ID   1433Z_BOVIN             Reviewed;         245 AA.
AC   P63103; P29213; P29312; Q3ZCF9;
DT   13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-SEP-2004, sequence version 1.
DT   02-SEP-2026, entry version 174.
DE   RecName: Full=14-3-3 protein zeta/delta;
DE   AltName: Full=Factor activating exoenzyme S;
DE            Short=FAS;
DE   AltName: Full=Protein kinase C inhibitor protein 1;
DE            Short=KCIP-1;
GN   Name=YWHAZ;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   PROTEIN SEQUENCE.
RC   TISSUE=Brain;
RX   PubMed=1499718; DOI=10.1016/0014-5793(92)81257-m;
RA   Isobe T., Hiyane Y., Ichimura T., Okuyama T., Takahashi N., Nakajo S.,
RA   Nakaya K.;
RT   "Activation of protein kinase C by the 14-3-3 proteins homologous with Exo1
RT   protein that stimulates calcium-dependent exocytosis.";
RL   FEBS Lett. 308:121-124(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 104-115; 140-157 AND
RP   194-212.
RC   TISSUE=Brain;
RX   PubMed=8460141; DOI=10.1073/pnas.90.6.2320;
RA   Fu H., Coburn J., Collier R.J.;
RT   "The eukaryotic host factor that activates exoenzyme S of Pseudomonas
RT   aeruginosa is a member of the 14-3-3 protein family.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:2320-2324(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION.
RX   PubMed=7931346; DOI=10.1046/j.1471-4159.1994.63051908.x;
RA   Tanji M., Horwitz R., Rosenfeld G., Waymire J.C.;
RT   "Activation of protein kinase C by purified bovine brain 14-3-3: comparison
RT   with tyrosine hydroxylase activation.";
RL   J. Neurochem. 63:1908-1916(1994).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=7603574; DOI=10.1038/376191a0;
RA   Liu D., Blenkowska J., Petosa C., Collier R.J., Fu H., Liddington R.;
RT   "Crystal structure of the zeta isoform of the 14-3-3 protein.";
RL   Nature 376:191-194(1995).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) IN COMPLEX WITH PHOSPHORYLATED RAF1,
RP   INTERACTION WITH PHOSPHOSERINE PEPTIDE, AND SUBUNIT.
RX   PubMed=9632691; DOI=10.1074/jbc.273.26.16305;
RA   Petosa C., Masters S.C., Bankston L.A., Pohl J., Wang B., Fu H.,
RA   Liddington R.C.;
RT   "14-3-3zeta binds a phosphorylated Raf peptide and an unphosphorylated
RT   peptide via its conserved amphipathic groove.";
RL   J. Biol. Chem. 273:16305-16310(1998).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PHOSPHORYLATED ITGB2,
RP   AND INTERACTION WITH PHOSPHORYLATED ITGB2.
RX   PubMed=18550856; DOI=10.1182/blood-2007-12-127795;
RA   Takala H., Nurminen E., Nurmi S.M., Aatonen M., Strandin T., Takatalo M.,
RA   Kiema T., Gahmberg C.G., Ylaenne J., Fagerholm S.C.;
RT   "Beta2 integrin phosphorylation on Thr758 acts as a molecular switch to
RT   regulate 14-3-3 and filamin binding.";
RL   Blood 112:1853-1862(2008).
CC   -!- FUNCTION: Adapter protein implicated in the regulation of a large
CC       spectrum of both general and specialized signaling pathways
CC       (PubMed:7931346). Binds to a large number of partners, usually by
CC       recognition of a phosphoserine or phosphothreonine motif
CC       (PubMed:7931346). Binding generally results in the modulation of the
CC       activity of the binding partner (PubMed:7931346). Promotes cytosolic
CC       retention and inactivation of TFEB transcription factor by binding to
CC       phosphorylated TFEB. Induces ARHGEF7 activity on RAC1 as well as
CC       lamellipodia and membrane ruffle formation (By similarity). In neurons,
CC       regulates spine maturation through the modulation of ARHGEF7 activity
CC       (By similarity). {ECO:0000250|UniProtKB:O55043,
CC       ECO:0000250|UniProtKB:P63104, ECO:0000269|PubMed:7931346}.
CC   -!- SUBUNIT: Homodimer. Heterodimerizes with YWHAE (By similarity).
CC       Homo- and heterodimerization is inhibited by phosphorylation on Ser-58
CC       (By similarity). Interacts with FOXO4, NOXA1, SSH1 ARHGEF2, CDK16 and
CC       BSPRY. Interacts with WEE1 (C-terminal). Interacts with MLF1
CC       (phosphorylated form); the interaction retains it in the cytoplasm.
CC       Interacts with BAX; the interaction occurs in the cytoplasm. Under
CC       stress conditions, MAPK8-mediated phosphorylation releases BAX to
CC       mitochondria. Interacts with TP53; the interaction enhances p53
CC       transcriptional activity. The Ser-58 phosphorylated form inhibits this
CC       interaction and p53 transcriptional activity. Interacts with ABL1
CC       (phosphorylated form); the interaction retains ABL1 in the cytoplasm.
CC       Interacts with PKA-phosphorylated AANAT; the interaction modulates
CC       AANAT 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 (By similarity). Interacts with AKT1; the interaction
CC       phosphorylates YWHAZ and modulates dimerization (By similarity).
CC       Interacts with GAB2. Interacts with BCL2L11, SAMSN1 and TLK2 (By
CC       similarity). Interacts with phosphorylated RAF1; the interaction is
CC       inhibited when YWHAZ is phosphorylated on Thr-232. Interacts with Thr-
CC       phosphorylated ITGB2. Interacts with the 'Thr-369' phosphorylated form
CC       of DAPK2 (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B
CC       (By similarity). Interacts with ZFP36L1 (via phosphorylated form); this
CC       interaction occurs in a p38 MAPK- and AKT-signaling pathways (By
CC       similarity). Interacts with SLITRK1 (By similarity). Interacts with
CC       AK5, LDB1, MADD, MARK3, PDE1A and SMARCB1 (By similarity). Interacts
CC       with YWHAZ (By similarity). Interacts with MEFV (By similarity).
CC       Interacts with ADAM22 (via C-terminus) (By similarity).
CC       {ECO:0000250|UniProtKB:P63101, ECO:0000250|UniProtKB:P63104,
CC       ECO:0000250|UniProtKB:Q9ES28, ECO:0000269|PubMed:18550856,
CC       ECO:0000269|PubMed:9632691}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63104}.
CC       Melanosome {ECO:0000250|UniProtKB:P63104}. Note=Located to stage I to
CC       stage IV melanosomes. {ECO:0000250|UniProtKB:P63104}.
CC   -!- PTM: The delta, brain-specific form differs from the zeta form in being
CC       phosphorylated. Phosphorylation on Ser-184 by MAPK8; promotes
CC       dissociation of BAX and translocation of BAX to mitochondria.
CC       Phosphorylation on Thr-232; inhibits binding of RAF1. Phosphorylated on
CC       Ser-58 by PKA and protein kinase C delta type catalytic subunit in a
CC       sphingosine-dependent fashion. Phosphorylation on Ser-58 by PKA;
CC       disrupts homodimerization and heterodimerization with YHAE and TP53.
CC       {ECO:0000250|UniProtKB:P63104}.
CC   -!- SIMILARITY: Belongs to the 14-3-3 family. {ECO:0000305}.
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DR   EMBL; L07955; AAA30514.1; -; mRNA.
DR   EMBL; BC102382; AAI02383.1; -; mRNA.
DR   PIR; A47389; A47389.
DR   PIR; S65013; S65013.
DR   RefSeq; NP_777239.1; NM_174814.2.
DR   RefSeq; XP_024857197.1; XM_025001429.2.
DR   RefSeq; XP_024857198.1; XM_025001430.2.
DR   PDB; 1A37; X-ray; 3.60 A; A/B=1-245.
DR   PDB; 1A38; X-ray; 3.35 A; A/B=1-245.
DR   PDB; 1A4O; X-ray; 2.80 A; A/B/C/D=1-245.
DR   PDB; 2V7D; X-ray; 2.50 A; A/B/C/D=1-245.
DR   AlphaFoldDB; P63103; -.
DR   BMRB; P63103; -.
DR   SMR; P63103; -.
DR   BioGRID; 160005; 5.
DR   CORUM; P63103; -.
DR   FunCoup; P63103; 3185.
DR   IntAct; P63103; 10.
DR   MINT; P63103; -.
DR   STRING; 9913.ENSBTAP00000000289; -.
DR   PaxDb; 9913-ENSBTAP00000000289; -.
DR   PeptideAtlas; P63103; -.
DR   Ensembl; ENSBTAT00000000289.7; ENSBTAP00000000289.4; ENSBTAG00000000236.7.
DR   Ensembl; ENSBTAT00085045106; ENSBTAP00085028139; ENSBTAG00085000367.
DR   Ensembl; ENSBTAT00090037085; ENSBTAP00090018937; ENSBTAG00090018372.
DR   GeneID; 287022; -.
DR   KEGG; bta:287022; -.
DR   CTD; 7534; -.
DR   VEuPathDB; HostDB:ENSBTAG00000000236; -.
DR   VGNC; VGNC:53885; YWHAZ.
DR   eggNOG; KOG0841; Eukaryota.
DR   GeneTree; ENSGT01090000260040; -.
DR   HOGENOM; CLU_058290_1_0_1; -.
DR   InParanoid; P63103; -.
DR   OMA; YDEMVNE; -.
DR   OrthoDB; 10260625at2759; -.
DR   Reactome; R-BTA-111447; Activation of BAD and translocation to mitochondria.
DR   Reactome; R-BTA-3769402; Deactivation of the beta-catenin transactivating complex.
DR   Reactome; R-BTA-392517; Rap1 signalling.
DR   Reactome; R-BTA-430116; GP1b-IX-V activation signalling.
DR   Reactome; R-BTA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR   Reactome; R-BTA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR   Reactome; R-BTA-5625740; RHO GTPases activate PKNs.
DR   Reactome; R-BTA-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-BTA-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR   Reactome; R-BTA-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus.
DR   Reactome; R-BTA-9614399; Regulation of localization of FOXO transcription factors.
DR   EvolutionaryTrace; P63103; -.
DR   PRO; PR:P63103; -.
DR   Proteomes; UP000009136; Chromosome 14.
DR   Bgee; ENSBTAG00000000236; Expressed in occipital lobe and 108 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR   GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0050815; F:phosphoserine residue binding; ISS:UniProtKB.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR   GO; GO:0140311; F:protein sequestering activity; ISS:UniProtKB.
DR   GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR   GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR   GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR   GO; GO:0051683; P:establishment of Golgi localization; IEA:Ensembl.
DR   GO; GO:0090168; P:Golgi reassembly; IEA:Ensembl.
DR   GO; GO:0008104; P:intracellular protein localization; IBA:GO_Central.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0045824; P:negative regulation of innate immune response; IEA:Ensembl.
DR   GO; GO:1900181; P:negative regulation of protein localization to nucleus; IEA:Ensembl.
DR   GO; GO:1904262; P:negative regulation of TORC1 signaling; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0090128; P:regulation of synapse maturation; IEA:Ensembl.
DR   GO; GO:0003016; P:respiratory system process; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; ISS:UniProtKB.
DR   GO; GO:0008039; P:synaptic target recognition; IEA:Ensembl.
DR   GO; GO:0035148; P:tube formation; IEA:Ensembl.
DR   CDD; cd10022; 14-3-3_beta_zeta; 1.
DR   DisProt; DP04073; -.
DR   FunFam; 1.20.190.20:FF:000001; 14-3-3 gamma 1; 1.
DR   Gene3D; 1.20.190.20; 14-3-3 domain; 1.
DR   InterPro; IPR000308; 14-3-3.
DR   InterPro; IPR023409; 14-3-3_CS.
DR   InterPro; IPR036815; 14-3-3_dom_sf.
DR   InterPro; IPR023410; 14-3-3_domain.
DR   PANTHER; PTHR18860; 14-3-3 PROTEIN; 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; 14-3-3 protein; 1.
DR   PROSITE; PS00796; 1433_1; 1.
DR   PROSITE; PS00797; 1433_2; 1.
DR   PDBsum; 1A37; -.
DR   PDBsum; 1A38; -.
DR   PDBsum; 1A4O; -.
DR   PDBsum; 2V7D; -.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..245
FT                   /note="14-3-3 protein zeta/delta"
FT                   /id="PRO_0000058626"
FT   SITE            56
FT                   /note="Interaction with phosphoserine on interacting
FT                   protein"
FT                   /evidence="ECO:0000269|PubMed:18550856,
FT                   ECO:0000269|PubMed:9632691"
FT   SITE            127
FT                   /note="Interaction with phosphoserine on interacting
FT                   protein"
FT                   /evidence="ECO:0000269|PubMed:18550856,
FT                   ECO:0000269|PubMed:9632691"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         3
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         58
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         68
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         184
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         207
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   MOD_RES         210
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P63102"
FT   MOD_RES         232
FT                   /note="Phosphothreonine; by CK1"
FT                   /evidence="ECO:0000250|UniProtKB:P63104"
FT   CONFLICT        25
FT                   /note="C -> A (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           3..15
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           19..30
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   TURN            31..33
FT                   /evidence="ECO:0007829|PDB:1A38"
FT   HELIX           35..37
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           38..67
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           74..99
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           100..105
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           106..108
FT                   /evidence="ECO:0007829|PDB:1A38"
FT   HELIX           112..115
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           117..131
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           137..156
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   TURN            157..159
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           165..176
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           177..181
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           185..201
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   TURN            202..205
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   TURN            208..210
FT                   /evidence="ECO:0007829|PDB:2V7D"
FT   HELIX           211..226
FT                   /evidence="ECO:0007829|PDB:2V7D"
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
//