Chemistry 272 (13): 8153–6. doi:10.1074/jbc.272.13.8153. PMID 9079630.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS, Piwnica-Worms H (Sep 1997). "Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216". Science 277 (5331): 1501–5. doi:10.1126/science.277.5331.1501. PMID 9278512.
• De Valck D, Heyninck K, Van Criekinge W, Vandenabeele P, Fiers W, Beyaert R (Sep 1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochemical and Biophysical Research Communications 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. PMID 9299557.
• Hsu SY, Kaipia A, Zhu L, Hsueh AJ (Nov 1997). "Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11". Molecular Endocrinology 11 (12): 1858–67. doi:10.1210/me.11.12.1858. PMID 9369453.