Gene: [22q12/YWHAH] tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide; protein kinase C-dependent activator of tyrosine/tryptophan hydroxylase; brain protein 14-3-3, eta subtype; [YWHA1 AS1 ]

COM

 There are some discrepancies in various versions of this gene and its protein product, submitted to public databases by different authors (see 'Coding_region'). For more information on this protein family, see 'Summary' in FAM:BP1433/00.0. Entries describing particular members of the family are also available using the section 'Related_records'."

SUM

 <* > [14-3-3 ETA PROTEIN IS] is a homodimeric molecule which functions in the cytoplasm of brain cells; at lower levels, the protein can be also presented in other tissues. In neurons, it is axonally transported to the nerve terminals. BP1433E is probably a multifunctional regulator of the cell signaling processes mediated by some of protein kinases; for example, in the presence of Ca2+/calmodulin-dependent protein kinase II, it ACTIVATES tyrosine and tryptophan hydroxilases (see GEM:11p155/TH and GEM:11p1/TRPH, respectively); at the same time, the eta protein is an INHIBITOR of Ca2+/phospholipid-dependent protein kinase C (GEM:17q2/PRKCA). %----------------------------------------------------------------------- <* > [FIRST, ICHIMURA T &:1988] (Dept Chemistry, Faculty of Science, Tokyo Metropolitan University, Japan) resolved the BOVINE brain 14-3-3 proteins into seven polypeptide components by means of reversed-phase chromato- graphy and determined the amino acid sequence of one of these components (eta chain) by isolating its cDNA from a bovine cerebellum cDNA library. The eta-chain mRNA was 1.8 kb long (see gnb:J03868). The authors showed that this mRNA encodes a polypeptide of 246 amino acids, and this eta protein contains two structural regions distinguishable in their clearly different charge characteristics: the almost neutral aminoterminal region and the strongly acidic carboxyl-terminal one. The structural features of the eta polypeptide and its domain organization suggest that this 14-3-3 protein bind to the regulatory domain of the phosphorylated hydroxylase along its acidic carboxyl-terminal region and activates these enzymes by inducing their active conformation. %----------------------------------------------------------------------- <* > [USING NORTHERN BLOT EXPERIMENTS], Ichimura-Ohshima Y &:1992 (Mol Genet Lab, Niigata Univ, Japan) showed widespread expression of 14-3-3 eta in cultured cell lines derived from various human tumors. <* > [ACCORDING TO SWANSON KD &:1993] (Dept Biochemistry, University of Tennessee, Knoxville 37996), 14-3-3 proteins ACTIVATE tyrosine/tryptophan hydroxylases, INHIBIT protein kinase C, and possess phospholipase A2 activity in vitro. The authors isolated a cDNA clone from a human fetal brain cDNA library and found it to possess a high level of sequence identity with the bovine 14-3-3 eta protein cDNA both in the translated and untranslated regions. The cloned cDNA hybridized with two mRNAs, 1.9 and 3.5 kb. Northern blot experiments with polyA+RNA isolated from eight different human tissues showed that these mRNAs are expressed in many human tissues though the highest abundance of the eta mRNAs was seen in the brain. In addition, only the 1.9 kb mRNA species was detected in the fetal brain."

COD

 "<* TITLE:> {PRT= 246 aa (MW= 28218) derived_from cDNA= 1752?1761? bp}
<* SOURCES:>
<** REFER_1:> [Leffers H &:1993]
/ID: Leffers H, Madsen P, Rasmussen HH, Honore B, Andersen AH,
Walbum E, Vandekerckhove J, Celis JE;
'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 Mol Biol, 231, N4 (Jun 20), 982-998, 1993\
<*** CITED_in:> [EMBL]
/ID: emb:X57345^HSAS1MRNA| cDNA= 601 bp;
'Homo sapiens mRNA for AS1 protein'\
/Date: Jan-23-1991^Jul-19-1993\
/Submitted_by: Leffers H (Univ of Aahrus, Inst Medical Biochemistry,
Universitetsparken Bygn 170, DK 8000 Aahrus C, Denmark);
//date: Jan-23-1991\
/Note: This is only a part of the 14-3-3 eta sequence; its more com-
plete and corrected version was later submitted by the same author
(see 'REFER_2' below)\
<*** CITED_in:> [PROT_DB]
<**** RECORD_1:> [SwissPROT]
/ID: swp:Q04917^143F_HUMAN| prt= 199 aa (MW= 22826);
'human 14-3-3 protein eta (protein AS1)'\
/Date: Oct-01-1993^Feb-01-1994\
/Note: Accounting for this sequence was incomplete, the following
features need to be corrected:
'source 1..199 14-3-3 protein eta/AS1 (incomplete)
site 33 phosphorylation (putative)
site 38 phosphorylation (putative)\
/Duplicated_by: cbi:416556\
<**** RECORD_2:> [PIR]
/ID: pir:S34756^S29339^S34753ref| prt= 199 aa (MW= ?);
'?'\
/Date: Dec-31-1993^May-03-1994\
/Note: According to a PIR's remark, the protein is related to the
superfamily phospholipase A2 (acyl-enzyme intermediate-forming)\
%-----------------------------------------------------------------------
<** REFER_2:> [Lefers H &:1994, Unpubl]
/ID: Leffers H, Tommerup N, Celis JE;
'Characterisation and chromosomal localisation of the 14-3-3
subtypes from human normal keratinocytes';
Unpublished, 1994\
<*** CITED_in:> [EMBL]
/ID: emb:X78138^HSETARNA| cDNA= 1398 bp;
'Homo sapiens 14-3-3 eta subtype mRNA';
//note: clone as12-5 from keratinocytes\
/Date: Mar-14-1994\
/Submitted_by: Leffers H (Inst Medical Biochemistry; & Danish Centre
for Human Genome Research, Ole Worms Alle 170, Aarhus University,
8000 Aarhus C, Denmark);
//date: Mar-11-1994\
/Duplicated_by: cbi:460778-779\
<*** CITED_in:> [PIR]
/ID: pir:S42476| prt= 246 aa (MW= 28218);
'human 14-3-3 eta subtype protein'\
/Date: May-20-1994\
/Duplicated_by: cbi:542740\
%-----------------------------------------------------------------------
<** REFER_3:> [Ichimura-Ohshima Y &:1992]
/ID: 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, N4 (Apr), 600-605, 1992\
<*** CITED_in:> [EMBL]
/ID: emb:X80536^HS1433PR| cDNA= 1730 bp;
'Homo sapiens gene for 14-3-3 protein';
//note: from cerebral cortex\
/Date: Aug-18-1994\
/Duplicated_by: cbi:531589-590\
<*** CITED_in:> [PIR]
/ID: pir:S38509| prt= 246 aa (MW= 28218);
'human 14-3-3 protein eta chain'\
/Date: Feb-18-1994\
/Duplicated_by: cbi:481360\
%-----------------------------------------------------------------------
<** REFER_4:> [Swanson KD &:1992]
/ID: Swanson KD, Dhar MS, Joshi JG;
'The human and bovine 14-3-3 eta protein mRNAs are highly con-
served in both their translated and untranslated regions';
Biochim Biophys Acta, 1216, N1 (Oct 19), 145-148, 1993\
<*** CITED_in:> [GENBank]
/ID: gnb:L20422^HUM1433ACT| cDNA= 1562 bp;
'Human 14-3-3n protein mRNA, complete cds';
//note: from human fetus brain cDNA library\
/Date: Feb-25-1994\
/Duplicated_by: cbi:437362-363\
<*** CITED_in:> [PIR]
/ID: pir:S38532| prt= 246 aa (MW= 28189);
'human 14-3-3 protein eta chain'\
/Date: Feb-18-1994\
/Duplicated_by: cbi:481365\
%-----------------------------------------------------------------------
<** REFER_5:> [Genexpress G, 1995, Unpubl]
/ID: Genexpress_Genethon;
'?';
Unpublished\
<*** CITED_in:> [EMBL]
/ID: emb:F08031^HSC2OD081| cDNA(EST)= 308 bp;
'Homo sapiens partial cDNA sequence (clone c-2od08)';
//note_1: from 3-month-old muscular atrophy patient; female
infant brain cDNA (provider: B.Soares, Psychiatry Dept,
Columbia University, N.Y., USA);
//note_2: Genexpress sequence ID: y1c-2od08\
/Date: Feb-17-1995\
/Submitted_by: Genethon (B.P. 60, 91002 Evry Cedex, France; e-mail:
genexpress@genethon.fr) & Genetique Moleculaire et Biologie du
developpement (CNRS UPR420 B.P. 8, 94801 Villejuif Cedex, France);
//date: Jan-19-1995\
/Duplicated_by: cbi:677535\
%-----------------------------------------------------------------------
<** REFER_6:> [Takeda J &:1993]
/ID: Takeda J, Yano H, Eng S, Zeng Y, Bell GI;
'A molecular inventory of human pancreatic islets: sequence
analysis of 1000 cDNA clones';
Hum Mol Genet, 2, N11 (Nov), 1793-1798, 1993;
//note: among the mentioned one thousand cDNA clones, there was
a 62 bp-sequence submitted to GenBank (see below); however,
the publication does not contain any particular reference to
the 14-3-3 eta gene product\
<*** CITED_in:> [GENBank]
/ID: gnb:T11377| cDNA(EST)= 62 bp;
'Homo sapiens cDNA clone hbc1323, 5'end';
//note: from normal adult human islets\
/Date: Nov-29-1993\
/Submitted_by: Bell GI & Takeda J (University of Chicago, 5841 South
Maryland Ave, MC1028, Chicago IL 60637; Tel: 312/702-9116;
Fax: 312/702-0271; e-mail: g-bell@uchicago.edu)\
/Note: This sequence contains two unidentified nucleotides (N) at the
positions #11 and #13, and one extra 'C' at the position #17 (pos:1
corresponds pos:1192 in gem:correct; see below):
|pos:1=tccatttaaa NcNagcCtga t=21_...|\
/Duplicated_by: cbi:391531\
%-----------------------------------------------------------------------
<* FEATURES:>
<** ALIGNMENT:> [Correspondences]
/Note: Numericals presented in columns of the Table below are numbers
of the aligned nucleotide positions in different versions of the
eta cDNA sequence: ref1 - Leffers H &:1993;
ref2 - Leffers H:1994;
ref3 - Ichimura-Ohshima Y &:1992;
ref4 - Swanson KD &:1993;
ref5 - Genexpress:1995;
ref6 - Takeda J &:1993;
gem:correct - verified regions of the sequence\
----------------------------------------------------------------------
//note: (ATG....coding_segment...)tga;
| |\
{gem:correct ? ? 1 97 106 182 229 536 782 844;
ref2:X78138 1 19 96 192 201 277 324 631 877 939;
ref3:X80536 - 1 87 183 192 268 315 622 868 930;
ref4:L20422 - - - 1 10 86 133 440 686 748;
ref1:X57345 - - - - - 1 48 355 601\
ref5:F08031 - - - - - - 1 308\}
%-----------
{gem:correct 1192 1252 1303 1644 1657\
ref2:X78138 1287 1347 1398\
ref3:X80536 1278 1338 1389 1730\
ref4:L20422 1098 1158 1208 1549 1562\
ref6:T11377 1 62\}
----------------------------------------------------------------------
%----------------------------------------------------------------------
<** ALIGNMENT:> [Conflicts & Corrections]
/Note_1: Numericals presented in columns of the Table below are numbers
of the aligned nucleotide positions in all six versions of the eta
cDNA sequence; positions with incorrect nucleotides are marked by '*'
while nucleotides occurring at the positions are presented by upper
case letters\
/Note_2: Some of the differences ref2, ref3, and ref4 cannot be verified,
particularly in 5'- and 3'-regions of the sequences, since all of the
sequences in question overlap each with others only partially (see
'SEQUENCE', Segment_1,4,6)\
----------------------------------------------------------------------
{gem:correct 536=ac 575=c 624=g 778=t 815=a 858=a 865=g;
%-----------
ref2:X78138 631=ac 670=c *719=T 873=t 910=a 953=a 960=g;
ref3:X80536 622=ac 661=c 710=g 864=t 901=a *944=G *951=A;
ref4:L20422 440=ac *479=G 528=g 682=t *719=T 762=a 769=g;
ref1:X57345 *355=CA 394=c 443=g *597=C - - -;
ref5:F08031 308=a\}
----------------------------------------------------------------
{gem:correct 896=a 916=__ 922=_ 996=g 1002=ga 1035=c 1076=a;
%-----------
ref2:X78138 991=a 1011=__ 1017=_ 1091=g 1097=ga 1130=c 1171=a;
ref3:X80536 982=a 1002=__ 1008=_ 1082=g 1088=ga 1121=c 1162=a;
ref4:L20422 *800=G *820=CA *826=A *903=_ *908=AG *941=A *982=_}
--------------------------------------------------------------------
{gem:correct 1095=_ 1157=a 1164=_ 1208=_ 1239=g 1255=t 1291=ct;
%-----------
ref2:X78138 1190=_ 1252=a 1259=_ 1303=_ 1334=g 1350=t *1386=GC;
ref3:X80536 1181=_ 1243=a 1250=_ 1294=_ 1325=g 1341=t 1377=ct;
ref4:L20422 *1000=A *1063=_ *1069=T 1114=_ *1145=T *1161=_ 1196=ct;
ref6:T11377 - - - *17=C 49=g}
----------------------------------------------------------------------
%----------------------------------------------------------------------
<** LANDMARKS:>
/Note_1: UTL, UnTransLated segment; CDS, CoDing Segment;
TLI, TransLation Initiation; TLT, TransLation Termination;
TTS, Transcription Termination Signal (polyA-signal);
TCT, TransCription Termination site (polyA-site);
pAseq, polyA-sequence\
/Note_2: The following features are indicated according to coordinates
of the 'gem:correct' sequence (see its definition above)\
{seg(-1..-95?86) = 5'-UTL(=95?86) //note: unverified_region;
seg(1..105) = 5'-UTL(=105) //note: verified_region;
seg(106..843) = CDS(=738) //note: for 246 amino acids;
pos:106 = TLI_1 //note: translation START;
seg(844..1657) = 3'-UTL(=814);
pos:844 = TLT_1 //note: translation STOP;
seg(1345..1350) = TTS_1? //note: putative;
seg(1606..1611) = TTS_2? //note: putative;
seg(1633..1638) = TTS_3? //note: putative;
pos:? = TCT_? //note: not described}
%----------------------------------------------------------------------
<* SEQUENCE:> [Total= 1752?1743 bp]
/Note: gem:correct - verified regions of the eta cDNA in question;
ref2 - Leffers-1994; ref3 - Ichimura-Ohshima-1992;
ref4 - Swanson-1993;
(discordant nucleotides are indicated by upper case letters;
the corresponding amino acids are marked by '*')\
%-------
<** Segment_1:> [5'-unverified= 95?86 bp]
%-------
ref2: 1=gcgcgcgagc cacagcgcCG GGGcgAgCcA Gcgagagggc _cgagcggcg=
#ref3: 1=__________ ________GA ATT..C.G.G C......... G.........=
ref2:50=gcgctgcctg cagcctgcaC gc________ tc_ggccggc cggcgagcca=
#ref3:33=.......... ........._ ..CTGCAGCC ..C....... ..........=
ref2:91=gtgGC=95_
#ref3:82=...CG=86_}
%-------
<** Segment_2:> [5'-verified & CDS, = 843 bp]
%-------
GEM : 1=cgtgcgcggc ggcggcctcc gcagcgaccg gggagcggac tgaccggcgg=
GEM : 51=gagggctagc gagccagcgg tgtgaggcgc gaggcgaggc cgagccGcga=
GEM : 101=gcgac=105_
pep : 1= M G D R E Q L L Q R A R L A E =
GEM : 106=atg ggg gac cgg gag cag ctg ctg cag cgg gcg cgg ctg gcc gag=
pep : 16= Q A E R Y D D M A S *A M K A V =
GEM : 151=cag gcg gag cgc tac gac gac atg gcc tcc gCt atg aag gcg gtg=
pep : 31= T E L N E P L S N E D R N L L =
GEM : 196=aca gag ctg aat gaa cct ctc tcc aat gaa gat cga aat ctc ctc=
pep : 46= S V A Y K N V V G A R R S S W =
GEM : 241=tct gtg gcc tac aag aat gtg gtt ggt gcc agg cga tct tcc tgg=
pep : 61= R V I S S I E Q K T M A D G N =
GEM : 286=agg gtc att agc agc att gag cag aaa acc atg gct gat gga aac=
pep : 76= E K K L E K V K A Y R E K I E =
GEM : 331=gaa aag aaa ttg gag aaa gtt aaa gct tac cgg gag aag att gag=
pep : 91= K E L E T V C N D V L S L L D =
GEM : 376=aag gag ctg gag aca gtt tgc aat gat gtc ctg tct ctg ctt gac=
pep :106= K F L I K N C N D F Q Y E S K =
GEM : 421=aag ttc ctg atc aag aac tgc aat gat ttc cag tat gag agc aag=
pep :121= V F Y L K M K G D Y Y R Y L A =
GEM : 466=gtg ttt tac ctg aaa atg aag ggt gat tac tac cgc tac tta gca=
pep :136= E V A S G E K K *N S V V E A S =
GEM : 511=gag gtc gct tct ggg gag aag aaa aAC agt gtg gtc gaa gct tct=
pep :151= E A A Y K E *A F E I S K E Q M =
GEM : 556=gaa gct gcc tac aag gaa gCc ttt gaa atc agc aaa gag cag atg=
pep :166= Q P T H P I R *L G L A L N F S =
GEM : 601=caa ccc acg cat ccc atc cgg ctG ggc ctg gcc ctc aac ttc tcc=
pep :181= V F Y Y E I Q N A P E Q A C L =
GEM : 646=gtg ttc tac tat gag atc cag aat gca cct gag caa gcc tgc ctc=
pep :196= L A K Q A F D D A I A E L D T =
GEM : 691=tta gcc aaa caa gcc ttc gat gat gcc ata gct gag ctg gac aca=
pep :211= L N E D S Y K D S T L I M Q *L =
GEM : 736=cta aac gag gat tcc tat aag gac tcc acg ctg atc atg cag Ttg=
pep :226= L R D N L T L W T S D *Q Q D E =
GEM : 781=ctg cga gac aac ctc acc ctc tgg acg agc gac cAg cag gat gaa=
pep :241= E A G E G N =246\
GEM : 826=gaa gca gga gaa ggc aac=843_
%-------
<** Segment_3:> [3'-UTL_verified= 518 bp]
%-------
GEM : 844=tgaagat=850_
GEM : 851=ccttcagAtc ccctGgccct tccttcaccc accaccccca tcatcAccga=
GEM : 901=ttcttccttg ccacaatcac taaatatcta gtgctaaacc tatctgtatt=
GEM : 951=ggcagcacag ctactcagat ctgcactcct gtctcttggg aagcaGtttc=
GEM :1001=aGAtaaatca tgggcattgc tggactgatg gttgCtttga gcccacagga=
GEM :1051=gctccctttt tgaattgtgt ggagaAgtgt gttctgatga ggcattttac=
GEM :1101=tatgcctgtt gatctatggg aaatctaggc gaaagtaatg gggaagatta=
GEM :1151=gaaagaAtta gccaaccagg ctacagttga tatttaaaag atccatttaa=
GEM :1201=aacaagctga tagtgtttcg ttaagcagta catcttgtGc atgcaaaaat=
GEM :1251=gaatTcaccc ctcccacctc tttcttcaat taatggaaaa CTgttaaggg=
GEM :1301=aagctgatac agagagacaa cttgctcctt tccatcagct ttatAATAAA=
GEM :1351=ctgtttaacg t=1361_ //note: ^^^^^^\
%-------
<** Segment_4:> [3'-unverified= 136 bp]
%-------
GEM :1362=?gaggtttca gtagctcctt ggttttgcct ctttaaatta tgacg?gcac=
ref3 :1448=_......... .......... .......... .......... .....T....=
ref4 :1267=T......... .......... .......... .......... ....._....=
GEM :????=aaaccttctt t?caatgcaa tgcatctgaa agtt?tgata cttgtaactt=
ref3 :1497=.......... .T........ .......... ....T..... ..........=
ref4 :1316=.......... ._........ .......... ...._..... ..........=
GEM :????=tttttttttt tt?ggttgca attgtttaag aatcatgg?=1497_
ref3 :1547=.......... .._....... .......... ........_=1583_
ref4 :1364=.......... ..T....... .......... ........G=1402_
%-------
<** Segment_5:> [3'-verified= 144 bp]
%-------
GEM :1498=atttattttt tgtaactctt tggctattgt ccttgtgtat cctgacagcg=
GEM :1548=ccatgtgtgt cagcccatgt caatcaagat gggtgattat gaaatgccag=
GEM :1598=acttctaa_AATAAAtgtttt ggaattcaat gggta_AATAAAtgc=1641_
//note: ^^^^^^ ^^^^^^\
<** Segment_6:> [3'-unverified_tail= 16? bp]
%-------
GEM :1642=??ctttgggg atatta=1657\
ref4 :1547=TG........ ......=1562\
ref3 :1728=GA.=1730\"

ECR

 "<* CROSS-REFERENCES_to:> [PRT_DB]
/ID: swp:Q04917^143F_HUMAN| prt= 199 aa /Date= Oct-01-1993^Feb-01-1994;
/Duplicated_by: cbi:416556\
/ID: pir:S34756^S29339 ...| prt= 199 aa /Date= Dec-31-1993^May-03-1994;
//note: incl S34753ref\
/ID: pir:S38509 ..........| prt= 246 aa /Date= Feb-18-1994;
/Duplicated_by: cbi:481360\
/ID: pir:S38532 ..........| prt= 246 aa /Date= Feb-18-1994;
/Duplicated_by: cbi:481365\
/ID: pir:S42476 ..........| prt= 246 aa /Date= Jan-06-1995^Apr-12-1995;
/Duplicated_by: cbi:542740\
/ID: prosite:PS00796-797\
<* CROSS-REFERENCES_to:> [DNA_DB]
/ID: emb:X57345^HSAS1MRNA.| cDNA= 601 bp /Date= Jan-23-1991^Jul-19-1993\
/ID: gnb:T11377...........| cDNA= 62 bp /Date= Nov-29-1993;
^EST /Duplicated_by: cbi:391531\
/ID: gnb:L20422^HUM1433ACT| cDNA= 1562 bp /Date= Feb-25-1994;
/Duplicated_by: cbi:437362-363\
/ID: emb:X78138^HSETARNA..| cDNA= 1398 bp /Date= Mar-14-1994;
/Duplicated_by: cbi:460778-779\
/ID: emb:X80536^HS1433PR..| cDNA= 1730 bp /Date= Aug-18-1994;
/Duplicated_by: cbi:531589-590\
/ID: emb:F08031^HSC2OD081.| cDNA= 308 bp /Date= Feb-17-1995;
^EST /Duplicated_by: cbi:677535\"

REF

 IDN,PRT,CLO,MAM "Ichimura T &: PNAS, 85, N19 (Oct), 7084-7088, 1988
CLO,SEQ,COD,LOC,MOL "Ichimura-Ohshima Y &: J Neurosci Res, 31, N4 (Apr), 600-605, 1992
CLO,SEQ,COD,EXP "Leffers H &: J Mol Biol, 231, N4 (Jun 20), 982-998, 1993
CLO,SEQ,COD,EXP "Swanson KD &: BBA, 1216, N1 (Oct 19), 145-148, 1993
EXP "Takeda J &: Hum Mol Genet, 2, N11 (Nov), 1793-1798, 1993
LOC "Tommerup N, Leffers H: Genomics, 33, 149-150, 1996

KEY

 neu, aac, sign

CLA

 coding, basic

LOC

 22 q12

MIM

 MIM: 113508

SYN

 YWHA1 AS1

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