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Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
Protein YWHAZ PDB 1a37.png
PDB rendering based on 1a37.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols YWHAZ ; 14-3-3-zeta; HEL-S-3; HEL4; KCIP-1; YWHAD
External IDs OMIM601288 MGI109484 HomoloGene56528 GeneCards: YWHAZ Gene
RNA expression pattern
PBB GE YWHAZ 200640 at tn.png
PBB GE YWHAZ 200638 s at tn.png
PBB GE YWHAZ 200639 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7534 22631
Ensembl ENSG00000164924 ENSMUSG00000022285
UniProt P63104 P63101
RefSeq (mRNA) NM_001135699 NM_001253805
RefSeq (protein) NP_001129171 NP_001240734
Location (UCSC) Chr 8:
101.93 – 101.97 Mb
Chr 15:
36.77 – 36.79 Mb
PubMed search [1] [2]

14-3-3 protein zeta/delta is a protein that in humans is encoded by the YWHAZ gene.[1]


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 sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Two transcript variants differing in the 5' UTR, but encoding the same protein, have been identified for this gene.[2]


YWHAZ has been shown to interact with:

See also[edit]


  1. ^ Tommerup N, Leffers H (June 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. 
  2. ^ "Entrez Gene: YWHAZ tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide". 
  3. ^ Powell DW, Rane MJ, Chen Q, Singh S, McLeish KR (June 2002). "Identification of 14-3-3zeta as a protein kinase B/Akt substrate". J. Biol. Chem. 277 (24): 21639–42. doi:10.1074/jbc.M203167200. PMID 11956222. 
  4. ^ Garcia-Guzman M, Dolfi F, Russello M, Vuori K (February 1999). "Cell adhesion regulates the interaction between the docking protein p130(Cas) and the 14-3-3 proteins". J. Biol. Chem. 274 (9): 5762–8. doi:10.1074/jbc.274.9.5762. PMID 10026197. 
  5. ^ Yang H, Masters SC, Wang H, Fu H (June 2001). "The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta". Biochim. Biophys. Acta 1547 (2): 313–9. doi:10.1016/s0167-4838(01)00202-3. PMID 11410287. 
  6. ^ Clark GJ, Drugan JK, Rossman KL, Carpenter JW, Rogers-Graham K, Fu H, Der CJ, Campbell SL (August 1997). "14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1 cysteine-rich domain". J. Biol. Chem. 272 (34): 20990–3. doi:10.1074/jbc.272.34.20990. PMID 9261098. 
  7. ^ a b Tzivion G, Luo ZJ, Avruch J (September 2000). "Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo". J. Biol. Chem. 275 (38): 29772–8. doi:10.1074/jbc.M001207200. PMID 10887173. 
  8. ^ Koyama S, Williams LT, Kikuchi A (July 1995). "Characterization of the interaction of Raf-1 with ras p21 or 14-3-3 protein in intact cells". FEBS Lett. 368 (2): 321–5. doi:10.1016/0014-5793(95)00686-4. PMID 7628630. 
  9. ^ a b Van Der Hoeven PC, Van Der Wal JC, Ruurs P, Van Dijk MC, Van Blitterswijk J (January 2000). "14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation". Biochem. J. 345 (2): 297–306. doi:10.1042/0264-6021:3450297. PMC 1220759. PMID 10620507. 
  10. ^ Chow CW, Davis RJ (January 2000). "Integration of calcium and cyclic AMP signaling pathways by 14-3-3". Mol. Cell. Biol. 20 (2): 702–12. doi:10.1128/MCB.20.2.702-712.2000. PMC 85175. PMID 10611249. 
  11. ^ Mils V, Baldin V, Goubin F, Pinta I, Papin C, Waye M, Eychene A, Ducommun B (March 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. 
  12. ^ a b Calverley DC, Kavanagh TJ, Roth GJ (February 1998). "Human signaling protein 14-3-3zeta interacts with platelet glycoprotein Ib subunits Ibalpha and Ibbeta". Blood 91 (4): 1295–303. PMID 9454760. 
  13. ^ a b Feng S, Christodoulides N, Reséndiz JC, Berndt MC, Kroll MH (January 2000). "Cytoplasmic domains of GpIbalpha and GpIbbeta regulate 14-3-3zeta binding to GpIb/IX/V". Blood 95 (2): 551–7. PMID 10627461. 
  14. ^ Du X, Fox JE, Pei S (March 1996). "Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha". J. Biol. Chem. 271 (13): 7362–7. doi:10.1074/jbc.271.13.7362. PMID 8631758. 
  15. ^ Du X, Harris SJ, Tetaz TJ, Ginsberg MH, Berndt MC (July 1994). "Association of a phospholipase A2 (14-3-3 protein) with the platelet glycoprotein Ib-IX complex". J. Biol. Chem. 269 (28): 18287–90. PMID 8034572. 
  16. ^ Prymakowska-Bosak M, Hock R, Catez F, Lim JH, Birger Y, Shirakawa H, Lee K, Bustin M (October 2002). "Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and promotes interaction with 14.3.3 proteins". Mol. Cell. Biol. 22 (19): 6809–19. doi:10.1128/mcb.22.19.6809-6819.2002. PMC 134047. PMID 12215538. 
  17. ^ Sliva D, Gu M, Zhu YX, Chen J, Tsai S, Du X, Yang YC (February 2000). "14-3-3zeta interacts with the alpha-chain of human interleukin 9 receptor". Biochem. J. 345 (3): 741–7. doi:10.1042/0264-6021:3450741. PMC 1220812. PMID 10642536. 
  18. ^ Birkenfeld J, Betz H, Roth D (January 2003). "Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta". Biochem. J. 369 (Pt 1): 45–54. doi:10.1042/BJ20021152. PMC 1223062. PMID 12323073. 
  19. ^ Waterman MJ, Stavridi ES, Waterman JL, Halazonetis TD (June 1998). "ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins". Nat. Genet. 19 (2): 175–8. doi:10.1038/542. PMID 9620776. 
  20. ^ Gannon-Murakami L, Murakami K (June 2002). "Selective association of protein kinase C with 14-3-3 zeta in neuronally differentiated PC12 Cells. Stimulatory and inhibitory effect of 14-3-3 zeta in vivo". J. Biol. Chem. 277 (26): 23116–22. doi:10.1074/jbc.M201478200. PMID 11950841. 
  21. ^ Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (August 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochem. Biophys. Res. Commun. 307 (3): 459–65. doi:10.1016/S0006-291X(03)01187-2. PMID 12893243. 
  22. ^ De Valck D, Heyninck K, Van Criekinge W, Vandenabeele P, Fiers W, Beyaert R (September 1997). "A20 inhibits NF-kappaB activation independently of binding to 14-3-3 proteins". Biochem. Biophys. Res. Commun. 238 (2): 590–4. doi:10.1006/bbrc.1997.7343. PMID 9299557. 
  23. ^ Vincenz C, Dixit VM (August 1996). "14-3-3 proteins associate with A20 in an isoform-specific manner and function both as chaperone and adapter molecules". J. Biol. Chem. 271 (33): 20029–34. doi:10.1074/jbc.271.33.20029. PMID 8702721. 
  24. ^ Nellist M, Goedbloed MA, de Winter C, Verhaaf B, Jankie A, Reuser AJ, van den Ouweland AM, van der Sluijs P, Halley DJ (October 2002). "Identification and characterization of the interaction between tuberin and 14-3-3zeta". J. Biol. Chem. 277 (42): 39417–24. doi:10.1074/jbc.M204802200. PMID 12176984. 
  25. ^ Hashiguchi M, Sobue K, Paudel HK (August 2000). "14-3-3zeta is an effector of tau protein phosphorylation". J. Biol. Chem. 275 (33): 25247–54. doi:10.1074/jbc.M003738200. PMID 10840038. 

Further reading[edit]

  • Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377. 
  • Kino T, Chrousos GP (2004). "Human immunodeficiency virus type-1 accessory protein Vpr: a causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome?". Ann. N. Y. Acad. Sci. 1024: 153–67. doi:10.1196/annals.1321.013. PMID 15265780. 
  • Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P (2006). "New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium". Front. Biosci. 11: 1646–66. doi:10.2741/1911. PMID 16368544.