Full text data of YWHAH
YWHAH
(YWHA1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
14-3-3 protein eta (Protein AS1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
14-3-3 protein eta (Protein AS1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q04917
ID 1433F_HUMAN Reviewed; 246 AA.
AC Q04917;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 155.
DE RecName: Full=14-3-3 protein eta;
DE AltName: Full=Protein AS1;
GN Name=YWHAH; Synonyms=YWHA1;
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].
RC TISSUE=Brain;
RX PubMed=8218406; DOI=10.1016/0167-4781(93)90053-G;
RA Swanson K.D., Dhar M.S., Joshi J.G.;
RT "The human and bovine 14-3-3 eta protein mRNAs are highly conserved in
RT both their translated and untranslated regions.";
RL Biochim. Biophys. Acta 1216:145-148(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=1578511; DOI=10.1002/jnr.490310403;
RA Ichimura-Ohshima Y., Morii K., Ichimura T., Araki K., Takahashi Y.,
RA Isobe T., Minoshima S., Fukuyama R., Shimizu N., Kuwano R.;
RT "cDNA cloning and chromosome assignment of the gene for human brain
RT 14-3-3 protein eta chain.";
RL J. Neurosci. Res. 31:600-605(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Leffers H., Tommerup N., Celis J.E.;
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8561965; DOI=10.1007/BF02740697;
RA Muratake T., Hayashi S., Ichimura Y., Morii K., Kuwano R.,
RA Ichikawa T., Kumanishi T., Isobe T., Watanabe M., Kondo H.;
RT "The effect on methamphetamine on the mRNA level for 14.3.3 eta chain
RT in the human cultured cells.";
RL Mol. Neurobiol. 11:223-230(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8812417; DOI=10.1006/geno.1996.0426;
RA Muratake T., Hayashi S., Ichikawa T., Kumanishi T., Ichimura Y.,
RA Kuwano R., Isobe T., Wang Y., Minoshima S., Shimizu N., Takahashi Y.;
RT "Structural organization and chromosomal assignment of the human 14-3-
RT 3 eta chain gene (YWHAH).";
RL Genomics 36:63-69(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-225.
RC TISSUE=Keratinocyte;
RX PubMed=8515476; DOI=10.1006/jmbi.1993.1346;
RA Leffers H., Madsen P., Rasmussen H.H., Honore B., Andersen A.H.,
RA Walbum E., Vandekerckhove J., Celis J.E.;
RT "Molecular cloning and expression of the transformation sensitive
RT epithelial marker stratifin. A member of a protein family that has
RT been involved in the protein kinase C signalling pathway.";
RL J. Mol. Biol. 231:982-998(1993).
RN [10]
RP PROTEIN SEQUENCE OF 2-10.
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 [11]
RP PROTEIN SEQUENCE OF 2-10; 29-50; 62-69; 126-132; 144-155; 163-172 AND
RP 218-227, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V.;
RL Submitted (AUG-2005) to UniProtKB.
RN [12]
RP INTERACTION WITH AR; ESR1; ESR2; MC2R; NRIP1; NR3C1; PPARBP AND THRA.
RX PubMed=11266503; DOI=10.1210/me.15.4.501;
RA Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E.,
RA Gustafsson J.-A.;
RT "Regulation of glucocorticoid receptor activity by 14-3-3-dependent
RT intracellular relocalization of the corepressor RIP140.";
RL Mol. Endocrinol. 15:501-511(2001).
RN [13]
RP FUNCTION, AND INTERACTION WITH PDPK1.
RX PubMed=12177059; DOI=10.1074/jbc.M205141200;
RA Sato S., Fujita N., Tsuruo T.;
RT "Regulation of kinase activity of 3-phosphoinositide-dependent protein
RT kinase-1 by binding to 14-3-3.";
RL J. Biol. Chem. 277:39360-39367(2002).
RN [14]
RP INTERACTION WITH CDKN1B.
RX PubMed=14504289; DOI=10.1074/jbc.M306614200;
RA Fujita N., Sato S., Tsuruo T.;
RT "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein
RT S6 kinases promotes its binding to 14-3-3 and cytoplasmic
RT localization.";
RL J. Biol. Chem. 278:49254-49260(2003).
RN [15]
RP INTERACTION WITH ABL1, AND MASS SPECTROMETRY.
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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, 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 [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS), MASS SPECTROMETRY, INTERACTION
RP WITH PHOSPHOSERINE MOTIFS, AND SUBUNIT.
RX PubMed=17085597; DOI=10.1073/pnas.0605779103;
RA Yang X., Lee W.H., Sobott F., Papagrigoriou E., Robinson C.V.,
RA Grossmann J.G., Sundstroem M., Doyle D.A., Elkins J.M.;
RT "Structural basis for protein-protein interactions in the 14-3-3
RT protein family.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17237-17242(2006).
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 Negatively regulates the kinase activity of PDPK1.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with many nuclear
CC hormone receptors and cofactors including AR, ESR1, ESR2, MC2R,
CC NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated
CC form); the interaction retains it in the cytoplasm. Interacts with
CC ARHGEF28 and CDK16 (By similarity). Weakly interacts with CDKN1B.
CC Interacts with GAB2. Interacts with KCNK18 in a phosphorylation-
CC dependent manner. Interacts with SAMSN1 (By similarity). Interacts
CC with the 'Ser-241' phosphorylated form of PDPK1.
CC -!- INTERACTION:
CC Q96B36:AKT1S1; NbExp=3; IntAct=EBI-306940, EBI-720593;
CC Q8N5S9:CAMKK1; NbExp=5; IntAct=EBI-306940, EBI-6424030;
CC P30305:CDC25B; NbExp=3; IntAct=EBI-306940, EBI-1051746;
CC O94921:CDK14; NbExp=3; IntAct=EBI-306940, EBI-1043945;
CC P67828:CSNK1A1 (xeno); NbExp=8; IntAct=EBI-306940, EBI-7540603;
CC O60565:GREM1; NbExp=5; IntAct=EBI-306940, EBI-944395;
CC P56524:HDAC4; NbExp=3; IntAct=EBI-306940, EBI-308629;
CC Q14678-2:KANK1; NbExp=3; IntAct=EBI-306940, EBI-6173812;
CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-306940, EBI-5323863;
CC Q7KZI7:MARK2; NbExp=8; IntAct=EBI-306940, EBI-516560;
CC P27448:MARK3; NbExp=4; IntAct=EBI-306940, EBI-707595;
CC Q96L34:MARK4; NbExp=6; IntAct=EBI-306940, EBI-302319;
CC Q8TEW0:PARD3; NbExp=6; IntAct=EBI-306940, EBI-81968;
CC Q9NPB6:PARD6A; NbExp=2; IntAct=EBI-306940, EBI-81876;
CC Q9BYG5:PARD6B; NbExp=2; IntAct=EBI-306940, EBI-295391;
CC Q9BYG4:PARD6G; NbExp=2; IntAct=EBI-306940, EBI-295417;
CC P41743:PRKCI; NbExp=3; IntAct=EBI-306940, EBI-286199;
CC P04049:RAF1; NbExp=3; IntAct=EBI-306940, EBI-365996;
CC P61588:Rnd3 (xeno); NbExp=2; IntAct=EBI-306940, EBI-6930266;
CC -!- TISSUE SPECIFICITY: Expressed mainly in the brain and present in
CC other tissues albeit at lower levels.
CC -!- PTM: Phosphorylated on Ser-59 by protein kinase C delta type
CC catalytic subunit in a sphingosine-dependent fashion (By
CC similarity).
CC -!- SIMILARITY: Belongs to the 14-3-3 family.
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; L20422; AAA35483.1; -; mRNA.
DR EMBL; X80536; CAA56676.1; -; Genomic_DNA.
DR EMBL; X78138; CAA55017.1; -; mRNA.
DR EMBL; X57345; CAA40620.1; -; mRNA.
DR EMBL; D78577; BAA11418.1; -; Genomic_DNA.
DR EMBL; S80794; AAB36036.1; -; mRNA.
DR EMBL; CR456612; CAG30498.1; -; mRNA.
DR EMBL; Z82248; CAB05112.1; -; Genomic_DNA.
DR EMBL; BC003047; AAH03047.1; -; mRNA.
DR PIR; S34756; S34756.
DR PIR; S38509; S38509.
DR PIR; S38532; S38532.
DR RefSeq; NP_003396.1; NM_003405.3.
DR UniGene; Hs.226755; -.
DR PDB; 2C63; X-ray; 2.15 A; A/B/C/D=1-246.
DR PDB; 2C74; X-ray; 2.70 A; A/B=1-246.
DR PDBsum; 2C63; -.
DR PDBsum; 2C74; -.
DR ProteinModelPortal; Q04917; -.
DR SMR; Q04917; 3-235.
DR DIP; DIP-27566N; -.
DR IntAct; Q04917; 140.
DR MINT; MINT-124456; -.
DR STRING; 9606.ENSP00000248975; -.
DR PhosphoSite; Q04917; -.
DR DMDM; 1345593; -.
DR PaxDb; Q04917; -.
DR PeptideAtlas; Q04917; -.
DR PRIDE; Q04917; -.
DR DNASU; 7533; -.
DR Ensembl; ENST00000248975; ENSP00000248975; ENSG00000128245.
DR GeneID; 7533; -.
DR KEGG; hsa:7533; -.
DR UCSC; uc003alz.3; human.
DR CTD; 7533; -.
DR GeneCards; GC22P032340; -.
DR HGNC; HGNC:12853; YWHAH.
DR HPA; CAB025918; -.
DR MIM; 113508; gene.
DR neXtProt; NX_Q04917; -.
DR PharmGKB; PA37442; -.
DR eggNOG; COG5040; -.
DR HOGENOM; HOG000240379; -.
DR HOVERGEN; HBG050423; -.
DR InParanoid; Q04917; -.
DR KO; K16198; -.
DR OMA; ESSEAAY; -.
DR OrthoDB; EOG7HHWT3; -.
DR PhylomeDB; Q04917; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; Q04917; -.
DR ChiTaRS; YWHAH; human.
DR EvolutionaryTrace; Q04917; -.
DR GeneWiki; YWHAH; -.
DR GenomeRNAi; 7533; -.
DR NextBio; 29471; -.
DR PRO; PR:Q04917; -.
DR ArrayExpress; Q04917; -.
DR Bgee; Q04917; -.
DR CleanEx; HS_YWHAH; -.
DR Genevestigator; Q04917; -.
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:0014704; C:intercalated disc; IC:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISS:UniProtKB.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:BHF-UCL.
DR GO; GO:0006713; P:glucocorticoid catabolic process; IDA:UniProtKB.
DR GO; GO:0042921; P:glucocorticoid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0086010; P:membrane depolarization involved in regulation of action potential; IDA:BHF-UCL.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
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; Complete proteome;
KW Direct protein sequencing; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 246 14-3-3 protein eta.
FT /FTId=PRO_0000058623.
FT SITE 57 57 Interaction with phosphoserine on
FT interacting protein.
FT SITE 132 132 Interaction with phosphoserine on
FT interacting protein.
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 25 25 Phosphoserine.
FT MOD_RES 59 59 Phosphoserine (By similarity).
FT CONFLICT 144 144 N -> T (in Ref. 9; CAA40620).
FT CONFLICT 157 157 A -> G (in Ref. 1; AAA35483).
FT CONFLICT 237 237 Q -> L (in Ref. 1; AAA35483).
FT HELIX 4 16
FT HELIX 20 31
FT HELIX 39 73
FT HELIX 76 106
FT TURN 107 111
FT HELIX 117 137
FT HELIX 140 164
FT HELIX 170 185
FT HELIX 190 206
FT HELIX 207 210
FT TURN 213 215
FT HELIX 216 234
SQ SEQUENCE 246 AA; 28219 MW; D70FBC100C45D6E5 CRC64;
MGDREQLLQR ARLAEQAERY DDMASAMKAV TELNEPLSNE DRNLLSVAYK NVVGARRSSW
RVISSIEQKT MADGNEKKLE KVKAYREKIE KELETVCNDV LSLLDKFLIK NCNDFQYESK
VFYLKMKGDY YRYLAEVASG EKKNSVVEAS EAAYKEAFEI SKEQMQPTHP IRLGLALNFS
VFYYEIQNAP EQACLLAKQA FDDAIAELDT LNEDSYKDST LIMQLLRDNL TLWTSDQQDE
EAGEGN
//
ID 1433F_HUMAN Reviewed; 246 AA.
AC Q04917;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 155.
DE RecName: Full=14-3-3 protein eta;
DE AltName: Full=Protein AS1;
GN Name=YWHAH; Synonyms=YWHA1;
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].
RC TISSUE=Brain;
RX PubMed=8218406; DOI=10.1016/0167-4781(93)90053-G;
RA Swanson K.D., Dhar M.S., Joshi J.G.;
RT "The human and bovine 14-3-3 eta protein mRNAs are highly conserved in
RT both their translated and untranslated regions.";
RL Biochim. Biophys. Acta 1216:145-148(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=1578511; DOI=10.1002/jnr.490310403;
RA Ichimura-Ohshima Y., Morii K., Ichimura T., Araki K., Takahashi Y.,
RA Isobe T., Minoshima S., Fukuyama R., Shimizu N., Kuwano R.;
RT "cDNA cloning and chromosome assignment of the gene for human brain
RT 14-3-3 protein eta chain.";
RL J. Neurosci. Res. 31:600-605(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Leffers H., Tommerup N., Celis J.E.;
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8561965; DOI=10.1007/BF02740697;
RA Muratake T., Hayashi S., Ichimura Y., Morii K., Kuwano R.,
RA Ichikawa T., Kumanishi T., Isobe T., Watanabe M., Kondo H.;
RT "The effect on methamphetamine on the mRNA level for 14.3.3 eta chain
RT in the human cultured cells.";
RL Mol. Neurobiol. 11:223-230(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8812417; DOI=10.1006/geno.1996.0426;
RA Muratake T., Hayashi S., Ichikawa T., Kumanishi T., Ichimura Y.,
RA Kuwano R., Isobe T., Wang Y., Minoshima S., Shimizu N., Takahashi Y.;
RT "Structural organization and chromosomal assignment of the human 14-3-
RT 3 eta chain gene (YWHAH).";
RL Genomics 36:63-69(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-225.
RC TISSUE=Keratinocyte;
RX PubMed=8515476; DOI=10.1006/jmbi.1993.1346;
RA Leffers H., Madsen P., Rasmussen H.H., Honore B., Andersen A.H.,
RA Walbum E., Vandekerckhove J., Celis J.E.;
RT "Molecular cloning and expression of the transformation sensitive
RT epithelial marker stratifin. A member of a protein family that has
RT been involved in the protein kinase C signalling pathway.";
RL J. Mol. Biol. 231:982-998(1993).
RN [10]
RP PROTEIN SEQUENCE OF 2-10.
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 [11]
RP PROTEIN SEQUENCE OF 2-10; 29-50; 62-69; 126-132; 144-155; 163-172 AND
RP 218-227, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V.;
RL Submitted (AUG-2005) to UniProtKB.
RN [12]
RP INTERACTION WITH AR; ESR1; ESR2; MC2R; NRIP1; NR3C1; PPARBP AND THRA.
RX PubMed=11266503; DOI=10.1210/me.15.4.501;
RA Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E.,
RA Gustafsson J.-A.;
RT "Regulation of glucocorticoid receptor activity by 14-3-3-dependent
RT intracellular relocalization of the corepressor RIP140.";
RL Mol. Endocrinol. 15:501-511(2001).
RN [13]
RP FUNCTION, AND INTERACTION WITH PDPK1.
RX PubMed=12177059; DOI=10.1074/jbc.M205141200;
RA Sato S., Fujita N., Tsuruo T.;
RT "Regulation of kinase activity of 3-phosphoinositide-dependent protein
RT kinase-1 by binding to 14-3-3.";
RL J. Biol. Chem. 277:39360-39367(2002).
RN [14]
RP INTERACTION WITH CDKN1B.
RX PubMed=14504289; DOI=10.1074/jbc.M306614200;
RA Fujita N., Sato S., Tsuruo T.;
RT "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein
RT S6 kinases promotes its binding to 14-3-3 and cytoplasmic
RT localization.";
RL J. Biol. Chem. 278:49254-49260(2003).
RN [15]
RP INTERACTION WITH ABL1, AND MASS SPECTROMETRY.
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 [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, 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 [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS), MASS SPECTROMETRY, INTERACTION
RP WITH PHOSPHOSERINE MOTIFS, AND SUBUNIT.
RX PubMed=17085597; DOI=10.1073/pnas.0605779103;
RA Yang X., Lee W.H., Sobott F., Papagrigoriou E., Robinson C.V.,
RA Grossmann J.G., Sundstroem M., Doyle D.A., Elkins J.M.;
RT "Structural basis for protein-protein interactions in the 14-3-3
RT protein family.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17237-17242(2006).
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 Negatively regulates the kinase activity of PDPK1.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with many nuclear
CC hormone receptors and cofactors including AR, ESR1, ESR2, MC2R,
CC NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated
CC form); the interaction retains it in the cytoplasm. Interacts with
CC ARHGEF28 and CDK16 (By similarity). Weakly interacts with CDKN1B.
CC Interacts with GAB2. Interacts with KCNK18 in a phosphorylation-
CC dependent manner. Interacts with SAMSN1 (By similarity). Interacts
CC with the 'Ser-241' phosphorylated form of PDPK1.
CC -!- INTERACTION:
CC Q96B36:AKT1S1; NbExp=3; IntAct=EBI-306940, EBI-720593;
CC Q8N5S9:CAMKK1; NbExp=5; IntAct=EBI-306940, EBI-6424030;
CC P30305:CDC25B; NbExp=3; IntAct=EBI-306940, EBI-1051746;
CC O94921:CDK14; NbExp=3; IntAct=EBI-306940, EBI-1043945;
CC P67828:CSNK1A1 (xeno); NbExp=8; IntAct=EBI-306940, EBI-7540603;
CC O60565:GREM1; NbExp=5; IntAct=EBI-306940, EBI-944395;
CC P56524:HDAC4; NbExp=3; IntAct=EBI-306940, EBI-308629;
CC Q14678-2:KANK1; NbExp=3; IntAct=EBI-306940, EBI-6173812;
CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-306940, EBI-5323863;
CC Q7KZI7:MARK2; NbExp=8; IntAct=EBI-306940, EBI-516560;
CC P27448:MARK3; NbExp=4; IntAct=EBI-306940, EBI-707595;
CC Q96L34:MARK4; NbExp=6; IntAct=EBI-306940, EBI-302319;
CC Q8TEW0:PARD3; NbExp=6; IntAct=EBI-306940, EBI-81968;
CC Q9NPB6:PARD6A; NbExp=2; IntAct=EBI-306940, EBI-81876;
CC Q9BYG5:PARD6B; NbExp=2; IntAct=EBI-306940, EBI-295391;
CC Q9BYG4:PARD6G; NbExp=2; IntAct=EBI-306940, EBI-295417;
CC P41743:PRKCI; NbExp=3; IntAct=EBI-306940, EBI-286199;
CC P04049:RAF1; NbExp=3; IntAct=EBI-306940, EBI-365996;
CC P61588:Rnd3 (xeno); NbExp=2; IntAct=EBI-306940, EBI-6930266;
CC -!- TISSUE SPECIFICITY: Expressed mainly in the brain and present in
CC other tissues albeit at lower levels.
CC -!- PTM: Phosphorylated on Ser-59 by protein kinase C delta type
CC catalytic subunit in a sphingosine-dependent fashion (By
CC similarity).
CC -!- SIMILARITY: Belongs to the 14-3-3 family.
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; L20422; AAA35483.1; -; mRNA.
DR EMBL; X80536; CAA56676.1; -; Genomic_DNA.
DR EMBL; X78138; CAA55017.1; -; mRNA.
DR EMBL; X57345; CAA40620.1; -; mRNA.
DR EMBL; D78577; BAA11418.1; -; Genomic_DNA.
DR EMBL; S80794; AAB36036.1; -; mRNA.
DR EMBL; CR456612; CAG30498.1; -; mRNA.
DR EMBL; Z82248; CAB05112.1; -; Genomic_DNA.
DR EMBL; BC003047; AAH03047.1; -; mRNA.
DR PIR; S34756; S34756.
DR PIR; S38509; S38509.
DR PIR; S38532; S38532.
DR RefSeq; NP_003396.1; NM_003405.3.
DR UniGene; Hs.226755; -.
DR PDB; 2C63; X-ray; 2.15 A; A/B/C/D=1-246.
DR PDB; 2C74; X-ray; 2.70 A; A/B=1-246.
DR PDBsum; 2C63; -.
DR PDBsum; 2C74; -.
DR ProteinModelPortal; Q04917; -.
DR SMR; Q04917; 3-235.
DR DIP; DIP-27566N; -.
DR IntAct; Q04917; 140.
DR MINT; MINT-124456; -.
DR STRING; 9606.ENSP00000248975; -.
DR PhosphoSite; Q04917; -.
DR DMDM; 1345593; -.
DR PaxDb; Q04917; -.
DR PeptideAtlas; Q04917; -.
DR PRIDE; Q04917; -.
DR DNASU; 7533; -.
DR Ensembl; ENST00000248975; ENSP00000248975; ENSG00000128245.
DR GeneID; 7533; -.
DR KEGG; hsa:7533; -.
DR UCSC; uc003alz.3; human.
DR CTD; 7533; -.
DR GeneCards; GC22P032340; -.
DR HGNC; HGNC:12853; YWHAH.
DR HPA; CAB025918; -.
DR MIM; 113508; gene.
DR neXtProt; NX_Q04917; -.
DR PharmGKB; PA37442; -.
DR eggNOG; COG5040; -.
DR HOGENOM; HOG000240379; -.
DR HOVERGEN; HBG050423; -.
DR InParanoid; Q04917; -.
DR KO; K16198; -.
DR OMA; ESSEAAY; -.
DR OrthoDB; EOG7HHWT3; -.
DR PhylomeDB; Q04917; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; Q04917; -.
DR ChiTaRS; YWHAH; human.
DR EvolutionaryTrace; Q04917; -.
DR GeneWiki; YWHAH; -.
DR GenomeRNAi; 7533; -.
DR NextBio; 29471; -.
DR PRO; PR:Q04917; -.
DR ArrayExpress; Q04917; -.
DR Bgee; Q04917; -.
DR CleanEx; HS_YWHAH; -.
DR Genevestigator; Q04917; -.
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:0014704; C:intercalated disc; IC:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISS:UniProtKB.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:BHF-UCL.
DR GO; GO:0006713; P:glucocorticoid catabolic process; IDA:UniProtKB.
DR GO; GO:0042921; P:glucocorticoid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0086010; P:membrane depolarization involved in regulation of action potential; IDA:BHF-UCL.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
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; Complete proteome;
KW Direct protein sequencing; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 246 14-3-3 protein eta.
FT /FTId=PRO_0000058623.
FT SITE 57 57 Interaction with phosphoserine on
FT interacting protein.
FT SITE 132 132 Interaction with phosphoserine on
FT interacting protein.
FT MOD_RES 2 2 N-acetylglycine.
FT MOD_RES 25 25 Phosphoserine.
FT MOD_RES 59 59 Phosphoserine (By similarity).
FT CONFLICT 144 144 N -> T (in Ref. 9; CAA40620).
FT CONFLICT 157 157 A -> G (in Ref. 1; AAA35483).
FT CONFLICT 237 237 Q -> L (in Ref. 1; AAA35483).
FT HELIX 4 16
FT HELIX 20 31
FT HELIX 39 73
FT HELIX 76 106
FT TURN 107 111
FT HELIX 117 137
FT HELIX 140 164
FT HELIX 170 185
FT HELIX 190 206
FT HELIX 207 210
FT TURN 213 215
FT HELIX 216 234
SQ SEQUENCE 246 AA; 28219 MW; D70FBC100C45D6E5 CRC64;
MGDREQLLQR ARLAEQAERY DDMASAMKAV TELNEPLSNE DRNLLSVAYK NVVGARRSSW
RVISSIEQKT MADGNEKKLE KVKAYREKIE KELETVCNDV LSLLDKFLIK NCNDFQYESK
VFYLKMKGDY YRYLAEVASG EKKNSVVEAS EAAYKEAFEI SKEQMQPTHP IRLGLALNFS
VFYYEIQNAP EQACLLAKQA FDDAIAELDT LNEDSYKDST LIMQLLRDNL TLWTSDQQDE
EAGEGN
//
MIM
113508
*RECORD*
*FIELD* NO
113508
*FIELD* TI
*113508 TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN,
ETA ISOFORM; YWHAH
read more;;BRAIN PROTEIN 14-3-3, ETA ISOFORM;;
TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN
1; YWHA1;;
14-3-3-ETA
*FIELD* TX
DESCRIPTION
Protein 14-3-3 is a protein kinase-dependent activator of tyrosine and
tryptophan hydroxylases (191290, 191060) and an endogenous inhibitor of
protein kinase C (176960). The 14-3-3 protein exists in several distinct
forms: e.g., beta (YWHAB; 601289), gamma (YWHAG; 605356), epsilon
(YWHAE; 605066), zeta (YWHAZ; 601288), theta (YWHAQ; 609009), sigma
(SFN; 601290), and eta (YWHAH).
CLONING
Ichimura-Ohshima et al. (1992) reported a cDNA clone of mRNA encoding
human 14-3-3 protein. The 1,730-nucleotide sequence of the cDNA
contained a 191-bp 5-prime noncoding region, the complete 738-bp coding
region, and an 801-bp 3-prime noncoding region with 3 canonical
polyadenylation signals. The eta chain encoded by the cDNA is a
246-amino acid polypeptide with a predicted molecular weight of 28,196.
The predicted amino acid sequence of the human 14-3-3 protein eta was
highly homologous to that of previously reported bovine and rat proteins
with only 2 amino acid differences. Northern blot analysis demonstrated
widespread expression of the eta chain in cultured cell lines derived
from various human tumors.
GENE STRUCTURE
Muratake et al. (1996) determined that the human YWHAH gene has 2 exons
separated by an intron of approximately 8 kb. Using S1 nuclease mapping,
primer extension, and RACE PCR, Muratake et al. (1996) identified the
transcription initiation site. They also identified several regulatory
element sequences, including CRE, in the 5-prime noncoding region.
Muratake et al. (1996) noted that the presence of a CRE binding element
may indicate that this gene is involved in brain responses to narcotics.
The authors also found changes in a 7-bp repeat sequence (GCCTGCA)
located in the noncoding region of exon 1 and they speculated that these
changes, or other changes in the sequence of this gene, may be
associated with neuropsychiatric disorders.
MAPPING
Ichimura-Ohshima et al. (1992) used spot blot hybridization analysis
with flow sorted chromosomes to show that the eta chain is located on
chromosome 22. Tommerup and Leffers (1996) mapped the YWHAH gene to
22q12 by fluorescence in situ hybridization (FISH). Muratake et al.
(1996) used FISH to refine the mapping of the YWHAH gene to
22q12.1-q13.1.
GENE FUNCTION
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 (601288) 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.
Simsek-Duran et al. (2004) found that a 14-3-3 protein from rodent brain
lysate bound phosphorylated residue ser413 of the Rim1 (606629) protein,
whereas it did not bind to nonphosphorylatable Rim1 mutants. Presynaptic
transfection with a dominant-negative 14-3-3-eta mutant protein, which
showed reduced binding to Rim1, inhibited mouse cerebellar long-term
potentiation (LTP). The authors concluded that 14-3-3 is a necessary
downstream component of the ser413-Rim1 pathway involved in presynaptic
LTP; however, they noted that the brain 14-3-3 isoform could not be
identified definitively as eta.
*FIELD* RF
1. Ichimura-Ohshima, Y.; Morii, K.; Ichimura, T.; Araki, K.; Takahashi,
Y.; Isobe, T.; Minoshima, S.; Fukuyama, R.; Shimizu, N.; Kuwano, R.
: cDNA cloning and chromosome assignment of the gene for human brain
14-3-3 protein eta chain. J. Neurosci. Res. 31: 600-605, 1992.
2. Muratake, T.; Hayashi, S.; Ichikawa, T.; Kumanishi, T.; Ichimura,
Y.; Kuwano, R.; Isobe, T.; Wang, Y.; Minoshima, S.; Shimizu, N.; Takahashi,
Y.: Structural organization and chromosomal assignment of the human
14-3-3-eta chain gene (YWHAH). Genomics 36: 63-69, 1996.
3. Simsek-Duran, F.; Linden, D. J.; Lonart, G.: Adapter protein 14-3-3
is required for a presynaptic form of LTP in the cerebellum. Nature
Neurosci. 7: 1296-1298, 2004.
4. 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.
5. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/8/2005
Stylianos E. Antonarakis - updated: 2/20/1998
Jennifer P. Macke - updated: 10/16/1996
Alan F. Scott - updated: 6/3/1996
*FIELD* CD
Victor A. McKusick: 7/1/1992
*FIELD* ED
tkritzer: 02/22/2005
ckniffin: 2/8/2005
mcapotos: 6/26/2000
mcapotos: 6/23/2000
terry: 11/13/1998
alopez: 10/20/1998
terry: 6/3/1998
dholmes: 2/20/1998
joanna: 6/5/1997
mark: 12/31/1996
carol: 10/16/1996
mark: 6/3/1996
carol: 1/26/1995
carol: 8/25/1992
carol: 7/1/1992
*RECORD*
*FIELD* NO
113508
*FIELD* TI
*113508 TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN,
ETA ISOFORM; YWHAH
read more;;BRAIN PROTEIN 14-3-3, ETA ISOFORM;;
TYROSINE 3-MONOOXYGENASE/TRYPTOPHAN 5-MONOOXYGENASE ACTIVATION PROTEIN
1; YWHA1;;
14-3-3-ETA
*FIELD* TX
DESCRIPTION
Protein 14-3-3 is a protein kinase-dependent activator of tyrosine and
tryptophan hydroxylases (191290, 191060) and an endogenous inhibitor of
protein kinase C (176960). The 14-3-3 protein exists in several distinct
forms: e.g., beta (YWHAB; 601289), gamma (YWHAG; 605356), epsilon
(YWHAE; 605066), zeta (YWHAZ; 601288), theta (YWHAQ; 609009), sigma
(SFN; 601290), and eta (YWHAH).
CLONING
Ichimura-Ohshima et al. (1992) reported a cDNA clone of mRNA encoding
human 14-3-3 protein. The 1,730-nucleotide sequence of the cDNA
contained a 191-bp 5-prime noncoding region, the complete 738-bp coding
region, and an 801-bp 3-prime noncoding region with 3 canonical
polyadenylation signals. The eta chain encoded by the cDNA is a
246-amino acid polypeptide with a predicted molecular weight of 28,196.
The predicted amino acid sequence of the human 14-3-3 protein eta was
highly homologous to that of previously reported bovine and rat proteins
with only 2 amino acid differences. Northern blot analysis demonstrated
widespread expression of the eta chain in cultured cell lines derived
from various human tumors.
GENE STRUCTURE
Muratake et al. (1996) determined that the human YWHAH gene has 2 exons
separated by an intron of approximately 8 kb. Using S1 nuclease mapping,
primer extension, and RACE PCR, Muratake et al. (1996) identified the
transcription initiation site. They also identified several regulatory
element sequences, including CRE, in the 5-prime noncoding region.
Muratake et al. (1996) noted that the presence of a CRE binding element
may indicate that this gene is involved in brain responses to narcotics.
The authors also found changes in a 7-bp repeat sequence (GCCTGCA)
located in the noncoding region of exon 1 and they speculated that these
changes, or other changes in the sequence of this gene, may be
associated with neuropsychiatric disorders.
MAPPING
Ichimura-Ohshima et al. (1992) used spot blot hybridization analysis
with flow sorted chromosomes to show that the eta chain is located on
chromosome 22. Tommerup and Leffers (1996) mapped the YWHAH gene to
22q12 by fluorescence in situ hybridization (FISH). Muratake et al.
(1996) used FISH to refine the mapping of the YWHAH gene to
22q12.1-q13.1.
GENE FUNCTION
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 (601288) 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.
Simsek-Duran et al. (2004) found that a 14-3-3 protein from rodent brain
lysate bound phosphorylated residue ser413 of the Rim1 (606629) protein,
whereas it did not bind to nonphosphorylatable Rim1 mutants. Presynaptic
transfection with a dominant-negative 14-3-3-eta mutant protein, which
showed reduced binding to Rim1, inhibited mouse cerebellar long-term
potentiation (LTP). The authors concluded that 14-3-3 is a necessary
downstream component of the ser413-Rim1 pathway involved in presynaptic
LTP; however, they noted that the brain 14-3-3 isoform could not be
identified definitively as eta.
*FIELD* RF
1. Ichimura-Ohshima, Y.; Morii, K.; Ichimura, T.; Araki, K.; Takahashi,
Y.; Isobe, T.; Minoshima, S.; Fukuyama, R.; Shimizu, N.; Kuwano, R.
: cDNA cloning and chromosome assignment of the gene for human brain
14-3-3 protein eta chain. J. Neurosci. Res. 31: 600-605, 1992.
2. Muratake, T.; Hayashi, S.; Ichikawa, T.; Kumanishi, T.; Ichimura,
Y.; Kuwano, R.; Isobe, T.; Wang, Y.; Minoshima, S.; Shimizu, N.; Takahashi,
Y.: Structural organization and chromosomal assignment of the human
14-3-3-eta chain gene (YWHAH). Genomics 36: 63-69, 1996.
3. Simsek-Duran, F.; Linden, D. J.; Lonart, G.: Adapter protein 14-3-3
is required for a presynaptic form of LTP in the cerebellum. Nature
Neurosci. 7: 1296-1298, 2004.
4. 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.
5. 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.
*FIELD* CN
Cassandra L. Kniffin - updated: 2/8/2005
Stylianos E. Antonarakis - updated: 2/20/1998
Jennifer P. Macke - updated: 10/16/1996
Alan F. Scott - updated: 6/3/1996
*FIELD* CD
Victor A. McKusick: 7/1/1992
*FIELD* ED
tkritzer: 02/22/2005
ckniffin: 2/8/2005
mcapotos: 6/26/2000
mcapotos: 6/23/2000
terry: 11/13/1998
alopez: 10/20/1998
terry: 6/3/1998
dholmes: 2/20/1998
joanna: 6/5/1997
mark: 12/31/1996
carol: 10/16/1996
mark: 6/3/1996
carol: 1/26/1995
carol: 8/25/1992
carol: 7/1/1992