Human Gene YWHAZ (uc011lhe.1) Description and Page Index
  Description: Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ), transcript variant 6, mRNA.
RefSeq Summary (NM_001135702): This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008].
Transcript (Including UTRs)
   Position: hg19 chr8:101,930,804-101,962,799 Size: 31,996 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr8:101,932,921-101,961,117 Size: 28,197 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr8:101,930,804-101,962,799)mRNA (may differ from genome)Protein (245 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
ReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: 1433Z_HUMAN
DESCRIPTION: RecName: Full=14-3-3 protein zeta/delta; AltName: Full=Protein kinase C inhibitor protein 1; Short=KCIP-1;
FUNCTION: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.
SUBUNIT: Interacts with CDK16 and BSPRY (By similarity). Interacts with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with Thr- phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By similarity). Homodimer. Heterodimerizes with YWHAE. Homo- and hetero-dimerization is inhibited by phosphorylation on Ser-58. Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2.
INTERACTION: Q29495:AANAT (xeno); NbExp=3; IntAct=EBI-347088, EBI-446413; P00519:ABL1; NbExp=2; IntAct=EBI-347088, EBI-375543; Q9P0K1-3:ADAM22; NbExp=3; IntAct=EBI-347088, EBI-1567267; O00257-3:CBX4; NbExp=2; IntAct=EBI-347088, EBI-4392727; P23528:CFL1; NbExp=2; IntAct=EBI-347088, EBI-352733; P00533:EGFR; NbExp=4; IntAct=EBI-347088, EBI-297353; P30793:GCH1; NbExp=4; IntAct=EBI-347088, EBI-958183; Q99683:MAP3K5; NbExp=2; IntAct=EBI-347088, EBI-476263; Q7KZI7:MARK2; NbExp=3; IntAct=EBI-347088, EBI-516560; P27448:MARK3; NbExp=6; IntAct=EBI-347088, EBI-707595; Q9NYL2:MLTK; NbExp=4; IntAct=EBI-347088, EBI-602273; Q8TEW0:PARD3; NbExp=3; IntAct=EBI-347088, EBI-81968; P04049:RAF1; NbExp=3; IntAct=EBI-347088, EBI-365996; P57059:SIK1; NbExp=4; IntAct=EBI-347088, EBI-1181640; Q9Y2K2:SIK3; NbExp=5; IntAct=EBI-347088, EBI-1181460; O00506:STK25; NbExp=2; IntAct=EBI-347088, EBI-618295; P36897:TGFBR1; NbExp=4; IntAct=EBI-347088, EBI-1027557; P84198:VIM (xeno); NbExp=5; IntAct=EBI-347088, EBI-457639;
SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Located to stage I to stage IV melanosomes.
PTM: The delta, brain-specific form differs from the zeta form in being phosphorylated (By similarity). Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria. Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53. This phosphorylation appears to be activated by sphingosine. Phosphorylation on Thr-232; inhibits binding of RAF1.
SIMILARITY: Belongs to the 14-3-3 family.
CAUTION: Was originally (PubMed:1577711) thought to have phospholipase A2 activity.
SEQUENCE CAUTION: Sequence=AAH51814.1; Type=Erroneous initiation; Sequence=AAH73141.1; Type=Erroneous initiation;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): YWHAZ
CDC HuGE Published Literature: YWHAZ
Positive Disease Associations: Amyotrophic Lateral Sclerosis , Attention deficit hyperactivity disorder and conduct disorder , Echocardiography , Lipoproteins, HDL
Related Studies:
  1. Amyotrophic Lateral Sclerosis
    Simon Cronin et al. Human molecular genetics 2008, A genome-wide association study of sporadic ALS in a homogenous Irish population., Human molecular genetics. [PubMed 18057069]
  2. Attention deficit hyperactivity disorder and conduct disorder
    Anney ,et al. 2008, Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study, American journal of medical genetics. Part B, Neuropsychiatric genetics 2008 147B- 8 : 1369-78. [PubMed 18951430]
  3. Echocardiography
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
           more ... click here to view the complete list

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C086401 pentabromodiphenyl ether
  • C059514 resveratrol
  • C029790 2,2',3',4,4',5-hexachlorobiphenyl
  • C016403 2,4-dinitrotoluene
  • C049584 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • C030370 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone
  • C472791 3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
  • C009505 4,4'-diaminodiphenylmethane
  • C477187 5-(4-methylpiperazin-1-yl)-2-(2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl)benzimidazole
  • D015127 9,10-Dimethyl-1,2-benzanthracene
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 166.87 RPKM in Esophagus - Mucosa
Total median expression: 3559.56 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -63.70177-0.360 Picture PostScript Text
3' UTR -522.052117-0.247 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000308 - 14-3-3
IPR023409 - 14-3-3_CS
IPR023410 - 14-3-3_domain

Pfam Domains:
PF00244 - 14-3-3 protein

SCOP Domains:
48445 - 14-3-3 protein

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray

- X-ray
To conserve bandwidth, only the images from the first 3 structures are shown.
2C1J - X-ray MuPIT 2C1N - X-ray MuPIT 2O02 - X-ray MuPIT
2WH0 - X-ray MuPIT 3CU8 - X-ray MuPIT 3NKX - X-ray MuPIT
3RDH - X-ray MuPIT 4FJ3 - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P63104
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding
GO:0031625 ubiquitin protein ligase binding
GO:0042802 identical protein binding
GO:0044325 ion channel binding
GO:0045296 cadherin binding

Biological Process:
GO:0007165 signal transduction
GO:0019221 cytokine-mediated signaling pathway
GO:0030168 platelet activation
GO:0043066 negative regulation of apoptotic process
GO:0043488 regulation of mRNA stability
GO:0051683 establishment of Golgi localization
GO:0061024 membrane organization
GO:0090168 Golgi reassembly
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Cellular Component:
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005925 focal adhesion
GO:0031982 vesicle
GO:0042470 melanosome
GO:0070062 extracellular exosome
GO:0072562 blood microparticle

-  Descriptions from all associated GenBank mRNAs
  EU794582 - Homo sapiens epididymis secretory protein Li 3 (HEL-S-3) mRNA, complete cds.
BC051814 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone IMAGE:5527579), partial cds.
BC072426 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:87788 IMAGE:6315583), complete cds.
EU794583 - Homo sapiens epididymis luminal protein 4 (HEL4) mRNA, complete cds.
GQ472215 - Homo sapiens epididymis secretory protein Li 93 (HEL-S-93) mRNA, complete cds.
M86400 - Human phospholipase A2 mRNA, complete cds.
JD449267 - Sequence 430291 from Patent EP1572962.
BC063824 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:74590 IMAGE:6180974), complete cds.
JD279968 - Sequence 260992 from Patent EP1572962.
BC073141 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone IMAGE:6504109), partial cds.
BC013265 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone IMAGE:3873977).
BC083508 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:87787 IMAGE:5563061), complete cds.
BC108281 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:111427 IMAGE:3869494), complete cds.
BC070389 - Homo sapiens cDNA clone IMAGE:4047193, partial cds.
BC068456 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:87045 IMAGE:4793291), complete cds.
JD423025 - Sequence 404049 from Patent EP1572962.
JD261102 - Sequence 242126 from Patent EP1572962.
JD419876 - Sequence 400900 from Patent EP1572962.
JD133779 - Sequence 114803 from Patent EP1572962.
JD563855 - Sequence 544879 from Patent EP1572962.
JD061316 - Sequence 42340 from Patent EP1572962.
JD059787 - Sequence 40811 from Patent EP1572962.
JD039019 - Sequence 20043 from Patent EP1572962.
JD279048 - Sequence 260072 from Patent EP1572962.
JD256285 - Sequence 237309 from Patent EP1572962.
JD567001 - Sequence 548025 from Patent EP1572962.
JD457764 - Sequence 438788 from Patent EP1572962.
JD050061 - Sequence 31085 from Patent EP1572962.
JD547121 - Sequence 528145 from Patent EP1572962.
JD258242 - Sequence 239266 from Patent EP1572962.
BC003623 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:2153 IMAGE:2988020), complete cds.
BC099904 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:104542 IMAGE:5298373), complete cds.
AK294647 - Homo sapiens cDNA FLJ50142 complete cds, highly similar to 14-3-3 protein zeta/delta (Protein kinase Cinhibitor protein 1).
AK296902 - Homo sapiens cDNA FLJ51775 complete cds, highly similar to 14-3-3 protein zeta/delta.
AK315867 - Homo sapiens cDNA, FLJ79516 complete cds, highly similar to 14-3-3 protein zeta/delta.
JC427580 - Sequence 12 from Patent EP2536436.
JD036789 - Sequence 17813 from Patent EP1572962.
JD504460 - Sequence 485484 from Patent EP1572962.
AK289945 - Homo sapiens cDNA FLJ76227 complete cds, highly similar to Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ), transcript variant 1, mRNA.
DQ185048 - Homo sapiens tyrosine 3-monooxygenasea/tryptophan 5-monooxygenase activation protein zeta mRNA, partial cds.
AK307506 - Homo sapiens cDNA, FLJ97454.
JD510653 - Sequence 491677 from Patent EP1572962.
U28964 - Homo sapiens 14-3-3 protein mRNA, complete cds.
JD314650 - Sequence 295674 from Patent EP1572962.
BC101483 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, mRNA (cDNA clone MGC:126532 IMAGE:8068989), complete cds.
BC111951 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, transcript variant 2, mRNA (cDNA clone MGC:138156 IMAGE:8327419), complete cds.
JD309708 - Sequence 290732 from Patent EP1572962.
DQ894884 - Synthetic construct Homo sapiens clone IMAGE:100009344; FLH184962.01L; RZPDo839D10145D tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ) gene, encodes complete protein.
DQ891706 - Synthetic construct clone IMAGE:100004336; FLH184966.01X; RZPDo839D10146D tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ) gene, encodes complete protein.
AB464332 - Synthetic construct DNA, clone: pF1KB5696, Homo sapiens YWHAZ gene for tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, without stop codon, in Flexi system.
JD073295 - Sequence 54319 from Patent EP1572962.
S79449 - 14-3-3 protein/cytosolic phospholipase A2 [human, lung adenocarcinoma cell line A549, mRNA Partial, 210 nt].

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04114 - Oocyte meiosis
hsa04722 - Neurotrophin signaling pathway
hsa05130 - Pathogenic Escherichia coli infection

Reactome (by CSHL, EBI, and GO)

Protein P63104 (Reactome details) participates in the following event(s):

R-HSA-912757 p-S585-IL3RB binds 14-3-3 proteins
R-HSA-3769393 YWHAZ binds p-CBY:CTNNB1
R-HSA-430076 GP1b-IX-V binds 14-3-3-zeta
R-HSA-443831 14-3-3-zeta binds Raf1
R-HSA-430073 GPIb-IX-V binding to 14-3-3 zeta is reduced by shear stress
R-HSA-914182 14-3-3 zeta binding allows recruitment of PI3K
R-HSA-913993 14-3-3 proteins beta and zeta bind and inhibit Rap1Gap2
R-HSA-3769391 XPO1 binds the beta-catenin:CBY complex
R-HSA-443402 GP1b-IX-V:13-3-3-zeta complexes with p85 PI3K
R-HSA-75016 Association of p-S216-CDC25C with 14-3-3 proteins
R-HSA-139899 Sequestration of BAD protein by 14-3-3
R-HSA-1445149 14-3-3 binds p-5S,T642-AS160 (TBC1D4)
R-HSA-1454689 14-3-3 Binds p-S237-TBC1D1
R-HSA-5632732 p-S939,T1462-TSC2 binding to 14-3-3 dimer is negatively regulated by DDIT4
R-HSA-5632738 DDIT4 binds 14-3-3 dimer
R-HSA-139906 Activation of BAD by calcineurin
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-430116 GP1b-IX-V activation signalling
R-HSA-392517 Rap1 signalling
R-HSA-449147 Signaling by Interleukins
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-111447 Activation of BAD and translocation to mitochondria
R-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-1280218 Adaptive Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-8953854 Metabolism of RNA
R-HSA-195721 Signaling by WNT
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-195258 RHO GTPase Effectors
R-HSA-114452 Activation of BH3-only proteins
R-HSA-199991 Membrane Trafficking
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-109582 Hemostasis
R-HSA-168256 Immune System
R-HSA-162582 Signal Transduction
R-HSA-69481 G2/M Checkpoints
R-HSA-194315 Signaling by Rho GTPases
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-5653656 Vesicle-mediated transport
R-HSA-212436 Generic Transcription Pathway
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-109581 Apoptosis
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-1640170 Cell Cycle
R-HSA-5357801 Programmed Cell Death
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: 1433Z_HUMAN, A8K1N0, NM_001135702, NP_663723, P29213, P29312, P63104, Q32P43, Q5XJ08, Q6GPI2, Q6IN74, Q6NUR9, Q6P3U9, Q86V33
UCSC ID: uc011lhe.1
RefSeq Accession: NM_001135702
Protein: P63104 (aka 1433Z_HUMAN or 143Z_HUMAN)
CCDS: CCDS6290.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001135702.1
exon count: 6CDS single in 3' UTR: no RNA size: 3042
ORF size: 738CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1574.00frame shift in genome: no % Coverage: 99.67
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.