Gene: [02p25/YWHAZ] tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, delta polypeptide (phosphorylated); brain protein 14-3-3, zeta subtype (phosphorylated delta subtype included); phospholipase A2-like? (brain protein 14-3-3 zeta);

COM

[1] Previously considered a distinctive member of the 14-3-3 family, the delta isoform is now included in the zeta subtype as the post-transla- tionally phosphorylated product of the latter (Aitken-1995).
[2] Basic information about this protein and its mRNA in man is presented in Zupan LA &:1992. Additional data relevant to functions of the protein can be found in Isobe T &:1992 and Fu H &:1993, although bovine 14-3-3 proteins were mostly discussed in these two publications.
[3] It remains yet unclear which particular type of phospholipase A2 ac- tivities is associated with this gene product. There are at least the two other genes which are directly correlated with the mentioned enzyma- tic function (GEM:12q2/PLA2G1B; GEM:01p35/PLA2G2A). On the other hand, in a recent publication by Robinson K &:1994, the authors did not find PLA2 activity in brain 14-3-3 proteins tested including zeta isoform on which the original observation was made.
[4] The SwissProt entry_record P29312, directly relevant to human 14-3-3 zeta, contains some confusing comments and references which will be dis- cussed in the sections 'Summary' and 'Coding_region'.
[5] For general information about this protein family, see 'Summary' in FAM:BP1433/00.0"

SUM

<*> [ZUPAN LA &:1992] (Dept of Medicine, Washington Univ School of Med- icine, St.Louis, Missouri 63110), refer to their previus study (Loeb LA, Gross RW: JBC, 261, 10467-470, 1986) in which they reported that the major phospholipase A2 activity (in sheep platelets) is mediated by at least three isoforms of a 30-kDa dimeric polypeptide which are respon- sive to physiologic increments in calcium ion and possess a significant substrate selectivity. Based on these data, they cloned the human homo- logue of one such isoform and showed that it catalyzes the cleavage of the sn-2 fatty acid of choline and ethanolamine glycerophospholipids through the formation of a stable acyl-enzyme intermediate. They also showed that 'transesterification of the sn-2 acyl group of phosphatidyl- choline to the recombinant 30-kDa polypeptide is over 50-fold selective for arachidonic acid, is augmented by calcium ion, and results in the formation of an arachidonoyl-thioester intermediate'. Sequence analysis showed that the polypeptide mediating this transesterification is a mem- ber of the 14-3-3 protein family. Finally, the authors conclude that 'their results demonstrate that at least one intracellular mammalian phospholipase A2 employs a catalytic strategy distinct from that util- ized by extracellular phospholipases A2 (ie, formation of an acyl-enzyme intermediate by nucleophilic attack versus activation of a water mole- cule) and that arachidonic acid in endogenous phospholipid storage de- pots can be sequentially transferred through an acyl-enzyme intermediate without the prior obligatory release of free arachidonic acid'. %----------------------------------------------------------------------- <*> [ISOBE T &:1992] (Dept of Chemistry, Facul of Science, Tokyo Metro- politan Univ, Japan), in their publication entitled 'Activation of pro- tein kinase C by the 14-3-3 proteins homologous with Exo1 protein that stimulates calcium-dependent exocytosis', reported that '..it has been demonstrated that a member of the 14-3-3 family, termed Exo1, stimulates Ca(2+)-dependent exocytosis in permeabilized adrenal chromaffin cells, suggesting that this protein family may influence the protein kinase C -mediated control of Ca(2+)-dependent exocytosis'. Based on these data, the authors showed that the 14-3-3 proteins activate protein kinase C at 2-fold more than the known level of the activated protein kinase C in the presence of Ca2+ and phospholipids. They suggested the possibility 'that the cellular activity of protein kinase C is regulated by diverse members of the 14-3-3 family' and that the ability of Exo1 to reactivate Ca(2+)-dependent exocytosis 'is based on its stimulatory effect on pro- tein kinase C activity.' Thus, the 14-3-3 family can be considered 'a multifunctional regulator of cell signalling processes mediated by two types of Ca(2+)-dependent protein kinase, protein kinase C and type II calmodulin-dependent protein kinase.' /Note: The above text was probably used in updating comments included in the SwissProt entry_record P29312 directly relevant to the human 14-3-3 zeta protein: (the protein) '.. STRONGLY ACTIVATES protein kinase C ..'. However, this remark is evidently inconsistent with the definition (of the protein) presented in the title of the same entry_record (see 'Sources' in 'Coding_region')\ %----------------------------------------------------------------------- <*> [FU H &:1993] (Dept Microbiology & Mol Genetics, Harvard Med School, Boston, MA 02115) discovered that the eukaryotic host factor activating exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. The authors referred to the following facts: Exoenzyme S, ExoS, that has been implicated as a virulence factor of P.aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins; its preferred substrates include Ras and several other 21- to 25-kDa GTP-binding proteins; ExoS absolutely requires a ubiquitous eu- karyotic protein factor, termed FAS (Factor Activating exoS), for enzy- matic activity. The authors described the cloning and expression of a gene encoding FAS from a bovine brain cDNA library and showed that pur- ified recombinant FAS produced in Escherichia coli activates ExoS in a defined cell-free system. The putative amino acid sequence of FAS shows that the protein (245 aa residues; MW 27,743 Da) belongs to a highly conserved, widely distributed eukaryotic protein family, designated as 14-3-3 proteins. Various functions have been reported for members of this family, including phospholipase A2 activity and regulation of tyro- sine/tryptophan hydroxylases and protein kinase C activities. Discovering of FAS as a 14-3-3 protein establishes an additional function for this protein family - the activation of an exogenous ADP-ribosyltransferase. %----------------------------------------------------------------------- <*> [THE CRYSTAL STRUCTURES] of bovine 14-3-3 zeta and human tau homodi- mers were recently published by Dong Liu &:1995 (Dana-Farber Cancer Inst and Dept Biol Chemistry and Mol Pharmacology, Harvard Medical School, 44 Binney Str, Boston, MA 02115, USA) and Bing Xiao &:1995 (Div of Protein Structure, National Inst for Medical Res, The Ridgeway, Mill Hill,London NW7 1AA, UK), respectively. For details of the results, see 'Summary' in FAM:BP1433/00.0"

COD

"<* ="<*" sources="BR" title="{PRT="><** during="J" and="phospholysis:" biol="<***" la="/ID:" cited="[GENBank] /ID: gnb:M86400^HUMPHPLA2| cDNA= 2834 bp;
'Human phospholipase A2 mRNA, complete cds';
//note: from a placental cDNA library\
/Date: Jul-20-1992\
/Duplicated_by: cbi:189952-953\
%-----------------------------------------------------------------------
<*** record="[SwissPROT] /ID: swp:P29312^143Z_HUMAN^P29213| prt= 245 aa (MW= ?);
'14-3-3 protein zeta - protein kinase C inhibitor protein-1
(KCIP-1) and phospholipase A2 and factor activating exo-
enzyme S (FAS)'\
/Date: Dec-01-1992^Oct-01-1994\
/Duplicated_by: cbi:112695\
/Note_1: This swp:entry contains incorrect references to two publica-
tions (Isobe T &:1992 and Fu H &:1993) and three entries (gnb:L07955,
pir:S15076, and pir:S34754^S29342), none of which are related to the
HUMAN 14-3-3 ZETA protein since the sources describe indeed either
BOVINE zeta or the human TAU and THETA proteins, respectively. Hence,
the 'conflict in the position #25: C/Cys <-|-> A/Ala' mentioned in
the item 'Feature' in this swp:record (below) is irrelevant to the
human 14-3-3 zeta amino acid sequence\
/Note_2: There is also the following confusing remark: (the protein)
'..STRONGLY ACTIVATES protein kinase C', that is inconsistent with
the definition of the zeta protein, presented above. On the other
hand, this swp:entry refers to Isobe T &:1992, where the authors re-
ported that one of the 14-3-3 proteins homologous to ExoI activates
the protein kinase C (see 'Summary')\
/Features: total= 1..245 //note: 14-3-3 protein zeta;
site= 1 //note: acetylation (putative);
site= 58 //note: phosphorylation (putative);
site= 63 //note: phosphorylation (putative);
region= 172..245 //note: binding region to the regula-
tory domain of hydroxylases\
%-----------------------------------------------------------------------
<**** record="[PIR] /ID: pir:A38246^PSHUAM| prt= 245 aa (MW= 27745);
'phospholipase A2 (acyl-enzyme intermediate-forming;
EC:3.1.1.- ), human'\
/Date: Dec-31-1992^Jun-30-1993\
/Note: This pir:record contains the following useful commentary - 'In
known examples of extracellular phospholipase A2, activation of a
water molecule for cleavage of ester linkages leads to the obliga-
tory release of free fatty acids. In contrast, this intracellular
phospholipase, a member of the family of 14-3-3 proteins, forms a
stable arachidonoyl-enzyme intermediate during catalysis. In prin-
ciple, this enzyme could transfer arachidonic acid sequentially to
acceptors other than water, without the release of free arachidonic
acid.'\
%-----------------------------------------------------------------------
<* features="BR"><** notes="BR"> /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: 'ref1' is Zupan LA &:1992\
/Note_3: The region (82..88:gtcATGg) is referred to as the 'Kozak
initiation sequence', in ref1 (gnb:M86400), although no evident
consensus with other 14-3-3 sequences is found except the 'atg'
start codon itself\
<** landmarks="BR"> {seg(1..84) = 5'-UTL(= 84);
seg(85..819) = CDS(= 735) //note: for 245 amino acids;
pos:85 = TLI_1 //note: <_atg> translation START;
seg(820..2834) = 3'-UTL(=2015);
pos:820 = TLT_1 //note: <_taa> translation STOP;
pos:1187 = TTS_1? //note: signal?;
pos:1800 = TTS_2? //note: signal?;
pos:2774 = TTS_3 //note: signal;
pos:? = TCT_1? //note: polyA-site?}
%-----------------------------------------------------------------------
<* ="%-------- ref1: 1=gcccactccc accgccagct ggaaccctgg ggactacgac gtccctcaaa=
ref1: 51=ccttgcttct aggagataaa aagaacatcc agtc=84_
%-------%
<** ="%-------- pep: 1= M D K N E L V Q K A K L A E Q =
ref1: 85=atg gat aaa aat gag ctg gtt cag aag gcc aaa ctg gcc gag cag=
pep: 16= A E R Y D D M A A C M K S V T =
ref1: 130=gct gag cga tat gat gac atg gca gcc tgc atg aag tct gta act=
pep: 31= E Q G A E L S N E E R N L L S =
ref1: 175=gag caa gga gct gaa tta tcc aat gag gag agg aat ctt ctc tca=
pep: 46= V A Y K N V V G A R R S S W R =
ref1: 220=gtt gct tat aaa aat gtt gta gga gcc cgt agg tca tct tgg agg=
pep: 61= V V S S I E Q K T E G A E K K =
ref1: 265=gtc gtc tca agt att gaa caa aag acg gaa ggt gct gag aaa aaa=
pep: 76= Q Q M A R E Y R E K I E T E L =
ref1: 310=cag cag atg gct cga gaa tac aga gag aaa att gag acg gag cta=
pep: 91= R D I C N D V L S L L E K F L =
ref1: 355=aga gat atc tgc aat gat gta ctg tct ctt ttg gaa aag ttc ttg=
pep: 106= I P N A S Q A E S K V F Y L K =
ref1: 400=atc ccc aat gct tca caa gca gag agc aaa gtc ttc tat ttg aaa=
pep: 121= M K G D Y Y R Y L A E V A A G =
ref1: 445=atg aaa gga gat tac tac cgt tac ttg gct gag gtt gcc gct ggt=
pep: 136= D D K K G I V D Q S Q Q A Y Q =
ref1: 490=gat gac aag aaa ggg att gtc gat cag tca caa caa gca tac caa=
pep: 151= E A F E I S K K E M Q P T H P =
ref1: 535=gaa gct ttt gaa atc agc aaa aag gaa atg caa cca aca cat cct=
pep: 166= I R L G L A L N F S V F Y Y E =
ref1: 580=atc aga ctg ggt ctg gcc ctt aac ttc tct gtg ttc tat tat gag=
pep: 181= I L N S P E K A C S L A K T A =
ref1: 625=att ctg aac tcc cca gag aaa gcc tgc tct ctt gca aag aca gct=
pep: 196= F D E A I A E L D T L S E E S =
ref1: 670=ttt gat gaa gcc att gct gaa ctt gat aca tta agt gaa gag tca=
pep 211= Y K D S T L I M Q L L R D N L =
ref1: 715=tac aaa gac agc acg cta ata atg caa tta ctg aga gac aac ttg=
pep 226= T L W T S D T Q G D E A E A G =
ref1: 760=aca ttg tgg aca tcg gat acc caa gga gac gaa gct gaa gca gga=
pep: 241= E G G E N =245\
ref1: 805=gaa gga ggg gaa aat=819_
%--------
<** ="%-------- ref1: 820=TAAccggcct tccaactttt gtctgcctca ttctaaaatt tacacagtag=
ref1: 870=accatttgtc atccatgctg tcccacaaat agttttttgt ttacgattta=
ref1: 920=tgacaggttt atgttacttc tatttgaatt tctatatttc ccatgtggtt=
ref1: 970=tttatgttta atattagggg agtagagcca gttaacattt agggagttat=
ref1:1020=ctgttttcat cttgaggtgg ccaatatggg gatgtggaat ttttatacaa=
ref1:1070=gttataagtg tttggcatag tacttttggt acattgtggc ttcaaaaggg=
ref1:1120=ccagtgtaaa actgcttcca tgtctaagca aagaaaactg cctacatact=
ref1:1170=ggtttgtcct ggcggggAAT AAAagggatc attggttcca gtcacaggtg=
ref1:1220=tagtaattgt gggtacttta aggtttggag cacttacaag gctgtggtag=
ref1:1270=aatcataccc catggatacc acatattaaa ccatgtatat ctgtggaata=
ref1:1320=ctcaatgtgt acacctttga ctacagctgc agaagtgttc ctttagacaa=
ref1:1370=agttgtgacc cattttactc tggataaggg cagaaacggt tcacattcca=
ref1:1420=ttatttgtaa agttacctgc tgttagcttt cattattttt gctacactca=
ref1:1470=ttttatttgt atttaaatgt tttaggcaac ctaagaacaa atgtaaaagt=
ref1:1520=aaagatgcag gaaaaatgaa ttgcttggta ttcattactt catgtatatc=
ref1:1570=aagcacagca gtaaaacaaa aacccatgta tttaactttt ttttaggatt=
ref1:1620=tttgcttttg tgattttttt tttttttttt tgatacttgc ctaacatgca=
ref1:1670=tgtgctgtaa aaatagttaa cagggaaata acttgagatg atggctagct=
ref1:1720=ttgtttaatg tcttatgaaa ttttcatgaa caatccaagc ataattgtta=
ref1:1770=agaacacgtg tattaaattc atgtaagtgg AATAAAagtt ttatgaatgg=
ref1:1820=acttttcaac tactttctct acagcttttc atgtaaatta gtcttggttc=
ref1:1870=tgaaacttct ctaaaggaaa ttgtacattc tttgaaattt attccttatt=
ref1:1920=ccctcttggc agctaatggg ctcttaccaa gtttaaacac aaaatttatc=
ref1:1970=ataacaaaaa tactactaat ataactactg tttccatgtc ccatgatccc=
ref1:2020=ctctcttcct ccccaccctg aaaaaaatga gttcctattt tttctgggag=
ref1:2070=agggggggat tgattagaaa aaaatgtagt gtgttccatt taaaattttg=
ref1:2120=gcatatggca ttttctaact taggaagcca caatgttctt ggcccatcat=
ref1:2170=gacattgggt agcattaact gtaagttttg tgcttccaaa tcactttttg=
ref1:2220=gtttttaaga atttcttgat actcttatag cctgccttca attttgatcc=
ref1:2270=tttattcttt ctatttgtca ggtgcacaag attaccttcc tgttttagcc=
ref1:2320=ttctgtcttg tcaccaacca ttcttacttg gtggccatgt acttggaaaa=
ref1:2370=aggccgcatg atctttctgg ctccactcag tgtctaaggc accctgcttc=
ref1:2420=ctttgcttgc atcccacaga ctatttccct catcctattt actgcagcaa=
ref1:2470=atctctcctt agttgatgag actgtgttta tctcccttta aaaccctacc=
ref1:2520=tatcctgaat ggtctgtcat tgtctgcctt taaaatcctt cctctttctt=
ref1:2570=cctcctctat tctctaaata atgatggggc taagttatac ccaaagctca=
ref1:2620=ctttacaaaa tatttcctca gtactttgca gaaaacacca aacaaaaatg=
ref1:2670=ccattttaaa aaaggtgtat tttttctttt agaatgtaag ctcctcaaga=
ref1:2720=gcagggacaa tgttttctgt atgttctatt gtgcctagta cactgtaaat=
ref1:2770=gctcAATAAA tattgatgat gggaggcagt gagtcttgat gataagggtg=
ref1:2820=agaaactgaa atccc=2834\"

ECR

"<* cross-references="[PROT_DB] /ID: swp:P29312^143Z_HUMAN^P29213| prt= 245 aa /Date: Dec-01-1992^Oct-01-1994;
/Duplicated_by: cbi:112695\
/ID: pir:A38246^PSHUAM...........| prt= 245 aa /Date: Dec-31-1992^Jun-30-1993\
/ID: prosite:PS00796-797\
<* cross-references="[DNA_DB] /ID: gnb:M86400^HUMPHPLA2| cDNA= 2834 bp /Date: Jul-20-1992;
/Duplicated_by: cbi:189952-953\"

REF

PRT,PTM,SYS "Aitken A &: JBC, 270, N11 (Mar 17), 5706-5709, 1995
FUN,EXP,EVO,MAM "Fu H &: PNAS, 90, N6 (Mar 15), 2320-2324, 1993
FUN,EXP,EVO,MAM "Isobe T &: FEBS Lett, 308, N2 (Aug 17), 121-124, 1992
MOP,STR,MOL "Liu D &: Nature, 376, N6536 (Jul 13), 191-194, 1995
COM,FUN "Robinson K &: Biochem J, 299 (Pt 3), N0 (May 1), 853-861, 1994
LOC "Tommerup N, Leffers H: Genomics, 33, 149-150, 1996
MOP,STR,MOL "Xiao B &: Nature, 376, N6536 (Jul 13), 188-191, 1995
CLO,SEQ,COD,LOC,MOL "Zupan LA &: JBC, 267, N13 (May 5), 8707-8710, 1992

SWI

SWISSPROT: P29312

KEY

aac, sign, lip, horm

CLA

coding, basic

LOC

02 p25.2-.1

MIM

MIM: 601288

EZN

ENZYME: 3.1.1.?

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