Full text data of YWHAZ
YWHAZ
[Confidence: high (present in two of the MS resources)]
14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1; KCIP-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1; KCIP-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00021263
IPI00021263 14-3-3 protein zeta/delta ( Protein kinase C inhibitor protein-1, KCIP-1) 14-3-3 protein zeta/delta ( Protein kinase C inhibitor protein-1, KCIP-1) membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band ~ 14 kDa
IPI00021263 14-3-3 protein zeta/delta ( Protein kinase C inhibitor protein-1, KCIP-1) 14-3-3 protein zeta/delta ( Protein kinase C inhibitor protein-1, KCIP-1) membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band ~ 14 kDa
UniProt
P63104
ID 1433Z_HUMAN Reviewed; 245 AA.
AC P63104; A8K1N0; B7Z465; P29213; P29312; Q32P43; Q5XJ08; Q6GPI2;
read moreAC Q6IN74; Q6NUR9; Q6P3U9; Q86V33;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=14-3-3 protein zeta/delta;
DE AltName: Full=Protein kinase C inhibitor protein 1;
DE Short=KCIP-1;
GN Name=YWHAZ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=1577711;
RA Zupan L.A., Steffens D.L., Berry C.A., Landt M.L., Gross R.W.;
RT "Cloning and expression of a human 14-3-3 protein mediating
RT phospholipolysis. Identification of an arachidonoyl-enzyme
RT intermediate during catalysis.";
RL J. Biol. Chem. 267:8707-8710(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9512661; DOI=10.1016/S0167-4781(97)00171-1;
RA Seluja G.A., Pietromonaco S.F., Elias L.;
RT "Two unique 5' untranslated regions in mRNAs encoding human 14-3-3
RT zeta: differential expression in hemopoietic cells.";
RL Biochim. Biophys. Acta 1395:281-287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Colon, Eye, Melanoma, PNS, Skin, Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-18.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 1-9; 12-18; 28-49; 61-68; 86-91; 128-158 AND
RP 213-222, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Platelet;
RA Bienvenut W.V., Potts A., Barblan J., Claeys D., Quadroni M.;
RL Submitted (NOV-2005) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 92-103; 140-157; 194-212 AND 223-245, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP PHOSPHORYLATION AT THR-232, INTERACTION WITH RAF1, AND FUNCTION.
RX PubMed=9360956; DOI=10.1074/jbc.272.46.28882;
RA Dubois T., Rommel C., Howell S., Steinhussen U., Soneji Y.,
RA Morrice N., Moelling K., Aitken A.;
RT "14-3-3 is phosphorylated by casein kinase I on residue 233.
RT Phosphorylation at this site in vivo regulates Raf/14-3-3
RT interaction.";
RL J. Biol. Chem. 272:28882-28888(1997).
RN [10]
RP INTERACTION WITH TLK2.
RX PubMed=10455159; DOI=10.1074/jbc.274.35.24865;
RA Zhang S., Xing H., Muslin A.J.;
RT "Nuclear localization of protein kinase U-alpha is regulated by 14-3-
RT 3.";
RL J. Biol. Chem. 274:24865-24872(1999).
RN [11]
RP INTERACTION WITH AANAT.
RX PubMed=11427721; DOI=10.1073/pnas.141118798;
RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H.,
RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T.,
RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.;
RT "Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-
RT 3-3-binding switch in melatonin synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001).
RN [12]
RP PHOSPHORYLATION AT SER-58, AND INTERACTION WITH AKT1.
RX PubMed=11956222; DOI=10.1074/jbc.M203167200;
RA Powell D.W., Rane M.J., Chen Q., Singh S., McLeish K.R.;
RT "Identification of 14-3-3zeta as a protein kinase B/Akt substrate.";
RL J. Biol. Chem. 277:21639-21642(2002).
RN [13]
RP PHOSPHORYLATION AT SER-58, AND DIMERIZATION.
RX PubMed=12865427; DOI=10.1074/jbc.M304689200;
RA Woodcock J.M., Murphy J., Stomski F.C., Berndt M.C., Lopez A.F.;
RT "The dimeric versus monomeric status of 14-3-3zeta is controlled by
RT phosphorylation of Ser58 at the dimer interface.";
RL J. Biol. Chem. 278:36323-36327(2003).
RN [14]
RP INTERACTION WITH AANAT, AND FUNCTION.
RX PubMed=14578935; DOI=10.1038/nsb1005;
RA Zheng W., Zhang Z., Ganguly S., Weller J.L., Klein D.C., Cole P.A.;
RT "Cellular stabilization of the melatonin rhythm enzyme induced by
RT nonhydrolyzable phosphonate incorporation.";
RL Nat. Struct. Biol. 10:1054-1057(2003).
RN [15]
RP PHOSPHORYLATION AT SER-184, INTERACTION WITH BAX, FUNCTION, AND
RP MUTAGENESIS OF SER-184.
RX PubMed=15071501; DOI=10.1038/sj.emboj.7600194;
RA Tsuruta F., Sunayama J., Mori Y., Hattori S., Shimizu S.,
RA Tsujimoto Y., Yoshioka K., Masuyama N., Gotoh Y.;
RT "JNK promotes Bax translocation to mitochondria through
RT phosphorylation of 14-3-3 proteins.";
RL EMBO J. 23:1889-1899(2004).
RN [16]
RP INTERACTION WITH SSH1.
RX PubMed=15159416; DOI=10.1083/jcb.200401136;
RA Nagata-Ohashi K., Ohta Y., Goto K., Chiba S., Mori R., Nishita M.,
RA Ohashi K., Kousaka K., Iwamatsu A., Niwa R., Uemura T., Mizuno K.;
RT "A pathway of neuregulin-induced activation of cofilin-phosphatase
RT Slingshot and cofilin in lamellipodia.";
RL J. Cell Biol. 165:465-471(2004).
RN [17]
RP INTERACTION WITH MLLT7.
RX PubMed=16114898; DOI=10.1021/bi050618r;
RA Obsilova V., Vecer J., Herman P., Pabianova A., Sulc M., Teisinger J.,
RA Boura E., Obsil T.;
RT "14-3-3 protein interacts with nuclear localization sequence of
RT forkhead transcription factor FoxO4.";
RL Biochemistry 44:11608-11617(2005).
RN [18]
RP INTERACTION WITH SSH1.
RX PubMed=15660133; DOI=10.1038/sj.emboj.7600543;
RA Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N.,
RA Sarcevic B., Sampath R., Bamburg J.R., Bernard O.;
RT "Interplay between components of a novel LIM kinase-slingshot
RT phosphatase complex regulates cofilin.";
RL EMBO J. 24:473-486(2005).
RN [19]
RP PHOSPHORYLATION AT SER-58, AND MUTAGENESIS OF SER-58.
RX PubMed=15883165; DOI=10.1074/jbc.M409081200;
RA Ma Y., Pitson S., Hercus T., Murphy J., Lopez A., Woodcock J.;
RT "Sphingosine activates protein kinase A type II by a novel cAMP-
RT independent mechanism.";
RL J. Biol. Chem. 280:26011-26017(2005).
RN [20]
RP INTERACTION WITH ABL1, MASS SPECTROMETRY, PHOSPHORYLATION AT SER-184,
RP AND MUTAGENESIS OF SER-184.
RX PubMed=15696159; DOI=10.1038/ncb1228;
RA Yoshida K., Yamaguchi T., Natsume T., Kufe D., Miki Y.;
RT "JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of
RT c-Abl in the apoptotic response to DNA damage.";
RL Nat. Cell Biol. 7:278-285(2005).
RN [21]
RP INTERACTION WITH AANAT, AND FUNCTION.
RX PubMed=15644438; DOI=10.1073/pnas.0406871102;
RA Ganguly S., Weller J.L., Ho A., Chemineau P., Malpaux B., Klein D.C.;
RT "Melatonin synthesis: 14-3-3-dependent activation and inhibition of
RT arylalkylamine N-acetyltransferase mediated by phosphoserine-205.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1222-1227(2005).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [23]
RP PHOSPHORYLATION AT SER-58, DIMERIZATION, INTERACTION WITH TP53 AND
RP YWHAE, FUNCTION, AND MUTAGENESIS OF SER-58.
RX PubMed=16376338; DOI=10.1016/j.febslet.2005.12.024;
RA Gu Y.-M., Jin Y.-H., Choi J.-K., Baek K.-H., Yeo C.-Y., Lee K.-Y.;
RT "Protein kinase A phosphorylates and regulates dimerization of 14-3-3
RT epsilon.";
RL FEBS Lett. 580:305-310(2006).
RN [24]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [25]
RP INTERACTION WITH NOXA1, AND MUTAGENESIS OF LYS-49.
RX PubMed=17913709; DOI=10.1074/jbc.M704754200;
RA Kim J.-S., Diebold B.A., Babior B.M., Knaus U.G., Bokoch G.M.;
RT "Regulation of Nox1 activity via PKA-mediated phosphorylation of NoxA1
RT and 14-3-3 binding.";
RL J. Biol. Chem. 282:34787-34800(2007).
RN [26]
RP INTERACTION WITH ARHGEF2.
RX PubMed=14970201; DOI=10.1074/jbc.M400084200;
RA Zenke F.T., Krendel M., DerMardirossian C., King C.C., Bohl B.P.,
RA Bokoch G.M.;
RT "p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to
RT GEF-H1, a microtubule-localized Rho exchange factor.";
RL J. Biol. Chem. 279:18392-18400(2004).
RN [27]
RP INTERACTION WITH GAB2.
RX PubMed=19172738; DOI=10.1038/emboj.2008.159;
RA Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P.,
RA Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D.,
RA Guilhaus M., James D.E., Daly R.J.;
RT "Phosphorylation-dependent binding of 14-3-3 terminates signalling by
RT the Gab2 docking protein.";
RL EMBO J. 27:2305-2316(2008).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-3 AND LYS-68, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207 AND THR-232, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=10488331; DOI=10.1016/S1097-2765(00)80363-9;
RA Rittinger K., Budman J., Xu J., Volinia S., Cantley L.C.,
RA Smerdon S.J., Gamblin S.J., Yaffe M.B.;
RT "Structural analysis of 14-3-3 phosphopeptide complexes identifies a
RT dual role for the nuclear export signal of 14-3-3 in ligand binding.";
RL Mol. Cell 4:153-166(1999).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH AANAT.
RX PubMed=11336675; DOI=10.1016/S0092-8674(01)00316-6;
RA Obsil T., Ghirlando R., Klein D.C., Ganguly S., Dyda F.;
RT "Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase
RT complex. a role for scaffolding in enzyme regulation.";
RL Cell 105:257-267(2001).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH HISTONE H3
RP PHOSPHOPEPTIDE.
RX PubMed=16246723; DOI=10.1016/j.molcel.2005.08.032;
RA Macdonald N., Welburn J.P.I., Noble M.E.M., Nguyen A., Yaffe M.B.,
RA Clynes D., Moggs J.G., Orphanides G., Thomson S., Edmunds J.W.,
RA Clayton A.L., Endicott J.A., Mahadevan L.C.;
RT "Molecular basis for the recognition of phosphorylated and
RT phosphoacetylated histone h3 by 14-3-3.";
RL Mol. Cell 20:199-211(2005).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-230 IN COMPLEX WITH
RP PSEUDOMONAS AERUGINOSA EXOS.
RX PubMed=17235285; DOI=10.1038/sj.emboj.7601530;
RA Ottmann C., Yasmin L., Weyand M., Veesenmeyer J.L., Diaz M.H.,
RA Palmer R.H., Francis M.S., Hauser A.R., Wittinghofer A., Hallberg B.;
RT "Phosphorylation-independent interaction between 14-3-3 and exoenzyme
RT S: from structure to pathogenesis.";
RL EMBO J. 26:902-913(2007).
CC -!- FUNCTION: Adapter protein implicated in the regulation of a large
CC spectrum of both general and specialized signaling pathways. Binds
CC to a large number of partners, usually by recognition of a
CC phosphoserine or phosphothreonine motif. Binding generally results
CC in the modulation of the activity of the binding partner.
CC -!- SUBUNIT: Interacts with CDK16 and BSPRY (By similarity). Interacts
CC with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity).
CC Interacts with MLF1 (phosphorylated form); the interaction retains
CC it in the cytoplasm (By similarity). Interacts with Thr-
CC phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By
CC similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and
CC hetero-dimerization is inhibited by phosphorylation on Ser-58.
CC Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with
CC Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts
CC with BAX; the interaction occurs in the cytoplasm. Under stress
CC conditions, MAPK8-mediated phosphorylation releases BAX to
CC mitochondria. Interacts with phosphorylated RAF1; the interaction
CC is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts
CC with TP53; the interaction enhances p53 transcriptional activity.
CC The Ser-58 phosphorylated form inhibits this interaction and p53
CC transcriptional activity. Interacts with ABL1 (phosphorylated
CC form); the interaction retains ABL1 in the cytoplasm. Interacts
CC with PKA-phosphorylated AANAT; the interaction modulates AANAT
CC enzymatic activity by increasing affinity for arylalkylamines and
CC acetyl-CoA and protecting the enzyme from dephosphorylation and
CC proteasomal degradation. It may also prevent thiol-dependent
CC inactivation. Interacts with AKT1; the interaction phosphorylates
CC YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-347088, EBI-347088;
CC Q29495:AANAT (xeno); NbExp=3; IntAct=EBI-347088, EBI-446413;
CC P00519:ABL1; NbExp=2; IntAct=EBI-347088, EBI-375543;
CC P60709:ACTB; NbExp=3; IntAct=EBI-347088, EBI-353944;
CC Q9P0K1:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567236;
CC Q9P0K1-3:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567267;
CC P10398:ARAF; NbExp=3; IntAct=EBI-347088, EBI-365961;
CC Q92974:ARHGEF2; NbExp=2; IntAct=EBI-347088, EBI-302405;
CC P25705:ATP5A1; NbExp=3; IntAct=EBI-347088, EBI-351437;
CC P06576:ATP5B; NbExp=2; IntAct=EBI-347088, EBI-356231;
CC Q92934:BAD; NbExp=5; IntAct=EBI-347088, EBI-700771;
CC Q61337:Bad (xeno); NbExp=3; IntAct=EBI-347088, EBI-400328;
CC P15056:BRAF; NbExp=3; IntAct=EBI-347088, EBI-365980;
CC P62158:CALM3; NbExp=2; IntAct=EBI-347088, EBI-397435;
CC O00257-3:CBX4; NbExp=2; IntAct=EBI-347088, EBI-4392727;
CC P30304:CDC25A; NbExp=2; IntAct=EBI-347088, EBI-747671;
CC P30305:CDC25B; NbExp=4; IntAct=EBI-347088, EBI-1051746;
CC Q00537:CDK17; NbExp=2; IntAct=EBI-347088, EBI-624648;
CC Q07002:CDK18; NbExp=2; IntAct=EBI-347088, EBI-746238;
CC P23528:CFL1; NbExp=3; IntAct=EBI-347088, EBI-352733;
CC P31327:CPS1; NbExp=2; IntAct=EBI-347088, EBI-536811;
CC P67828:CSNK1A1 (xeno); NbExp=4; IntAct=EBI-347088, EBI-7540603;
CC P68104:EEF1A1; NbExp=2; IntAct=EBI-347088, EBI-352162;
CC P00533:EGFR; NbExp=4; IntAct=EBI-347088, EBI-297353;
CC P06733:ENO1; NbExp=2; IntAct=EBI-347088, EBI-353877;
CC Q16658:FSCN1; NbExp=3; IntAct=EBI-347088, EBI-351076;
CC P30793:GCH1; NbExp=4; IntAct=EBI-347088, EBI-958183;
CC P49841:GSK3B; NbExp=4; IntAct=EBI-347088, EBI-373586;
CC P56524:HDAC4; NbExp=5; IntAct=EBI-347088, EBI-308629;
CC Q9UQL6:HDAC5; NbExp=2; IntAct=EBI-347088, EBI-715576;
CC Q8WUI4:HDAC7; NbExp=3; IntAct=EBI-347088, EBI-1048378;
CC P0C0S8:HIST1H2AM; NbExp=2; IntAct=EBI-347088, EBI-1390628;
CC P68431:HIST1H3D; NbExp=3; IntAct=EBI-347088, EBI-79722;
CC P62805:HIST2H4B; NbExp=3; IntAct=EBI-347088, EBI-302023;
CC P07910:HNRNPC; NbExp=2; IntAct=EBI-347088, EBI-357966;
CC P04792:HSPB1; NbExp=2; IntAct=EBI-347088, EBI-352682;
CC Q02241:KIF23; NbExp=5; IntAct=EBI-347088, EBI-306852;
CC P02545:LMNA; NbExp=2; IntAct=EBI-347088, EBI-351935;
CC Q5S007:LRRK2; NbExp=4; IntAct=EBI-347088, EBI-5323863;
CC Q99683:MAP3K5; NbExp=3; IntAct=EBI-347088, EBI-476263;
CC P10636:MAPT; NbExp=8; IntAct=EBI-347088, EBI-366182;
CC P10636-3:MAPT; NbExp=9; IntAct=EBI-347088, EBI-7145070;
CC P29172:MAPT (xeno); NbExp=2; IntAct=EBI-347088, EBI-7291149;
CC Q7KZI7:MARK2; NbExp=6; IntAct=EBI-347088, EBI-516560;
CC P27448:MARK3; NbExp=9; IntAct=EBI-347088, EBI-707595;
CC Q9NYL2:MLTK; NbExp=4; IntAct=EBI-347088, EBI-602273;
CC P19338:NCL; NbExp=2; IntAct=EBI-347088, EBI-346967;
CC P06748:NPM1; NbExp=2; IntAct=EBI-347088, EBI-78579;
CC Q8TEW0:PARD3; NbExp=4; IntAct=EBI-347088, EBI-81968;
CC Q02156:PRKCE; NbExp=5; IntAct=EBI-347088, EBI-706254;
CC O14744:PRMT5; NbExp=2; IntAct=EBI-347088, EBI-351098;
CC P04049:RAF1; NbExp=13; IntAct=EBI-347088, EBI-365996;
CC Q8NFH8-2:REPS2; NbExp=2; IntAct=EBI-347088, EBI-8029141;
CC P61587:RND3; NbExp=11; IntAct=EBI-347088, EBI-1111534;
CC P61588:Rnd3 (xeno); NbExp=3; IntAct=EBI-347088, EBI-6930266;
CC P23396:RPS3; NbExp=2; IntAct=EBI-347088, EBI-351193;
CC P31947:SFN; NbExp=2; IntAct=EBI-347088, EBI-476295;
CC P57059:SIK1; NbExp=4; IntAct=EBI-347088, EBI-1181640;
CC Q9Y2K2:SIK3; NbExp=5; IntAct=EBI-347088, EBI-1181460;
CC O94875:SORBS2; NbExp=2; IntAct=EBI-347088, EBI-311323;
CC Q15831:STK11; NbExp=6; IntAct=EBI-347088, EBI-306838;
CC O00506:STK25; NbExp=2; IntAct=EBI-347088, EBI-618295;
CC P36897:TGFBR1; NbExp=4; IntAct=EBI-347088, EBI-1027557;
CC P04637:TP53; NbExp=2; IntAct=EBI-347088, EBI-366083;
CC P49815:TSC2; NbExp=8; IntAct=EBI-347088, EBI-396587;
CC P55072:VCP; NbExp=2; IntAct=EBI-347088, EBI-355164;
CC P08670:VIM; NbExp=2; IntAct=EBI-347088, EBI-353844;
CC P30291:WEE1; NbExp=3; IntAct=EBI-347088, EBI-914695;
CC P46937:YAP1; NbExp=3; IntAct=EBI-347088, EBI-1044059;
CC P62258:YWHAE; NbExp=5; IntAct=EBI-347088, EBI-356498;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Located to stage
CC I to stage IV melanosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63104-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P63104-2; Sequence=VSP_047505;
CC Note=No experimental confirmation available;
CC -!- PTM: The delta, brain-specific form differs from the zeta form in
CC being phosphorylated (By similarity). Phosphorylation on Ser-184
CC by MAPK8; promotes dissociation of BAX and translocation of BAX to
CC mitochondria. Phosphorylation on Thr-232; inhibits binding of
CC RAF1. Phosphorylated on Ser-58 by PKA and protein kinase C delta
CC type catalytic subunit in a sphingosine-dependent fashion.
CC Phosphorylation on Ser-58 by PKA; disrupts homodimerization and
CC heterodimerization with YHAE and TP53.
CC -!- SIMILARITY: Belongs to the 14-3-3 family.
CC -!- CAUTION: Was originally (PubMed:1577711) thought to have
CC phospholipase A2 activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51814.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH73141.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M86400; AAA36446.1; -; mRNA.
DR EMBL; U28964; AAC52052.1; -; mRNA.
DR EMBL; AK289945; BAF82634.1; -; mRNA.
DR EMBL; AK296902; BAH12451.1; -; mRNA.
DR EMBL; CH471060; EAW91823.1; -; Genomic_DNA.
DR EMBL; BC003623; AAH03623.3; -; mRNA.
DR EMBL; BC051814; AAH51814.1; ALT_INIT; mRNA.
DR EMBL; BC063824; AAH63824.2; -; mRNA.
DR EMBL; BC068456; AAH68456.2; -; mRNA.
DR EMBL; BC072426; AAH72426.2; -; mRNA.
DR EMBL; BC073141; AAH73141.1; ALT_INIT; mRNA.
DR EMBL; BC083508; AAH83508.2; -; mRNA.
DR EMBL; BC099904; AAH99904.1; -; mRNA.
DR EMBL; BC101483; AAI01484.1; -; mRNA.
DR EMBL; BC108281; AAI08282.1; -; mRNA.
DR EMBL; BC111951; AAI11952.1; -; mRNA.
DR PIR; A38246; PSHUAM.
DR RefSeq; NP_001129171.1; NM_001135699.1.
DR RefSeq; NP_001129172.1; NM_001135700.1.
DR RefSeq; NP_001129173.1; NM_001135701.1.
DR RefSeq; NP_001129174.1; NM_001135702.1.
DR RefSeq; NP_003397.1; NM_003406.3.
DR RefSeq; NP_663723.1; NM_145690.2.
DR RefSeq; XP_005251118.1; XM_005251061.1.
DR RefSeq; XP_005251119.1; XM_005251062.1.
DR RefSeq; XP_005251120.1; XM_005251063.1.
DR RefSeq; XP_005251121.1; XM_005251064.1.
DR UniGene; Hs.492407; -.
DR PDB; 1IB1; X-ray; 2.70 A; A/B/C/D=1-245.
DR PDB; 1QJA; X-ray; 2.00 A; A/B=1-245.
DR PDB; 1QJB; X-ray; 2.00 A; A/B=1-245.
DR PDB; 2C1J; X-ray; 2.60 A; A/B=1-245.
DR PDB; 2C1N; X-ray; 2.00 A; A/B=1-245.
DR PDB; 2O02; X-ray; 1.50 A; A/B=1-230.
DR PDB; 2WH0; X-ray; 2.25 A; A/B/C/D=1-245.
DR PDB; 3CU8; X-ray; 2.40 A; A/B=1-245.
DR PDB; 3NKX; X-ray; 2.40 A; A/B=1-245.
DR PDB; 3RDH; X-ray; 2.39 A; A/B/C/D=1-245.
DR PDB; 4BG6; X-ray; 2.30 A; A/B=1-245.
DR PDB; 4FJ3; X-ray; 1.95 A; A/B=1-230.
DR PDB; 4HKC; X-ray; 2.20 A; A=1-245.
DR PDB; 4IHL; X-ray; 2.20 A; A/B=1-230.
DR PDBsum; 1IB1; -.
DR PDBsum; 1QJA; -.
DR PDBsum; 1QJB; -.
DR PDBsum; 2C1J; -.
DR PDBsum; 2C1N; -.
DR PDBsum; 2O02; -.
DR PDBsum; 2WH0; -.
DR PDBsum; 3CU8; -.
DR PDBsum; 3NKX; -.
DR PDBsum; 3RDH; -.
DR PDBsum; 4BG6; -.
DR PDBsum; 4FJ3; -.
DR PDBsum; 4HKC; -.
DR PDBsum; 4IHL; -.
DR ProteinModelPortal; P63104; -.
DR SMR; P63104; 1-230.
DR DIP; DIP-563N; -.
DR IntAct; P63104; 514.
DR MINT; MINT-89071; -.
DR DrugBank; DB01381; Ginkgo biloba.
DR PhosphoSite; P63104; -.
DR DMDM; 52000887; -.
DR DOSAC-COBS-2DPAGE; P63104; -.
DR OGP; P63104; -.
DR UCD-2DPAGE; P63104; -.
DR PaxDb; P63104; -.
DR PRIDE; P63104; -.
DR DNASU; 7534; -.
DR Ensembl; ENST00000353245; ENSP00000309503; ENSG00000164924.
DR Ensembl; ENST00000395951; ENSP00000379281; ENSG00000164924.
DR Ensembl; ENST00000395953; ENSP00000379283; ENSG00000164924.
DR Ensembl; ENST00000395956; ENSP00000379286; ENSG00000164924.
DR Ensembl; ENST00000395957; ENSP00000379287; ENSG00000164924.
DR Ensembl; ENST00000395958; ENSP00000379288; ENSG00000164924.
DR Ensembl; ENST00000419477; ENSP00000395114; ENSG00000164924.
DR Ensembl; ENST00000457309; ENSP00000398599; ENSG00000164924.
DR Ensembl; ENST00000522542; ENSP00000430072; ENSG00000164924.
DR GeneID; 7534; -.
DR KEGG; hsa:7534; -.
DR UCSC; uc003yjv.2; human.
DR CTD; 7534; -.
DR GeneCards; GC08M101930; -.
DR HGNC; HGNC:12855; YWHAZ.
DR HPA; CAB005065; -.
DR MIM; 601288; gene.
DR neXtProt; NX_P63104; -.
DR PharmGKB; PA37444; -.
DR eggNOG; COG5040; -.
DR HOVERGEN; HBG050423; -.
DR InParanoid; P63104; -.
DR KO; K16197; -.
DR OrthoDB; EOG7HHWT3; -.
DR PhylomeDB; P63104; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; P63104; -.
DR ChiTaRS; YWHAZ; human.
DR EvolutionaryTrace; P63104; -.
DR GeneWiki; YWHAZ; -.
DR GenomeRNAi; 7534; -.
DR NextBio; 29475; -.
DR PRO; PR:P63104; -.
DR ArrayExpress; P63104; -.
DR Bgee; P63104; -.
DR Genevestigator; P63104; -.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl.
DR Gene3D; 1.20.190.20; -; 1.
DR InterPro; IPR000308; 14-3-3.
DR InterPro; IPR023409; 14-3-3_CS.
DR InterPro; IPR023410; 14-3-3_domain.
DR PANTHER; PTHR18860; PTHR18860; 1.
DR Pfam; PF00244; 14-3-3; 1.
DR PIRSF; PIRSF000868; 14-3-3; 1.
DR PRINTS; PR00305; 1433ZETA.
DR SMART; SM00101; 14_3_3; 1.
DR SUPFAM; SSF48445; SSF48445; 1.
DR PROSITE; PS00796; 1433_1; 1.
DR PROSITE; PS00797; 1433_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1 245 14-3-3 protein zeta/delta.
FT /FTId=PRO_0000058627.
FT SITE 56 56 Interaction with phosphoserine on
FT interacting protein (By similarity).
FT SITE 127 127 Interaction with phosphoserine on
FT interacting protein (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 3 3 N6-acetyllysine.
FT MOD_RES 58 58 Phosphoserine; by PKA and PKB/AKT1.
FT MOD_RES 68 68 N6-acetyllysine.
FT MOD_RES 184 184 Phosphoserine; by MAPK8.
FT MOD_RES 207 207 Phosphoserine.
FT MOD_RES 232 232 Phosphothreonine; by CK1.
FT VAR_SEQ 1 98 MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEER
FT NLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREY
FT REKIETELRDICNDVL -> MSQPCRKLWRHNYETSSCIEF
FT LK (in isoform 2).
FT /FTId=VSP_047505.
FT MUTAGEN 49 49 K->E: Loss of interaction with NOXA1.
FT MUTAGEN 58 58 S->A: Loss of sphingosine-activated PKA
FT phosphorylation. Promotes
FT homodimerization and heterodimerization
FT with YWHAE. Enhanced transcriptional
FT activity of P53.
FT MUTAGEN 58 58 S->E: Loss of homodimerization. Reduced
FT dimerization with YWHAE. Significantly
FT reduced interaction with P53. No
FT enhancement of P53 transcriptional
FT activity.
FT MUTAGEN 184 184 S->A: On DNA damage, loss of MAPK8-
FT mediated phosphorylation. Loss of binding
FT ABL1. Attenuates ABL1-mediated apoptosis.
FT No loss of interaction with BAX under
FT stress conditions. Inhibits translocation
FT of BAX to mitochondria.
FT CONFLICT 22 22 M -> V (in Ref. 5; AAH68456).
FT CONFLICT 136 136 D -> G (in Ref. 3; BAH12451).
FT HELIX 3 15
FT HELIX 19 31
FT HELIX 38 67
FT TURN 69 71
FT HELIX 76 103
FT HELIX 105 108
FT HELIX 112 131
FT HELIX 135 159
FT HELIX 165 180
FT HELIX 185 200
FT HELIX 201 205
FT TURN 208 210
FT HELIX 211 228
SQ SEQUENCE 245 AA; 27745 MW; D464DF2286BBFE60 CRC64;
MDKNELVQKA KLAEQAERYD DMAACMKSVT EQGAELSNEE RNLLSVAYKN VVGARRSSWR
VVSSIEQKTE GAEKKQQMAR EYREKIETEL RDICNDVLSL LEKFLIPNAS QAESKVFYLK
MKGDYYRYLA EVAAGDDKKG IVDQSQQAYQ EAFEISKKEM QPTHPIRLGL ALNFSVFYYE
ILNSPEKACS LAKTAFDEAI AELDTLSEES YKDSTLIMQL LRDNLTLWTS DTQGDEAEAG
EGGEN
//
ID 1433Z_HUMAN Reviewed; 245 AA.
AC P63104; A8K1N0; B7Z465; P29213; P29312; Q32P43; Q5XJ08; Q6GPI2;
read moreAC Q6IN74; Q6NUR9; Q6P3U9; Q86V33;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=14-3-3 protein zeta/delta;
DE AltName: Full=Protein kinase C inhibitor protein 1;
DE Short=KCIP-1;
GN Name=YWHAZ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=1577711;
RA Zupan L.A., Steffens D.L., Berry C.A., Landt M.L., Gross R.W.;
RT "Cloning and expression of a human 14-3-3 protein mediating
RT phospholipolysis. Identification of an arachidonoyl-enzyme
RT intermediate during catalysis.";
RL J. Biol. Chem. 267:8707-8710(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9512661; DOI=10.1016/S0167-4781(97)00171-1;
RA Seluja G.A., Pietromonaco S.F., Elias L.;
RT "Two unique 5' untranslated regions in mRNAs encoding human 14-3-3
RT zeta: differential expression in hemopoietic cells.";
RL Biochim. Biophys. Acta 1395:281-287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Colon, Eye, Melanoma, PNS, Skin, Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-18.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 1-9; 12-18; 28-49; 61-68; 86-91; 128-158 AND
RP 213-222, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Platelet;
RA Bienvenut W.V., Potts A., Barblan J., Claeys D., Quadroni M.;
RL Submitted (NOV-2005) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 92-103; 140-157; 194-212 AND 223-245, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP PHOSPHORYLATION AT THR-232, INTERACTION WITH RAF1, AND FUNCTION.
RX PubMed=9360956; DOI=10.1074/jbc.272.46.28882;
RA Dubois T., Rommel C., Howell S., Steinhussen U., Soneji Y.,
RA Morrice N., Moelling K., Aitken A.;
RT "14-3-3 is phosphorylated by casein kinase I on residue 233.
RT Phosphorylation at this site in vivo regulates Raf/14-3-3
RT interaction.";
RL J. Biol. Chem. 272:28882-28888(1997).
RN [10]
RP INTERACTION WITH TLK2.
RX PubMed=10455159; DOI=10.1074/jbc.274.35.24865;
RA Zhang S., Xing H., Muslin A.J.;
RT "Nuclear localization of protein kinase U-alpha is regulated by 14-3-
RT 3.";
RL J. Biol. Chem. 274:24865-24872(1999).
RN [11]
RP INTERACTION WITH AANAT.
RX PubMed=11427721; DOI=10.1073/pnas.141118798;
RA Ganguly S., Gastel J.A., Weller J.L., Schwartz C., Jaffe H.,
RA Namboodiri M.A., Coon S.L., Hickman A.B., Rollag M., Obsil T.,
RA Beauverger P., Ferry G., Boutin J.A., Klein D.C.;
RT "Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-
RT 3-3-binding switch in melatonin synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8083-8088(2001).
RN [12]
RP PHOSPHORYLATION AT SER-58, AND INTERACTION WITH AKT1.
RX PubMed=11956222; DOI=10.1074/jbc.M203167200;
RA Powell D.W., Rane M.J., Chen Q., Singh S., McLeish K.R.;
RT "Identification of 14-3-3zeta as a protein kinase B/Akt substrate.";
RL J. Biol. Chem. 277:21639-21642(2002).
RN [13]
RP PHOSPHORYLATION AT SER-58, AND DIMERIZATION.
RX PubMed=12865427; DOI=10.1074/jbc.M304689200;
RA Woodcock J.M., Murphy J., Stomski F.C., Berndt M.C., Lopez A.F.;
RT "The dimeric versus monomeric status of 14-3-3zeta is controlled by
RT phosphorylation of Ser58 at the dimer interface.";
RL J. Biol. Chem. 278:36323-36327(2003).
RN [14]
RP INTERACTION WITH AANAT, AND FUNCTION.
RX PubMed=14578935; DOI=10.1038/nsb1005;
RA Zheng W., Zhang Z., Ganguly S., Weller J.L., Klein D.C., Cole P.A.;
RT "Cellular stabilization of the melatonin rhythm enzyme induced by
RT nonhydrolyzable phosphonate incorporation.";
RL Nat. Struct. Biol. 10:1054-1057(2003).
RN [15]
RP PHOSPHORYLATION AT SER-184, INTERACTION WITH BAX, FUNCTION, AND
RP MUTAGENESIS OF SER-184.
RX PubMed=15071501; DOI=10.1038/sj.emboj.7600194;
RA Tsuruta F., Sunayama J., Mori Y., Hattori S., Shimizu S.,
RA Tsujimoto Y., Yoshioka K., Masuyama N., Gotoh Y.;
RT "JNK promotes Bax translocation to mitochondria through
RT phosphorylation of 14-3-3 proteins.";
RL EMBO J. 23:1889-1899(2004).
RN [16]
RP INTERACTION WITH SSH1.
RX PubMed=15159416; DOI=10.1083/jcb.200401136;
RA Nagata-Ohashi K., Ohta Y., Goto K., Chiba S., Mori R., Nishita M.,
RA Ohashi K., Kousaka K., Iwamatsu A., Niwa R., Uemura T., Mizuno K.;
RT "A pathway of neuregulin-induced activation of cofilin-phosphatase
RT Slingshot and cofilin in lamellipodia.";
RL J. Cell Biol. 165:465-471(2004).
RN [17]
RP INTERACTION WITH MLLT7.
RX PubMed=16114898; DOI=10.1021/bi050618r;
RA Obsilova V., Vecer J., Herman P., Pabianova A., Sulc M., Teisinger J.,
RA Boura E., Obsil T.;
RT "14-3-3 protein interacts with nuclear localization sequence of
RT forkhead transcription factor FoxO4.";
RL Biochemistry 44:11608-11617(2005).
RN [18]
RP INTERACTION WITH SSH1.
RX PubMed=15660133; DOI=10.1038/sj.emboj.7600543;
RA Soosairajah J., Maiti S., Wiggan O., Sarmiere P., Moussi N.,
RA Sarcevic B., Sampath R., Bamburg J.R., Bernard O.;
RT "Interplay between components of a novel LIM kinase-slingshot
RT phosphatase complex regulates cofilin.";
RL EMBO J. 24:473-486(2005).
RN [19]
RP PHOSPHORYLATION AT SER-58, AND MUTAGENESIS OF SER-58.
RX PubMed=15883165; DOI=10.1074/jbc.M409081200;
RA Ma Y., Pitson S., Hercus T., Murphy J., Lopez A., Woodcock J.;
RT "Sphingosine activates protein kinase A type II by a novel cAMP-
RT independent mechanism.";
RL J. Biol. Chem. 280:26011-26017(2005).
RN [20]
RP INTERACTION WITH ABL1, MASS SPECTROMETRY, PHOSPHORYLATION AT SER-184,
RP AND MUTAGENESIS OF SER-184.
RX PubMed=15696159; DOI=10.1038/ncb1228;
RA Yoshida K., Yamaguchi T., Natsume T., Kufe D., Miki Y.;
RT "JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of
RT c-Abl in the apoptotic response to DNA damage.";
RL Nat. Cell Biol. 7:278-285(2005).
RN [21]
RP INTERACTION WITH AANAT, AND FUNCTION.
RX PubMed=15644438; DOI=10.1073/pnas.0406871102;
RA Ganguly S., Weller J.L., Ho A., Chemineau P., Malpaux B., Klein D.C.;
RT "Melatonin synthesis: 14-3-3-dependent activation and inhibition of
RT arylalkylamine N-acetyltransferase mediated by phosphoserine-205.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1222-1227(2005).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [23]
RP PHOSPHORYLATION AT SER-58, DIMERIZATION, INTERACTION WITH TP53 AND
RP YWHAE, FUNCTION, AND MUTAGENESIS OF SER-58.
RX PubMed=16376338; DOI=10.1016/j.febslet.2005.12.024;
RA Gu Y.-M., Jin Y.-H., Choi J.-K., Baek K.-H., Yeo C.-Y., Lee K.-Y.;
RT "Protein kinase A phosphorylates and regulates dimerization of 14-3-3
RT epsilon.";
RL FEBS Lett. 580:305-310(2006).
RN [24]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [25]
RP INTERACTION WITH NOXA1, AND MUTAGENESIS OF LYS-49.
RX PubMed=17913709; DOI=10.1074/jbc.M704754200;
RA Kim J.-S., Diebold B.A., Babior B.M., Knaus U.G., Bokoch G.M.;
RT "Regulation of Nox1 activity via PKA-mediated phosphorylation of NoxA1
RT and 14-3-3 binding.";
RL J. Biol. Chem. 282:34787-34800(2007).
RN [26]
RP INTERACTION WITH ARHGEF2.
RX PubMed=14970201; DOI=10.1074/jbc.M400084200;
RA Zenke F.T., Krendel M., DerMardirossian C., King C.C., Bohl B.P.,
RA Bokoch G.M.;
RT "p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to
RT GEF-H1, a microtubule-localized Rho exchange factor.";
RL J. Biol. Chem. 279:18392-18400(2004).
RN [27]
RP INTERACTION WITH GAB2.
RX PubMed=19172738; DOI=10.1038/emboj.2008.159;
RA Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P.,
RA Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D.,
RA Guilhaus M., James D.E., Daly R.J.;
RT "Phosphorylation-dependent binding of 14-3-3 terminates signalling by
RT the Gab2 docking protein.";
RL EMBO J. 27:2305-2316(2008).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-3 AND LYS-68, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207 AND THR-232, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [33]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=10488331; DOI=10.1016/S1097-2765(00)80363-9;
RA Rittinger K., Budman J., Xu J., Volinia S., Cantley L.C.,
RA Smerdon S.J., Gamblin S.J., Yaffe M.B.;
RT "Structural analysis of 14-3-3 phosphopeptide complexes identifies a
RT dual role for the nuclear export signal of 14-3-3 in ligand binding.";
RL Mol. Cell 4:153-166(1999).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH AANAT.
RX PubMed=11336675; DOI=10.1016/S0092-8674(01)00316-6;
RA Obsil T., Ghirlando R., Klein D.C., Ganguly S., Dyda F.;
RT "Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase
RT complex. a role for scaffolding in enzyme regulation.";
RL Cell 105:257-267(2001).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH HISTONE H3
RP PHOSPHOPEPTIDE.
RX PubMed=16246723; DOI=10.1016/j.molcel.2005.08.032;
RA Macdonald N., Welburn J.P.I., Noble M.E.M., Nguyen A., Yaffe M.B.,
RA Clynes D., Moggs J.G., Orphanides G., Thomson S., Edmunds J.W.,
RA Clayton A.L., Endicott J.A., Mahadevan L.C.;
RT "Molecular basis for the recognition of phosphorylated and
RT phosphoacetylated histone h3 by 14-3-3.";
RL Mol. Cell 20:199-211(2005).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-230 IN COMPLEX WITH
RP PSEUDOMONAS AERUGINOSA EXOS.
RX PubMed=17235285; DOI=10.1038/sj.emboj.7601530;
RA Ottmann C., Yasmin L., Weyand M., Veesenmeyer J.L., Diaz M.H.,
RA Palmer R.H., Francis M.S., Hauser A.R., Wittinghofer A., Hallberg B.;
RT "Phosphorylation-independent interaction between 14-3-3 and exoenzyme
RT S: from structure to pathogenesis.";
RL EMBO J. 26:902-913(2007).
CC -!- FUNCTION: Adapter protein implicated in the regulation of a large
CC spectrum of both general and specialized signaling pathways. Binds
CC to a large number of partners, usually by recognition of a
CC phosphoserine or phosphothreonine motif. Binding generally results
CC in the modulation of the activity of the binding partner.
CC -!- SUBUNIT: Interacts with CDK16 and BSPRY (By similarity). Interacts
CC with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity).
CC Interacts with MLF1 (phosphorylated form); the interaction retains
CC it in the cytoplasm (By similarity). Interacts with Thr-
CC phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By
CC similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and
CC hetero-dimerization is inhibited by phosphorylation on Ser-58.
CC Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with
CC Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts
CC with BAX; the interaction occurs in the cytoplasm. Under stress
CC conditions, MAPK8-mediated phosphorylation releases BAX to
CC mitochondria. Interacts with phosphorylated RAF1; the interaction
CC is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts
CC with TP53; the interaction enhances p53 transcriptional activity.
CC The Ser-58 phosphorylated form inhibits this interaction and p53
CC transcriptional activity. Interacts with ABL1 (phosphorylated
CC form); the interaction retains ABL1 in the cytoplasm. Interacts
CC with PKA-phosphorylated AANAT; the interaction modulates AANAT
CC enzymatic activity by increasing affinity for arylalkylamines and
CC acetyl-CoA and protecting the enzyme from dephosphorylation and
CC proteasomal degradation. It may also prevent thiol-dependent
CC inactivation. Interacts with AKT1; the interaction phosphorylates
CC YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-347088, EBI-347088;
CC Q29495:AANAT (xeno); NbExp=3; IntAct=EBI-347088, EBI-446413;
CC P00519:ABL1; NbExp=2; IntAct=EBI-347088, EBI-375543;
CC P60709:ACTB; NbExp=3; IntAct=EBI-347088, EBI-353944;
CC Q9P0K1:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567236;
CC Q9P0K1-3:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567267;
CC P10398:ARAF; NbExp=3; IntAct=EBI-347088, EBI-365961;
CC Q92974:ARHGEF2; NbExp=2; IntAct=EBI-347088, EBI-302405;
CC P25705:ATP5A1; NbExp=3; IntAct=EBI-347088, EBI-351437;
CC P06576:ATP5B; NbExp=2; IntAct=EBI-347088, EBI-356231;
CC Q92934:BAD; NbExp=5; IntAct=EBI-347088, EBI-700771;
CC Q61337:Bad (xeno); NbExp=3; IntAct=EBI-347088, EBI-400328;
CC P15056:BRAF; NbExp=3; IntAct=EBI-347088, EBI-365980;
CC P62158:CALM3; NbExp=2; IntAct=EBI-347088, EBI-397435;
CC O00257-3:CBX4; NbExp=2; IntAct=EBI-347088, EBI-4392727;
CC P30304:CDC25A; NbExp=2; IntAct=EBI-347088, EBI-747671;
CC P30305:CDC25B; NbExp=4; IntAct=EBI-347088, EBI-1051746;
CC Q00537:CDK17; NbExp=2; IntAct=EBI-347088, EBI-624648;
CC Q07002:CDK18; NbExp=2; IntAct=EBI-347088, EBI-746238;
CC P23528:CFL1; NbExp=3; IntAct=EBI-347088, EBI-352733;
CC P31327:CPS1; NbExp=2; IntAct=EBI-347088, EBI-536811;
CC P67828:CSNK1A1 (xeno); NbExp=4; IntAct=EBI-347088, EBI-7540603;
CC P68104:EEF1A1; NbExp=2; IntAct=EBI-347088, EBI-352162;
CC P00533:EGFR; NbExp=4; IntAct=EBI-347088, EBI-297353;
CC P06733:ENO1; NbExp=2; IntAct=EBI-347088, EBI-353877;
CC Q16658:FSCN1; NbExp=3; IntAct=EBI-347088, EBI-351076;
CC P30793:GCH1; NbExp=4; IntAct=EBI-347088, EBI-958183;
CC P49841:GSK3B; NbExp=4; IntAct=EBI-347088, EBI-373586;
CC P56524:HDAC4; NbExp=5; IntAct=EBI-347088, EBI-308629;
CC Q9UQL6:HDAC5; NbExp=2; IntAct=EBI-347088, EBI-715576;
CC Q8WUI4:HDAC7; NbExp=3; IntAct=EBI-347088, EBI-1048378;
CC P0C0S8:HIST1H2AM; NbExp=2; IntAct=EBI-347088, EBI-1390628;
CC P68431:HIST1H3D; NbExp=3; IntAct=EBI-347088, EBI-79722;
CC P62805:HIST2H4B; NbExp=3; IntAct=EBI-347088, EBI-302023;
CC P07910:HNRNPC; NbExp=2; IntAct=EBI-347088, EBI-357966;
CC P04792:HSPB1; NbExp=2; IntAct=EBI-347088, EBI-352682;
CC Q02241:KIF23; NbExp=5; IntAct=EBI-347088, EBI-306852;
CC P02545:LMNA; NbExp=2; IntAct=EBI-347088, EBI-351935;
CC Q5S007:LRRK2; NbExp=4; IntAct=EBI-347088, EBI-5323863;
CC Q99683:MAP3K5; NbExp=3; IntAct=EBI-347088, EBI-476263;
CC P10636:MAPT; NbExp=8; IntAct=EBI-347088, EBI-366182;
CC P10636-3:MAPT; NbExp=9; IntAct=EBI-347088, EBI-7145070;
CC P29172:MAPT (xeno); NbExp=2; IntAct=EBI-347088, EBI-7291149;
CC Q7KZI7:MARK2; NbExp=6; IntAct=EBI-347088, EBI-516560;
CC P27448:MARK3; NbExp=9; IntAct=EBI-347088, EBI-707595;
CC Q9NYL2:MLTK; NbExp=4; IntAct=EBI-347088, EBI-602273;
CC P19338:NCL; NbExp=2; IntAct=EBI-347088, EBI-346967;
CC P06748:NPM1; NbExp=2; IntAct=EBI-347088, EBI-78579;
CC Q8TEW0:PARD3; NbExp=4; IntAct=EBI-347088, EBI-81968;
CC Q02156:PRKCE; NbExp=5; IntAct=EBI-347088, EBI-706254;
CC O14744:PRMT5; NbExp=2; IntAct=EBI-347088, EBI-351098;
CC P04049:RAF1; NbExp=13; IntAct=EBI-347088, EBI-365996;
CC Q8NFH8-2:REPS2; NbExp=2; IntAct=EBI-347088, EBI-8029141;
CC P61587:RND3; NbExp=11; IntAct=EBI-347088, EBI-1111534;
CC P61588:Rnd3 (xeno); NbExp=3; IntAct=EBI-347088, EBI-6930266;
CC P23396:RPS3; NbExp=2; IntAct=EBI-347088, EBI-351193;
CC P31947:SFN; NbExp=2; IntAct=EBI-347088, EBI-476295;
CC P57059:SIK1; NbExp=4; IntAct=EBI-347088, EBI-1181640;
CC Q9Y2K2:SIK3; NbExp=5; IntAct=EBI-347088, EBI-1181460;
CC O94875:SORBS2; NbExp=2; IntAct=EBI-347088, EBI-311323;
CC Q15831:STK11; NbExp=6; IntAct=EBI-347088, EBI-306838;
CC O00506:STK25; NbExp=2; IntAct=EBI-347088, EBI-618295;
CC P36897:TGFBR1; NbExp=4; IntAct=EBI-347088, EBI-1027557;
CC P04637:TP53; NbExp=2; IntAct=EBI-347088, EBI-366083;
CC P49815:TSC2; NbExp=8; IntAct=EBI-347088, EBI-396587;
CC P55072:VCP; NbExp=2; IntAct=EBI-347088, EBI-355164;
CC P08670:VIM; NbExp=2; IntAct=EBI-347088, EBI-353844;
CC P30291:WEE1; NbExp=3; IntAct=EBI-347088, EBI-914695;
CC P46937:YAP1; NbExp=3; IntAct=EBI-347088, EBI-1044059;
CC P62258:YWHAE; NbExp=5; IntAct=EBI-347088, EBI-356498;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Located to stage
CC I to stage IV melanosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63104-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P63104-2; Sequence=VSP_047505;
CC Note=No experimental confirmation available;
CC -!- PTM: The delta, brain-specific form differs from the zeta form in
CC being phosphorylated (By similarity). Phosphorylation on Ser-184
CC by MAPK8; promotes dissociation of BAX and translocation of BAX to
CC mitochondria. Phosphorylation on Thr-232; inhibits binding of
CC RAF1. Phosphorylated on Ser-58 by PKA and protein kinase C delta
CC type catalytic subunit in a sphingosine-dependent fashion.
CC Phosphorylation on Ser-58 by PKA; disrupts homodimerization and
CC heterodimerization with YHAE and TP53.
CC -!- SIMILARITY: Belongs to the 14-3-3 family.
CC -!- CAUTION: Was originally (PubMed:1577711) thought to have
CC phospholipase A2 activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH51814.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=AAH73141.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M86400; AAA36446.1; -; mRNA.
DR EMBL; U28964; AAC52052.1; -; mRNA.
DR EMBL; AK289945; BAF82634.1; -; mRNA.
DR EMBL; AK296902; BAH12451.1; -; mRNA.
DR EMBL; CH471060; EAW91823.1; -; Genomic_DNA.
DR EMBL; BC003623; AAH03623.3; -; mRNA.
DR EMBL; BC051814; AAH51814.1; ALT_INIT; mRNA.
DR EMBL; BC063824; AAH63824.2; -; mRNA.
DR EMBL; BC068456; AAH68456.2; -; mRNA.
DR EMBL; BC072426; AAH72426.2; -; mRNA.
DR EMBL; BC073141; AAH73141.1; ALT_INIT; mRNA.
DR EMBL; BC083508; AAH83508.2; -; mRNA.
DR EMBL; BC099904; AAH99904.1; -; mRNA.
DR EMBL; BC101483; AAI01484.1; -; mRNA.
DR EMBL; BC108281; AAI08282.1; -; mRNA.
DR EMBL; BC111951; AAI11952.1; -; mRNA.
DR PIR; A38246; PSHUAM.
DR RefSeq; NP_001129171.1; NM_001135699.1.
DR RefSeq; NP_001129172.1; NM_001135700.1.
DR RefSeq; NP_001129173.1; NM_001135701.1.
DR RefSeq; NP_001129174.1; NM_001135702.1.
DR RefSeq; NP_003397.1; NM_003406.3.
DR RefSeq; NP_663723.1; NM_145690.2.
DR RefSeq; XP_005251118.1; XM_005251061.1.
DR RefSeq; XP_005251119.1; XM_005251062.1.
DR RefSeq; XP_005251120.1; XM_005251063.1.
DR RefSeq; XP_005251121.1; XM_005251064.1.
DR UniGene; Hs.492407; -.
DR PDB; 1IB1; X-ray; 2.70 A; A/B/C/D=1-245.
DR PDB; 1QJA; X-ray; 2.00 A; A/B=1-245.
DR PDB; 1QJB; X-ray; 2.00 A; A/B=1-245.
DR PDB; 2C1J; X-ray; 2.60 A; A/B=1-245.
DR PDB; 2C1N; X-ray; 2.00 A; A/B=1-245.
DR PDB; 2O02; X-ray; 1.50 A; A/B=1-230.
DR PDB; 2WH0; X-ray; 2.25 A; A/B/C/D=1-245.
DR PDB; 3CU8; X-ray; 2.40 A; A/B=1-245.
DR PDB; 3NKX; X-ray; 2.40 A; A/B=1-245.
DR PDB; 3RDH; X-ray; 2.39 A; A/B/C/D=1-245.
DR PDB; 4BG6; X-ray; 2.30 A; A/B=1-245.
DR PDB; 4FJ3; X-ray; 1.95 A; A/B=1-230.
DR PDB; 4HKC; X-ray; 2.20 A; A=1-245.
DR PDB; 4IHL; X-ray; 2.20 A; A/B=1-230.
DR PDBsum; 1IB1; -.
DR PDBsum; 1QJA; -.
DR PDBsum; 1QJB; -.
DR PDBsum; 2C1J; -.
DR PDBsum; 2C1N; -.
DR PDBsum; 2O02; -.
DR PDBsum; 2WH0; -.
DR PDBsum; 3CU8; -.
DR PDBsum; 3NKX; -.
DR PDBsum; 3RDH; -.
DR PDBsum; 4BG6; -.
DR PDBsum; 4FJ3; -.
DR PDBsum; 4HKC; -.
DR PDBsum; 4IHL; -.
DR ProteinModelPortal; P63104; -.
DR SMR; P63104; 1-230.
DR DIP; DIP-563N; -.
DR IntAct; P63104; 514.
DR MINT; MINT-89071; -.
DR DrugBank; DB01381; Ginkgo biloba.
DR PhosphoSite; P63104; -.
DR DMDM; 52000887; -.
DR DOSAC-COBS-2DPAGE; P63104; -.
DR OGP; P63104; -.
DR UCD-2DPAGE; P63104; -.
DR PaxDb; P63104; -.
DR PRIDE; P63104; -.
DR DNASU; 7534; -.
DR Ensembl; ENST00000353245; ENSP00000309503; ENSG00000164924.
DR Ensembl; ENST00000395951; ENSP00000379281; ENSG00000164924.
DR Ensembl; ENST00000395953; ENSP00000379283; ENSG00000164924.
DR Ensembl; ENST00000395956; ENSP00000379286; ENSG00000164924.
DR Ensembl; ENST00000395957; ENSP00000379287; ENSG00000164924.
DR Ensembl; ENST00000395958; ENSP00000379288; ENSG00000164924.
DR Ensembl; ENST00000419477; ENSP00000395114; ENSG00000164924.
DR Ensembl; ENST00000457309; ENSP00000398599; ENSG00000164924.
DR Ensembl; ENST00000522542; ENSP00000430072; ENSG00000164924.
DR GeneID; 7534; -.
DR KEGG; hsa:7534; -.
DR UCSC; uc003yjv.2; human.
DR CTD; 7534; -.
DR GeneCards; GC08M101930; -.
DR HGNC; HGNC:12855; YWHAZ.
DR HPA; CAB005065; -.
DR MIM; 601288; gene.
DR neXtProt; NX_P63104; -.
DR PharmGKB; PA37444; -.
DR eggNOG; COG5040; -.
DR HOVERGEN; HBG050423; -.
DR InParanoid; P63104; -.
DR KO; K16197; -.
DR OrthoDB; EOG7HHWT3; -.
DR PhylomeDB; P63104; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; P63104; -.
DR ChiTaRS; YWHAZ; human.
DR EvolutionaryTrace; P63104; -.
DR GeneWiki; YWHAZ; -.
DR GenomeRNAi; 7534; -.
DR NextBio; 29475; -.
DR PRO; PR:P63104; -.
DR ArrayExpress; P63104; -.
DR Bgee; P63104; -.
DR Genevestigator; P63104; -.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl.
DR Gene3D; 1.20.190.20; -; 1.
DR InterPro; IPR000308; 14-3-3.
DR InterPro; IPR023409; 14-3-3_CS.
DR InterPro; IPR023410; 14-3-3_domain.
DR PANTHER; PTHR18860; PTHR18860; 1.
DR Pfam; PF00244; 14-3-3; 1.
DR PIRSF; PIRSF000868; 14-3-3; 1.
DR PRINTS; PR00305; 1433ZETA.
DR SMART; SM00101; 14_3_3; 1.
DR SUPFAM; SSF48445; SSF48445; 1.
DR PROSITE; PS00796; 1433_1; 1.
DR PROSITE; PS00797; 1433_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1 245 14-3-3 protein zeta/delta.
FT /FTId=PRO_0000058627.
FT SITE 56 56 Interaction with phosphoserine on
FT interacting protein (By similarity).
FT SITE 127 127 Interaction with phosphoserine on
FT interacting protein (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 3 3 N6-acetyllysine.
FT MOD_RES 58 58 Phosphoserine; by PKA and PKB/AKT1.
FT MOD_RES 68 68 N6-acetyllysine.
FT MOD_RES 184 184 Phosphoserine; by MAPK8.
FT MOD_RES 207 207 Phosphoserine.
FT MOD_RES 232 232 Phosphothreonine; by CK1.
FT VAR_SEQ 1 98 MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEER
FT NLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREY
FT REKIETELRDICNDVL -> MSQPCRKLWRHNYETSSCIEF
FT LK (in isoform 2).
FT /FTId=VSP_047505.
FT MUTAGEN 49 49 K->E: Loss of interaction with NOXA1.
FT MUTAGEN 58 58 S->A: Loss of sphingosine-activated PKA
FT phosphorylation. Promotes
FT homodimerization and heterodimerization
FT with YWHAE. Enhanced transcriptional
FT activity of P53.
FT MUTAGEN 58 58 S->E: Loss of homodimerization. Reduced
FT dimerization with YWHAE. Significantly
FT reduced interaction with P53. No
FT enhancement of P53 transcriptional
FT activity.
FT MUTAGEN 184 184 S->A: On DNA damage, loss of MAPK8-
FT mediated phosphorylation. Loss of binding
FT ABL1. Attenuates ABL1-mediated apoptosis.
FT No loss of interaction with BAX under
FT stress conditions. Inhibits translocation
FT of BAX to mitochondria.
FT CONFLICT 22 22 M -> V (in Ref. 5; AAH68456).
FT CONFLICT 136 136 D -> G (in Ref. 3; BAH12451).
FT HELIX 3 15
FT HELIX 19 31
FT HELIX 38 67
FT TURN 69 71
FT HELIX 76 103
FT HELIX 105 108
FT HELIX 112 131
FT HELIX 135 159
FT HELIX 165 180
FT HELIX 185 200
FT HELIX 201 205
FT TURN 208 210
FT HELIX 211 228
SQ SEQUENCE 245 AA; 27745 MW; D464DF2286BBFE60 CRC64;
MDKNELVQKA KLAEQAERYD DMAACMKSVT EQGAELSNEE RNLLSVAYKN VVGARRSSWR
VVSSIEQKTE GAEKKQQMAR EYREKIETEL RDICNDVLSL LEKFLIPNAS QAESKVFYLK
MKGDYYRYLA EVAAGDDKKG IVDQSQQAYQ EAFEISKKEM QPTHPIRLGL ALNFSVFYYE
ILNSPEKACS LAKTAFDEAI AELDTLSEES YKDSTLIMQL LRDNLTLWTS DTQGDEAEAG
EGGEN
//
MIM
601288
*RECORD*
*FIELD* NO
601288
*FIELD* TI
*601288 TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN,
ZETA ISOFORM; YWHAZ
read more;;BRAIN PROTEIN 14-3-3, ZETA ISOFORM;;
14-3-3-ZETA
*FIELD* TX
CLONING
The highly conserved 14-3-3 proteins are found in both plants and
mammals. Some have been shown to be involved in the activation of c-Raf
(164760) by their participation in the protein kinase C signaling
pathway (see 176960). Leffers et al. (1993) reported the cloning of
14-3-3-zeta. See YWHAH (113508) and YWHAB (601289).
Watanabe et al. (1994) isolated the rat zeta isoform of 14-3-3 from rat
brain. The deduced 245-amino acid protein shares high sequence homology
with other 14-3-3 subtypes. The zeta mRNA was widely expressed in
various gray matter brain regions, including the neocortex, hippocampus,
caudate-putamen, thalamus, cerebellar cortex, and several brain stem
nuclei. A human protein with phospholipase A2 activity was shown to be
the zeta subtype of the 14-3-3 protein (Zupan et al., 1992).
BIOCHEMICAL FEATURES
The 14-3-3 family of proteins mediates signal transduction by binding to
phosphoserine-containing proteins. Using phosphoserine-oriented peptide
libraries to probe all mammalian and yeast 14-3-3s, Yaffe et al. (1997)
identified 2 different binding motifs, RSXpSXP and RXY/FXpSXP, present
in nearly all known 14-3-3 binding proteins. The crystal structure of
YWHAZ complexed with the phosphoserine motif in polyoma middle-T was
determined to 2.6-angstrom resolution. The authors showed that the
14-3-3 dimer binds tightly to single molecules containing tandem repeats
of phosphoserine motifs, implicating bidentate association as a
signaling mechanism with molecules such as Raf, BAD (603167), and Cbl.
GENE FUNCTION
The binding of insulin (176730) to its receptor induces the
phosphorylation of the cytosolic substrates IRS1 (147545) and IRS2
(600797), which associate with several Src homology-2 (SH2)
domain-containing proteins. To identify unique IRS1-binding proteins,
Ogihara et al. (1997) screened a human heart cDNA expression library
with recombinant IRS1. They obtained 2 isoforms of the 14-3-3 protein
family, 14-3-3-zeta and -epsilon (YWHAE; 605066). 14-3-3 protein has
been shown to associate with IRS1 in L6 myotubes, HepG2 hepatoma cells,
Chinese hamster ovary cells, and bovine brain tissue. The amount of
14-3-3 protein associated with IRS1 was not affected by insulin
stimulation but was increased significantly by treatment with okadaic
acid, a potent serine/threonine phosphatase inhibitor. The authors
identified a putative 14-3-3 protein-binding site within the
phosphotyrosine-binding (PTB) domain of IRS1. Ogihara et al. (1997)
suggested that the association with 14-3-3 protein may play a role in
the regulation of insulin sensitivity by interrupting the association
between the insulin receptor and IRS1.
Using 2-hybrid experiments, Han et al. (1997) demonstrated interaction
between murine Ywhaz and the RAS-binding domain of RIN1 (605965).
Using in vitro pull-down assays, Powell et al. (2002) showed that
recombinant 14-3-3-zeta interacted directly with both recombinant and
endogenous protein kinase B (PKB, or AKT1; 164730) within embryonic
kidney cell lysates. They found that recombinant PKB phosphorylated
14-3-3-zeta in an in vitro kinase assay, and transfection of active PKB
into embryonic kidney cells resulted in phosphorylation of 14-3-3-zeta.
By mutation analysis, Powell et al. (2002) determined that the phosphate
acceptor was serine-58. They also showed that phosphorylation did not
result in 14-3-3-zeta dimerization.
Serotonin N-acetyltransferase (AANAT; 600950) controls daily changes in
the production and circulating levels of melatonin. Zheng et al. (2003)
studied the significance of the phosphorylation of AANAT using a
semisynthetic enzyme in which a nonhydrolyzable phosphoserine/threonine
mimetic, phosphonomethylenealanine (Pma), was incorporated at position
31 (AANAT-Pma31). The results of studies in which AANAT-Pma31 and
related analogs were injected into cells provided the first evidence
that threonine-31 phosphorylation controls AANAT stability in the
context of the intact cells by binding to 14-3-3-zeta protein. Zheng et
al. (2003) concluded that their findings established threonine-31
phosphorylation as an essential element in the intracellular regulation
of melatonin production.
By coimmunoprecipitation and tandem mass spectrometric analysis, Tian et
al. (2004) found that 14-3-3-zeta is a beta-catenin (116806)-interacting
protein. 14-3-3-zeta enhanced beta-catenin-dependent transcription by
stabilizing beta-catenin in the cytoplasm. Furthermore, 14-3-3-zeta
facilitated activation of beta-catenin by AKT and colocalized with
activated Akt in mouse intestinal stem cells. Tian et al. (2004)
proposed that AKT phosphorylates beta-catenin, leading to 14-3-3-zeta
binding and stabilization of beta catenin.
Li et al. (2010) found a significant association between amplification
of a region on chromosome 8q22 and de novo chemoresistance to
anthracyclines and metastatic recurrence in human breast cancer
(114480). Within this region, overexpression of both the YWHAZ and
LAPTM4B (613296) genes was found to correlate with the observations.
Knockdown of either of these genes using siRNA resulting in sensitivity
of tumor cells to anthracyclines. Extensive in vitro studies confirmed
the effect. Further studies indicated that LAPTM4B resulted in
sequestration of anthracycline and delayed entry into the nucleus,
whereas YWHAZ likely protected cells from apoptosis. The findings were
specific to anthracyclines.
Using proteomics and mass spectrometric analysis, Leivonen et al. (2011)
identified 14-3-3-zeta, SHMT2 (138450), and AKR1C2 (600450) as major
targets of microRNA-193B (MIR193B; 614734) in MCF-7 human breast cancer
cells. Cotransfection experiments confirmed that MIR193B downregulated
expression of reporter genes containing the 3-prime UTRs of SHMT2 or
YWHAZ or the 5-prime UTR of AKR1C2. Neutralization of MIR193B with
anti-MIR193B led to elevated SHMT2 and AKR1C2 protein levels, with
lesser upregulation of YWHAZ protein. Specific combinations of
knockdowns of these target genes via small interfering RNAs inhibited
growth in MCF-7 cells.
MAPPING
Tommerup and Leffers (1996) mapped the YWHAZ gene to chromosome
2p25.2-p25.1 by fluorescence in situ hybridization. However, Hartz
(2010) mapped the YWHAZ gene to chromosome 8q22.3 based on an alignment
of the YWHAZ sequence (GenBank GENBANK BC003623) with the genomic
sequence (GRCh37).
*FIELD* RF
1. Han, L. Wong, D.; Dhaka, A.; Afar, D.; White, M.; Xie, W.; Herschman,
H.; Witte, O.; Colicelli, J.: Protein binding and signaling properties
of RIN1 suggest a unique effector function. Proc. Nat. Acad. Sci. 94:
4954-4959, 1997.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 3/19/2010.
3. Leffers, H.; Madsen, P.; Rasmussen, H. H.; Honore, B.; Andersen,
A. H.; Walbum, E.; Vandekerckhove, J.; Celis, J. E.: 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. J. Molec. Biol. 231: 982-998, 1993.
4. Leivonen, S.-K.; Rokka, A.; Ostling, P.; Kohonen, P.; Corthals,
G. L.; Kallioniemi, O.; Perala, M.: Identification of miR-193b targets
in breast cancer cells and systems biological analysis of their functional
impact. Molec. Cell. Proteomics 10: 1Nov, 2011. Note: Electronic
Article.
5. Li, Y.; Zou, L.; Li, Q.; Haibe-Kains, B.; Tian, R; Li, Y.; Desmedt,
C.; Sotiriou, C.; Szallasi, Z; Iglehart, J. D.; Richardson, A. L.;
Wang, Z. C.: Amplification of LAPTM4B and YWHAZ contributes to chemotherapy
resistance and recurrence of breast cancer. Nature Med. 16: 214-218,
2010.
6. 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.: 14-3-3 protein binds to insulin receptor
substrate-1, one of the binding sites of which is in the phosphotyrosine
binding domain. J. Biol. Chem. 272: 25267-25274, 1997.
7. Powell, D. W.; Rane, M. J.; Chen, Q.; Singh, S.; McLeish, K. R.
: Identification of 14-3-3-zeta as a protein kinase B/Akt substrate. J.
Biol. Chem. 277: 21639-21642, 2002.
8. Tian, Q.; Feetham, M. C.; Tao, W. A.; He, X. C.; Li, L.; Aebersold,
R.; Hood, L.: Proteomic analysis identifies that 14-3-3-zeta interacts
with beta-catenin and facilitates its activation by Akt. Proc. Nat.
Acad. Sci. 101: 15370-15375, 2004.
9. Tommerup, N.; Leffers, H.: 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:
149-150, 1996.
10. Watanabe, M.; Isobe, T.; Ichimura, T.; Kuwano, R.; Takahashi,
Y.; Kondo, H.; Inoue, Y.: Molecular cloning of rat cDNAs for the
zeta and theta subtypes of 14-3-3 protein and differential distributions
of their mRNAs in the brain. Molec. Brain Res. 25: 113-121, 1994.
11. Yaffe, M. B.; Rittinger, K.; Volinia, S.; Caron, P. R.; Aitken,
A.; Leffers, H.; Gamblin, S. J.; Smerdon, S. J.; Cantley, L. C.:
The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91:
961-971, 1997.
12. Zheng, W.; Zhang, Z.; Ganguly, S.; Weller, J. L.; Klein, D. C.;
Cole, P. A.: Cellular stabilization of the melatonin rhythm enzyme
induced by nonhydrolyzable phosphonate incorporation. Nature Struct.
Biol. 10: 1054-1057, 2003.
13. Zupan, L. A.; Steffens, D. L.; Berry, C. A.; Landt, M.; Gross,
R. W.: Cloning and expression of a human 14-3-3 protein mediating
phospholipolysis. J. Biol. Chem. 267: 8707-8710, 1992.
*FIELD* CN
Patricia A. Hartz - updated: 07/20/2012
Patricia A. Hartz - updated: 3/19/2010
Cassandra L. Kniffin - updated: 3/9/2010
Patricia A. Hartz - updated: 11/17/2004
Ada Hamosh - updated: 1/8/2004
Patricia A. Hartz - updated: 8/19/2002
Dawn Watkins-Chow - updated: 5/25/2001
Patti M. Sherman - updated: 6/22/2000
Stylianos E. Antonarakis - updated: 2/20/1998
*FIELD* CD
Alan F. Scott: 6/3/1996
*FIELD* ED
mgross: 07/20/2012
mgross: 3/24/2010
terry: 3/19/2010
wwang: 3/17/2010
ckniffin: 3/9/2010
tkritzer: 2/22/2005
ckniffin: 2/7/2005
mgross: 11/17/2004
tkritzer: 1/12/2004
terry: 1/8/2004
mgross: 8/19/2002
carol: 5/25/2001
mcapotos: 6/23/2000
psherman: 6/22/2000
terry: 11/13/1998
alopez: 10/20/1998
terry: 6/1/1998
dholmes: 2/20/1998
jenny: 4/8/1997
terry: 6/3/1996
mark: 6/3/1996
*RECORD*
*FIELD* NO
601288
*FIELD* TI
*601288 TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN,
ZETA ISOFORM; YWHAZ
read more;;BRAIN PROTEIN 14-3-3, ZETA ISOFORM;;
14-3-3-ZETA
*FIELD* TX
CLONING
The highly conserved 14-3-3 proteins are found in both plants and
mammals. Some have been shown to be involved in the activation of c-Raf
(164760) by their participation in the protein kinase C signaling
pathway (see 176960). Leffers et al. (1993) reported the cloning of
14-3-3-zeta. See YWHAH (113508) and YWHAB (601289).
Watanabe et al. (1994) isolated the rat zeta isoform of 14-3-3 from rat
brain. The deduced 245-amino acid protein shares high sequence homology
with other 14-3-3 subtypes. The zeta mRNA was widely expressed in
various gray matter brain regions, including the neocortex, hippocampus,
caudate-putamen, thalamus, cerebellar cortex, and several brain stem
nuclei. A human protein with phospholipase A2 activity was shown to be
the zeta subtype of the 14-3-3 protein (Zupan et al., 1992).
BIOCHEMICAL FEATURES
The 14-3-3 family of proteins mediates signal transduction by binding to
phosphoserine-containing proteins. Using phosphoserine-oriented peptide
libraries to probe all mammalian and yeast 14-3-3s, Yaffe et al. (1997)
identified 2 different binding motifs, RSXpSXP and RXY/FXpSXP, present
in nearly all known 14-3-3 binding proteins. The crystal structure of
YWHAZ complexed with the phosphoserine motif in polyoma middle-T was
determined to 2.6-angstrom resolution. The authors showed that the
14-3-3 dimer binds tightly to single molecules containing tandem repeats
of phosphoserine motifs, implicating bidentate association as a
signaling mechanism with molecules such as Raf, BAD (603167), and Cbl.
GENE FUNCTION
The binding of insulin (176730) to its receptor induces the
phosphorylation of the cytosolic substrates IRS1 (147545) and IRS2
(600797), which associate with several Src homology-2 (SH2)
domain-containing proteins. To identify unique IRS1-binding proteins,
Ogihara et al. (1997) screened a human heart cDNA expression library
with recombinant IRS1. They obtained 2 isoforms of the 14-3-3 protein
family, 14-3-3-zeta and -epsilon (YWHAE; 605066). 14-3-3 protein has
been shown to associate with IRS1 in L6 myotubes, HepG2 hepatoma cells,
Chinese hamster ovary cells, and bovine brain tissue. The amount of
14-3-3 protein associated with IRS1 was not affected by insulin
stimulation but was increased significantly by treatment with okadaic
acid, a potent serine/threonine phosphatase inhibitor. The authors
identified a putative 14-3-3 protein-binding site within the
phosphotyrosine-binding (PTB) domain of IRS1. Ogihara et al. (1997)
suggested that the association with 14-3-3 protein may play a role in
the regulation of insulin sensitivity by interrupting the association
between the insulin receptor and IRS1.
Using 2-hybrid experiments, Han et al. (1997) demonstrated interaction
between murine Ywhaz and the RAS-binding domain of RIN1 (605965).
Using in vitro pull-down assays, Powell et al. (2002) showed that
recombinant 14-3-3-zeta interacted directly with both recombinant and
endogenous protein kinase B (PKB, or AKT1; 164730) within embryonic
kidney cell lysates. They found that recombinant PKB phosphorylated
14-3-3-zeta in an in vitro kinase assay, and transfection of active PKB
into embryonic kidney cells resulted in phosphorylation of 14-3-3-zeta.
By mutation analysis, Powell et al. (2002) determined that the phosphate
acceptor was serine-58. They also showed that phosphorylation did not
result in 14-3-3-zeta dimerization.
Serotonin N-acetyltransferase (AANAT; 600950) controls daily changes in
the production and circulating levels of melatonin. Zheng et al. (2003)
studied the significance of the phosphorylation of AANAT using a
semisynthetic enzyme in which a nonhydrolyzable phosphoserine/threonine
mimetic, phosphonomethylenealanine (Pma), was incorporated at position
31 (AANAT-Pma31). The results of studies in which AANAT-Pma31 and
related analogs were injected into cells provided the first evidence
that threonine-31 phosphorylation controls AANAT stability in the
context of the intact cells by binding to 14-3-3-zeta protein. Zheng et
al. (2003) concluded that their findings established threonine-31
phosphorylation as an essential element in the intracellular regulation
of melatonin production.
By coimmunoprecipitation and tandem mass spectrometric analysis, Tian et
al. (2004) found that 14-3-3-zeta is a beta-catenin (116806)-interacting
protein. 14-3-3-zeta enhanced beta-catenin-dependent transcription by
stabilizing beta-catenin in the cytoplasm. Furthermore, 14-3-3-zeta
facilitated activation of beta-catenin by AKT and colocalized with
activated Akt in mouse intestinal stem cells. Tian et al. (2004)
proposed that AKT phosphorylates beta-catenin, leading to 14-3-3-zeta
binding and stabilization of beta catenin.
Li et al. (2010) found a significant association between amplification
of a region on chromosome 8q22 and de novo chemoresistance to
anthracyclines and metastatic recurrence in human breast cancer
(114480). Within this region, overexpression of both the YWHAZ and
LAPTM4B (613296) genes was found to correlate with the observations.
Knockdown of either of these genes using siRNA resulting in sensitivity
of tumor cells to anthracyclines. Extensive in vitro studies confirmed
the effect. Further studies indicated that LAPTM4B resulted in
sequestration of anthracycline and delayed entry into the nucleus,
whereas YWHAZ likely protected cells from apoptosis. The findings were
specific to anthracyclines.
Using proteomics and mass spectrometric analysis, Leivonen et al. (2011)
identified 14-3-3-zeta, SHMT2 (138450), and AKR1C2 (600450) as major
targets of microRNA-193B (MIR193B; 614734) in MCF-7 human breast cancer
cells. Cotransfection experiments confirmed that MIR193B downregulated
expression of reporter genes containing the 3-prime UTRs of SHMT2 or
YWHAZ or the 5-prime UTR of AKR1C2. Neutralization of MIR193B with
anti-MIR193B led to elevated SHMT2 and AKR1C2 protein levels, with
lesser upregulation of YWHAZ protein. Specific combinations of
knockdowns of these target genes via small interfering RNAs inhibited
growth in MCF-7 cells.
MAPPING
Tommerup and Leffers (1996) mapped the YWHAZ gene to chromosome
2p25.2-p25.1 by fluorescence in situ hybridization. However, Hartz
(2010) mapped the YWHAZ gene to chromosome 8q22.3 based on an alignment
of the YWHAZ sequence (GenBank GENBANK BC003623) with the genomic
sequence (GRCh37).
*FIELD* RF
1. Han, L. Wong, D.; Dhaka, A.; Afar, D.; White, M.; Xie, W.; Herschman,
H.; Witte, O.; Colicelli, J.: Protein binding and signaling properties
of RIN1 suggest a unique effector function. Proc. Nat. Acad. Sci. 94:
4954-4959, 1997.
2. Hartz, P. A.: Personal Communication. Baltimore, Md. 3/19/2010.
3. Leffers, H.; Madsen, P.; Rasmussen, H. H.; Honore, B.; Andersen,
A. H.; Walbum, E.; Vandekerckhove, J.; Celis, J. E.: 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. J. Molec. Biol. 231: 982-998, 1993.
4. Leivonen, S.-K.; Rokka, A.; Ostling, P.; Kohonen, P.; Corthals,
G. L.; Kallioniemi, O.; Perala, M.: Identification of miR-193b targets
in breast cancer cells and systems biological analysis of their functional
impact. Molec. Cell. Proteomics 10: 1Nov, 2011. Note: Electronic
Article.
5. Li, Y.; Zou, L.; Li, Q.; Haibe-Kains, B.; Tian, R; Li, Y.; Desmedt,
C.; Sotiriou, C.; Szallasi, Z; Iglehart, J. D.; Richardson, A. L.;
Wang, Z. C.: Amplification of LAPTM4B and YWHAZ contributes to chemotherapy
resistance and recurrence of breast cancer. Nature Med. 16: 214-218,
2010.
6. 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.: 14-3-3 protein binds to insulin receptor
substrate-1, one of the binding sites of which is in the phosphotyrosine
binding domain. J. Biol. Chem. 272: 25267-25274, 1997.
7. Powell, D. W.; Rane, M. J.; Chen, Q.; Singh, S.; McLeish, K. R.
: Identification of 14-3-3-zeta as a protein kinase B/Akt substrate. J.
Biol. Chem. 277: 21639-21642, 2002.
8. Tian, Q.; Feetham, M. C.; Tao, W. A.; He, X. C.; Li, L.; Aebersold,
R.; Hood, L.: Proteomic analysis identifies that 14-3-3-zeta interacts
with beta-catenin and facilitates its activation by Akt. Proc. Nat.
Acad. Sci. 101: 15370-15375, 2004.
9. Tommerup, N.; Leffers, H.: 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:
149-150, 1996.
10. Watanabe, M.; Isobe, T.; Ichimura, T.; Kuwano, R.; Takahashi,
Y.; Kondo, H.; Inoue, Y.: Molecular cloning of rat cDNAs for the
zeta and theta subtypes of 14-3-3 protein and differential distributions
of their mRNAs in the brain. Molec. Brain Res. 25: 113-121, 1994.
11. Yaffe, M. B.; Rittinger, K.; Volinia, S.; Caron, P. R.; Aitken,
A.; Leffers, H.; Gamblin, S. J.; Smerdon, S. J.; Cantley, L. C.:
The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91:
961-971, 1997.
12. Zheng, W.; Zhang, Z.; Ganguly, S.; Weller, J. L.; Klein, D. C.;
Cole, P. A.: Cellular stabilization of the melatonin rhythm enzyme
induced by nonhydrolyzable phosphonate incorporation. Nature Struct.
Biol. 10: 1054-1057, 2003.
13. Zupan, L. A.; Steffens, D. L.; Berry, C. A.; Landt, M.; Gross,
R. W.: Cloning and expression of a human 14-3-3 protein mediating
phospholipolysis. J. Biol. Chem. 267: 8707-8710, 1992.
*FIELD* CN
Patricia A. Hartz - updated: 07/20/2012
Patricia A. Hartz - updated: 3/19/2010
Cassandra L. Kniffin - updated: 3/9/2010
Patricia A. Hartz - updated: 11/17/2004
Ada Hamosh - updated: 1/8/2004
Patricia A. Hartz - updated: 8/19/2002
Dawn Watkins-Chow - updated: 5/25/2001
Patti M. Sherman - updated: 6/22/2000
Stylianos E. Antonarakis - updated: 2/20/1998
*FIELD* CD
Alan F. Scott: 6/3/1996
*FIELD* ED
mgross: 07/20/2012
mgross: 3/24/2010
terry: 3/19/2010
wwang: 3/17/2010
ckniffin: 3/9/2010
tkritzer: 2/22/2005
ckniffin: 2/7/2005
mgross: 11/17/2004
tkritzer: 1/12/2004
terry: 1/8/2004
mgross: 8/19/2002
carol: 5/25/2001
mcapotos: 6/23/2000
psherman: 6/22/2000
terry: 11/13/1998
alopez: 10/20/1998
terry: 6/1/1998
dholmes: 2/20/1998
jenny: 4/8/1997
terry: 6/3/1996
mark: 6/3/1996