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Identification
HMDB Protein ID HMDBP02552
Secondary Accession Numbers
  • 8051
Name 14-3-3 protein zeta/delta
Synonyms
  1. KCIP-1
  2. Protein kinase C inhibitor protein 1
Gene Name YWHAZ
Protein Type Enzyme
Biological Properties
General Function Involved in protein domain specific binding
Specific Function Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathway. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
protein binding
protein domain specific binding
Cellular Location
  1. Cytoplasm
  2. Melanosome
Gene Properties
Chromosome Location Chromosome:8
Locus 8q23.1
SNPs YWHAZ
Gene Sequence
>738 bp
ATGGATAAAAATGAGCTGGTTCAGAAGGCCAAACTGGCCGAGCAGGCTGAGCGATATGAT
GACATGGCAGCCTGCATGAAGTCTGTAACTGAGCAAGGAGCTGAATTATCCAATGAGGAG
AGGAATCTTCTCTCAGTTGCTTATAAAAATGTTGTAGGAGCCCGTAGGTCATCTTGGAGG
GTCGTCTCAAGTATTGAACAAAAGACGGAAGGTGCTGAGAAAAAACAGCAGATGGCTCGA
GAATACAGAGAGAAAATTGAGACGGAGCTAAGAGATATCTGCAATGATGTACTGTCTCTT
TTGGAAAAGTTCTTGATCCCCAATGCTTCACAAGCAGAGAGCAAAGTCTTCTATTTGAAA
ATGAAAGGAGATTACTACCGTTACTTGGCTGAGGTTGCCGCTGGTGATGACAAGAAAGGG
ATTGTCGATCAGTCACAACAAGCATACCAAGAAGCTTTTGAAATCAGCAAAAAGGAAATG
CAACCAACACATCCTATCAGACTGGGTCTGGCCCTTAACTTCTCTGTGTTCTATTATGAG
ATTCTGAACTCCCCAGAGAAAGCCTGCTCTCTTGCAAAGACAGCTTTTGATGAAGCCATT
GCTGAACTTGATACATTAAGTGAAGAGTCATACAAAGACAGCACGCTAATAATGCAATTA
CTGAGAGACAACTTGACATTGTGGACATCGGATACCCAAGGAGACGAAGCTGAAGCAGGA
GAAGGAGGGGAAAATTAA
Protein Properties
Number of Residues 245
Molecular Weight 27744.8
Theoretical pI 4.43
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>14-3-3 protein zeta/delta
MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWR
VVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLK
MKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYE
ILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAG
EGGEN
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P63104
UniProtKB/Swiss-Prot Entry Name 1433Z_HUMAN
PDB IDs
GenBank Gene ID M86400
GeneCard ID YWHAZ
GenAtlas ID YWHAZ
HGNC ID HGNC:12855
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  5. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  7. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  8. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed:17081065 ]
  9. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801 ]
  10. Dubois T, Rommel C, Howell S, Steinhussen U, Soneji Y, Morrice N, Moelling K, Aitken A: 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8. [PubMed:9360956 ]
  11. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O: Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. Epub 2005 Jan 20. [PubMed:15660133 ]
  12. Yoshida K, Yamaguchi T, Natsume T, Kufe D, Miki Y: JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage. Nat Cell Biol. 2005 Mar;7(3):278-85. [PubMed:15696159 ]
  13. Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, Lehrbach GM, Schramek D, Guilhaus M, James DE, Daly RJ: Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J. 2008 Sep 3;27(17):2305-16. [PubMed:19172738 ]
  14. Zupan LA, Steffens DL, Berry CA, Landt M, Gross RW: Cloning and expression of a human 14-3-3 protein mediating phospholipolysis. Identification of an arachidonoyl-enzyme intermediate during catalysis. J Biol Chem. 1992 May 5;267(13):8707-10. [PubMed:1577711 ]
  15. Seluja GA, Elias L, Pietromonaco SF: Two unique 5' untranslated regions in mRNAs encoding human 14-3-3 zeta: differential expression in hemopoietic cells. Biochim Biophys Acta. 1998 Feb 11;1395(3):281-7. [PubMed:9512661 ]
  16. Powell DW, Rane MJ, Chen Q, Singh S, McLeish KR: Identification of 14-3-3zeta as a protein kinase B/Akt substrate. J Biol Chem. 2002 Jun 14;277(24):21639-42. Epub 2002 Apr 15. [PubMed:11956222 ]
  17. Woodcock JM, Murphy J, Stomski FC, Berndt MC, Lopez AF: The dimeric versus monomeric status of 14-3-3zeta is controlled by phosphorylation of Ser58 at the dimer interface. J Biol Chem. 2003 Sep 19;278(38):36323-7. Epub 2003 Jul 15. [PubMed:12865427 ]
  18. Zheng W, Zhang Z, Ganguly S, Weller JL, Klein DC, Cole PA: Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nat Struct Biol. 2003 Dec;10(12):1054-7. Epub 2003 Oct 26. [PubMed:14578935 ]
  19. Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsujimoto Y, Yoshioka K, Masuyama N, Gotoh Y: JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004 Apr 21;23(8):1889-99. Epub 2004 Apr 8. [PubMed:15071501 ]
  20. Nagata-Ohashi K, Ohta Y, Goto K, Chiba S, Mori R, Nishita M, Ohashi K, Kousaka K, Iwamatsu A, Niwa R, Uemura T, Mizuno K: A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia. J Cell Biol. 2004 May 24;165(4):465-71. [PubMed:15159416 ]
  21. Obsilova V, Vecer J, Herman P, Pabianova A, Sulc M, Teisinger J, Boura E, Obsil T: 14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4. Biochemistry. 2005 Aug 30;44(34):11608-17. [PubMed:16114898 ]
  22. Ma Y, Pitson S, Hercus T, Murphy J, Lopez A, Woodcock J: Sphingosine activates protein kinase A type II by a novel cAMP-independent mechanism. J Biol Chem. 2005 Jul 15;280(28):26011-7. Epub 2005 May 9. [PubMed:15883165 ]
  23. Ganguly S, Weller JL, Ho A, Chemineau P, Malpaux B, Klein DC: Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1222-7. Epub 2005 Jan 11. [PubMed:15644438 ]
  24. Gu YM, Jin YH, Choi JK, Baek KH, Yeo CY, Lee KY: Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006 Jan 9;580(1):305-10. Epub 2005 Dec 19. [PubMed:16376338 ]
  25. Kim JS, Diebold BA, Babior BM, Knaus UG, Bokoch GM: Regulation of Nox1 activity via protein kinase A-mediated phosphorylation of NoxA1 and 14-3-3 binding. J Biol Chem. 2007 Nov 30;282(48):34787-800. Epub 2007 Oct 3. [PubMed:17913709 ]
  26. Zenke FT, Krendel M, DerMardirossian C, King CC, Bohl BP, Bokoch GM: p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor. J Biol Chem. 2004 Apr 30;279(18):18392-400. Epub 2004 Feb 17. [PubMed:14970201 ]
  27. Rittinger K, Budman J, Xu J, Volinia S, Cantley LC, Smerdon SJ, Gamblin SJ, Yaffe MB: Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol Cell. 1999 Aug;4(2):153-66. [PubMed:10488331 ]
  28. Obsil T, Ghirlando R, Klein DC, Ganguly S, Dyda F: Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation. Cell. 2001 Apr 20;105(2):257-67. [PubMed:11336675 ]
  29. Macdonald N, Welburn JP, Noble ME, Nguyen A, Yaffe MB, Clynes D, Moggs JG, Orphanides G, Thomson S, Edmunds JW, Clayton AL, Endicott JA, Mahadevan LC: Molecular basis for the recognition of phosphorylated and phosphoacetylated histone h3 by 14-3-3. Mol Cell. 2005 Oct 28;20(2):199-211. [PubMed:16246723 ]
  30. Ottmann C, Yasmin L, Weyand M, Veesenmeyer JL, Diaz MH, Palmer RH, Francis MS, Hauser AR, Wittinghofer A, Hallberg B: Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis. EMBO J. 2007 Feb 7;26(3):902-13. Epub 2007 Jan 18. [PubMed:17235285 ]