Human Gene YWHAH (uc003alz.3) Description and Page Index
  Description: Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (YWHAH), mRNA.
RefSeq Summary (NM_003405): 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 bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1163658.310288.1, SRR3476690.534567.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000248975.6/ ENSP00000248975.5 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr22:32,340,479-32,353,590 Size: 13,112 Total Exon Count: 2 Strand: +
Coding Region
   Position: hg19 chr22:32,340,720-32,352,779 Size: 12,060 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr22:32,340,479-32,353,590)mRNA (may differ from genome)Protein (246 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
  ID: 1433F_HUMAN
DESCRIPTION: RecName: Full=14-3-3 protein eta; AltName: Full=Protein AS1;
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. Negatively regulates the kinase activity of PDPK1.
SUBUNIT: Homodimer (By similarity). Interacts with many nuclear hormone receptors and cofactors including AR, ESR1, ESR2, MC2R, NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with ARHGEF28 and CDK16 (By similarity). Weakly interacts with CDKN1B. Interacts with GAB2. Interacts with KCNK18 in a phosphorylation- dependent manner. Interacts with SAMSN1 (By similarity). Interacts with the 'Ser-241' phosphorylated form of PDPK1.
INTERACTION: O94921:CDK14; NbExp=3; IntAct=EBI-306940, EBI-1043945; O60565:GREM1; NbExp=5; IntAct=EBI-306940, EBI-944395; Q14678-2:KANK1; NbExp=3; IntAct=EBI-306940, EBI-6173812; Q7KZI7:MARK2; NbExp=6; IntAct=EBI-306940, EBI-516560; P27448:MARK3; NbExp=4; IntAct=EBI-306940, EBI-707595; Q96L34:MARK4; NbExp=6; IntAct=EBI-306940, EBI-302319; Q8TEW0:PARD3; NbExp=6; IntAct=EBI-306940, EBI-81968; Q9NPB6:PARD6A; NbExp=2; IntAct=EBI-306940, EBI-81876; Q9BYG5:PARD6B; NbExp=2; IntAct=EBI-306940, EBI-295391; Q9BYG4:PARD6G; NbExp=2; IntAct=EBI-306940, EBI-295417; P41743:PRKCI; NbExp=3; IntAct=EBI-306940, EBI-286199; P04049:RAF1; NbExp=2; IntAct=EBI-306940, EBI-365996;
TISSUE SPECIFICITY: Expressed mainly in the brain and present in other tissues albeit at lower levels.
SIMILARITY: Belongs to the 14-3-3 family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): YWHAH
CDC HuGE Published Literature: YWHAH
Positive Disease Associations: schizophrenia
Related Studies:
  1. schizophrenia
    Bell R 2000, Systematic screening of the 14-3-3 eta (eta) chain gene for polymorphic variants and case-control analysis in schizophrenia., American journal of medical genetics. 2000 Dec;96(6):736-43. [PubMed 11121172]
    Haplotype analysis of pairs of polymorphisms provided no evidence for association of this gene with schizophrenia in the population studied.
  2. schizophrenia
    Toyooka K 1999, , American journal of medical genetics. 1999 Apr;88(2):164-7. [PubMed 10206237]

-  MalaCards Disease Associations
  MalaCards Gene Search: YWHAH
Diseases sorted by gene-association score: schizophrenia (4), early-onset schizophrenia (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           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: 511.20 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 4694.67 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 -131.50241-0.546 Picture PostScript Text
3' UTR -208.32811-0.257 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 MuPIT

ModBase Predicted Comparative 3D Structure on Q04917
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:0003779 actin binding
GO:0005159 insulin-like growth factor receptor binding
GO:0005515 protein binding
GO:0017080 sodium channel regulator activity
GO:0019899 enzyme binding
GO:0019904 protein domain specific binding
GO:0035259 glucocorticoid receptor binding
GO:0042802 identical protein binding
GO:0044325 ion channel binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0002028 regulation of sodium ion transport
GO:0006713 glucocorticoid catabolic process
GO:0006886 intracellular protein transport
GO:0021762 substantia nigra development
GO:0042921 glucocorticoid receptor signaling pathway
GO:0045664 regulation of neuron differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0048167 regulation of synaptic plasticity
GO:0050774 negative regulation of dendrite morphogenesis
GO:0061024 membrane organization
GO:0086010 membrane depolarization during action potential
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:2000649 regulation of sodium ion transmembrane transporter activity

Cellular Component:
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0014704 intercalated disc
GO:0070062 extracellular exosome

-  Descriptions from all associated GenBank mRNAs
  X78138 - H.sapiens 14-3-3 eta subtype mRNA.
BC003047 - Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide, mRNA (cDNA clone MGC:675 IMAGE:3543571), complete cds.
S80794 - 14.3.3 eta chain=brain-specific tyrosine and tryptophan hydroxylase activator [human, cerebral cortex, mRNA, 1730 nt].
JD535498 - Sequence 516522 from Patent EP1572962.
AK312650 - Homo sapiens cDNA, FLJ93036, highly similar to Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenaseactivation protein, eta polypeptide (YWHAH), mRNA.
CR456612 - Homo sapiens YWHAH full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.YWHAH.V2).
AB385077 - Synthetic construct DNA, clone: pF1KB5280, Homo sapiens YWHAH gene for 14-3-3 protein eta, complete cds, without stop codon, in Flexi system.
L20422 - Human 14-3-3n protein mRNA, complete cds.
CU013496 - Homo sapiens YWHAH, mRNA (cDNA clone IMAGE:100000465), complete cds, without stop codon, in Gateway system.
CU013208 - Homo sapiens YWHAH, mRNA (cDNA clone IMAGE:100000561), complete cds, with stop codon, in Gateway system.
AK307750 - Homo sapiens cDNA, FLJ97698.
X57345 - H.sapiens mRNA for AS1 protein.
AY007132 - Homo sapiens clone CDABP0046 mRNA sequence.
JD020241 - Sequence 1265 from Patent EP1572962.
JD032835 - Sequence 13859 from Patent EP1572962.
JD026886 - Sequence 7910 from Patent EP1572962.
JD030838 - Sequence 11862 from Patent EP1572962.
JD042693 - Sequence 23717 from Patent EP1572962.
JD062403 - Sequence 43427 from Patent EP1572962.
JD420921 - Sequence 401945 from Patent EP1572962.
JD394072 - Sequence 375096 from Patent EP1572962.
JD521409 - Sequence 502433 from Patent EP1572962.
JD244943 - Sequence 225967 from Patent EP1572962.
JD106603 - Sequence 87627 from Patent EP1572962.
JD414196 - Sequence 395220 from Patent EP1572962.
JD369432 - Sequence 350456 from Patent EP1572962.
JD165373 - Sequence 146397 from Patent EP1572962.
L08439 - Human autonomously replicating sequence (ARS) mRNA.
JD504865 - Sequence 485889 from Patent EP1572962.
JD403569 - Sequence 384593 from Patent EP1572962.
JD248737 - Sequence 229761 from Patent EP1572962.

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

BioCarta from NCI Cancer Genome Anatomy Project
h_cdc25Pathway - cdc25 and chk1 Regulatory Pathway in response to DNA damage
h_aktPathway - AKT Signaling Pathway
h_hdacPathway - Control of skeletal myogenesis by HDAC & calcium/calmodulin-dependent kinase (CaMK)
h_pgc1aPathway - Regulation of PGC-1a
h_MITRPathway - Signal Dependent Regulation of Myogenesis by Corepressor MITR
h_rbPathway - RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage
h_achPathway - Role of nicotinic acetylcholine receptors in the regulation of apoptosis
h_g2Pathway - Cell Cycle: G2/M Checkpoint
h_badPathway - Regulation of BAD phosphorylation
h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation
h_plk3Pathway - Regulation of cell cycle progression by Plk3

Reactome (by CSHL, EBI, and GO)

Protein Q04917 (Reactome details) participates in the following event(s):

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-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-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-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-162582 Signal Transduction
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: 1433F_HUMAN, NM_003405, NP_003396, Q04917, YWHA1
UCSC ID: uc003alz.3
RefSeq Accession: NM_003405
Protein: Q04917 (aka 1433F_HUMAN or 143F_HUMAN)
CCDS: CCDS13901.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_003405.3
exon count: 2CDS single in 3' UTR: no RNA size: 1807
ORF size: 741CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1682.00frame shift in genome: no % Coverage: 99.23
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.